louis p. dehner . m.d. - uscap · profe:ssor of lj\borator'i hi~ojctne & pa.tj-iolo

PEDIATRIC SURGICAL PATHOLOGY

LOUIS P. DEHNER . M.D.

SATURDAY, SEPTEMBER 11 , 1976

THE KASS~ ACAOE~V Of M[OICI N[ G~ROEN CITY, HE~ YORK

PROCEEDINGS Of Tilt

SEVENTH ANNUAL SEMINAR

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PEDIATRIC SURGICAL PATHOLOGY

LOUIS P. DEHNER . M.D.

PROFE:SSOR OF LJ\BORATOR'i HI~OJCtNE & PA.TJ-IOLO

DIAGNOSES PAGE

CASE 1. TERATOMA , IMMATURE (BIOLOGIC POTENTIAL UNDETERHINANT) WITH 1 SUBSEQUENT MATURATION.

CASE 2. MATURE, SOLID TERATOMA WITH GLIOHATOSIS PERITONEI. 2

CASE 3. CYSTIC ADENOMATOID MALFOR11ATION 5

CASE 4. PLAS~IA CELL GRANULOMA (INFIJU.lJ.!ATORY PSEUDO'ItWIJR) 8

CASE 5 . ENTERIC DUPLICATION (FOREGUT DUPLICATION, MEDIASTINAL DORSAL ENTERIC SYTS ) 10

CASE 6 . MULTILOCULAR CYSTIC KIDNEY (MULTICYSTIC NEPHROMA) 11

CASE 7. MESOBLASTIC NEPHROMA (FETAL IIA~IA.RTOMA OF KIDNEY) 12

C. liSE e. WIUIS' TU~IOR 14

CASE 9. BILIARY CIRRHOSIS SECONDARY TO EXTRAHEPATIC BILIARY ATRESIA 15

CASE· 10 . REYE 'S SYNDROHE VARIANT(?) WITH SUBMASSIVE NECROSIS 18

CASE 11. NECROTIZING ENTEROCOLITIS (NEC) OF INFANCY 19

CASE 12. HISTIOCYTOSIS, MALIGNANT

CASE 13. ~IALIGNANT LYMPHOMA, POORLY DIFFERENTIATED LYMPHOCYTIC (LYMPHOBLASTIC) TYPE

CASE 14. SYNOVIAL SARCOMA

CASE 15. ALVEOLAR RHABDOMYOSARCOMA

CASE 16. SKELETAL HEMANGIOMA

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Case I: Soft tissue, neck (cervicothyroid) -Teratoma, immature (biologic potentia 1 undetenni nant) ~1fth subsequent ma tura ti on.

There is no more appropriate ar ea of pediatric pathology to begin a seminar than wi t h a discussion of the teratoma, an embryologic neoplasm if there 1·1as ever a candidate. The teratoma qualifies ful ly as an example in the words of Ruppert Willis as the "borderland of embryology and pathology". This case and the next have been selected as representatives of extra-gonadal and gonadal germ cell tumors in childhood. Each case illustrates some of the practical problems ~1hich confront the pathologist in terms of prog-nosticating fu ture behavior and secondly, the ponderabl e considerations of histogenesis .

Overal l, gonadal and extra-gonadal germ cell tumors do not constitut e a major probl em in the scheme of pediatric neopl asia. Rober t Hill er at t he Epidermiologic Branch of the NJtional Cancer Institute has been the best keeper and analyzer of the statistics and as you can see from a modification of his figures that germ cell tumors rank rather close to the bottom of the list (Table) . In 1973, Fraumeni and coworkers examined the epidemiologic features of teratomas in childhood and noted that female death rates ex-ceeded those of males, a reversal of the usual trend for malignancies in childhood. Sacrococcygeal teratomas in girls under 3 years of age accounted for many deaths .

. The first case involves a newborn who presented wi th a mass in the sub-mandibular regi on of the neck . An excision was performed and a yellowish-tan mass measuring 10 x 9 x 6 em., weighing 230 gm . was excised. On cut section, it had a multi cystic appearance with a mucoid-myxoid quality. Within a fe~1 weeks of the original excision, the mass had recurred with extension toward the esophagus and trachea. A second excision was performed. At the age of 1 l/2 years, there ~tas another recurrence and as far as I am aware, no metas-tases were identified.

I have had the opportunity of reviewing the sections from t he primary t umor and t he r ecurrences . The original sections show a t umor with a compl ex histologic appearance whi ch varies f rom tube-glandul ar f oci with an endo-dermal sinus patt ern, e1ongated glandul ar structures resembling primiti ve medullary canals, small nests of pigment-containing cel l s, cartilage and sheets of large pink cells resembling granular cells . Mucoid or gelatinous areas constitute a part of the background . Some differentiating somatic elements are noted. The structures composed of the hyperchromatic cells appear to be undergoing degeneration in many areas. Sections from the firs t recurrence are somewhat similar but I could recognize more mature elements, especially smooth muscle and nests of degenerating tumor were even more prominent. Focal infiltration of the submandibular gland was present. The most dramatic aspect of thi s case is represented in the second recurrence. At this time , the tumor has seemingly matured and represents a fu l ly mature and presumably benign teratoma.

This case il lustrates the fact that most germ cell tumors presenting in the newborn period are generally extra-gonadal and secondly, the histologic appearance may be deceptive in the prediction of future biologic behavior. In a review of the 4 major series of germ cell tumors in childhood (Ref. 1, 2, 3, 6), the cervicothyroid region accounted for 3 - 9% of all cases. Two series (Ref . 3, 6) had no examples. Over 90% of cervicothyroid teratomas present in infancy and 17% of cases have occurred in stillborns . Polyhydramnio has been documented in 20% of cases. These tumors ki ll as a result of the l ocal manifestations and according to Ha~1kins and Park (1972), there have been no examples of mal ignant teratomas of the neck in childhood but a few in adults. Roediger and coworkers (1974) have recently speculated about the hi stogenesis but I l ike to subscribe to the midline migration theory of germ cell s and their persistence and neoplastic transformation as an explanatio for extra-gonadal genn cell tumors. The events leading to maturation of the teratoma in this patient are Mt well understood but the work of Leroy Stevens (Ref. 9) with the testicular teratoma in mouse strain 129 has shed considerable light on the biology of these tumors.

References

1. Bale, P .~1., et al. Teratomas in childhood. Pathology 7:209, 1975. 2. Berry, C.L., et al . Teratomata in infancy and childhood: a review of

g1 cases. J . Pathol. 98:241, 1969 . 3. Carney, J.A., et al. Teratomas in chi ldren: clinical and pathological

aspects . J . Pediatr. Surg. 7:271, 1972. · 4: Dehner, L.P. Intrarenal teratoma occurr ing in infancy: rep9rt of

a case with discussion of extragonadal germ cel l tumors in infancy. J. Pediatr . Surg. 8:369, 1973.

5. Fraumeni, J.F., et al . Teratomas in children : epidemiol ogic features. J . Nat. Cancer Inst. 51:1425, 1973.

6. Hawkins, 0.8 . and Park, R. Teratoma of the pharynx and neck. Ann . Otol . Rhinal. Laryngo1. 81:848, 1972.

7. Mahour, G.H., et al. Teratomas in infancy and childhood: experience with 81 cases. Surgery 76:309, Jg74 .

8. Roediger , H.E. , et al. Histogenesis of benign cervical teratomas. Tera-tology 10:11 1, 1974.

9. Stevens , L.C. The biology of teratomas , Adv. Norphogenesis 6: 1, 1967. 10. Stone, H.H., et al. Teratomas of the neck. Am. J . Dis. Child. 113:222,

1967. 11. Young, J. L., Jr. and Mil l er, R.W . Incidence of mal ignant tumors in U.S.

chi ldren. J. Pediatr . 86:254, 1975.

Case 2: Ovary, oophorectomy- t~ature, sol id teratoma with gl iomatosis peritone

In a 3-year-old child 1~ith a large abdominal mass sh01~ing calcification by X-ray, the most common diagnosis is neurobl astoma . The catecholamine levels were normal but 1~e have seen a small percentage of biochemically inactive neuroblastomas . An exploratory laparotomy was performed and multilobular ad-nexal mass measuring 15 x 14 x 12 em . , ~1eighing 1225 gm. ~1as excised. The surface of the tumor was smooth ~lith some fresh hemorrhage. There ~1ere some

capsular adhesions and attached omental fat. The cut surface was mainly solid but a fe~1, small cystic areas ~1ere noted. In addition to the large solid tumor, the· peritoneum was diffusely studded with t iny white nodules measuring 1-3 mm. Several of these nodules were biopsied.

Multi ple · sections were examined from this ovarian neoplasm and those used in the seminar are representative of the tumor. Almost without ex-cepti-on, the morphologi c elements are somatic rather than embryonic o'r extr,f-embryonic and there is evidence of maturation. The predominant tissue type is mature neuroepithelium. A rare cluster of small, dark cells resembling neuroolasts and an elongated immature. medullary canal are noted. Other elements included skin with appendages, respiratory mucosa, cartilage, mature ganglia, smooth muscle, fat and bone. Although you did not have a section of one of the peritoneal nodules, they were composed elusively of mature neuroglia surrounded by a'dense chronic infla111natory reaction. Thes.e implants are characteristic of so- cal led "gliomatosis peritonei. "

Approximately 20-35% of al l germ cell tumors in childhood originate in the ovary and one-half or mor·e of these ovarian neoplasms are mature cystic teratomas. In a review of 353 tumors of the ovary at the Armed Forces Institute of Pathology, 58% of neoplasms were derived from germ cells followed tiy surface epithelium (19%) and gonadal stroma (18%)(Ref. 8). It

' has been estimated that 10-15% of ovarian germ cell tumors in childhood are mal ignant .

Tne solid teratoma of the ovar.y is rare neoplasm among the germ cell tumors. Thurlbeck and Scully (Ref. H ) and even earlier, Peterson (Ref . 9) described the clinical and pathologic features of the solid teratoma. As is true for most germ cell tumors of the ovary, the patients are ·usually .diagnosed during the first three decades of 1 ife and an abdominal mass is the most common mode of presentation . Most solid teratomas are unilateral (95%} and the characterization of the tumor as "sol id" is somewhat misleading since mul t icystic areas are invariably present. A system of histologic grading was devised by Thurlbeck and Scul ly (Ref. 11) in an attempt to pre-dict future clinical behavior. Their system is as follows:

HISTOLOGIC GRADING OF SOLID TERATONAS OF THE OVARY (T~urlbeck-Scully, 1960)

Grade 0 All cells ~Jell differentiated. Grade 1 Ce 11 s 1~e 11-di fferent i a ted except in rare

small foc i of embrypnal t issue. Grade 2 Moderate quantit ies ' of embryonal tissue

present; cel l s show atypicality and mitotic activity.

Grade 3 Large quantities of embryonal tissue present; cell shows atypicality and mitotic activity

Two recent studies by Beilby and Parkinson (Ref. 2) and Norris and coworkers (Ref. 7} have applied this system of histologic grading to such tumors. In 16 of the 20 cases in one series (Ref. 2). the authors concluded that the determination of the amount of immature embryonic tissue was un-reliable. · A more important feature ~1as the presence o·f the endodermal sinus

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pattern in the tumor 1~hi ch 1~as indicative of a poor prognos 1 s. Norris and coworkers (Ref. 7) in an exa'mination of 58 iiMlature ovariao teratomas were more optimistic about the application of the Thurlbeck-Scully system but also felt that the size of the tumor and the clinical stage vtere other significant prognostic factors. Based upon the Thurlbeck-Scully system, the tumor in the seminar straddles bet1~een grade 0-l since there are small neuroblastic-appearing cells. I have not found that the presence of neuroblasts in a germ cell tumor sho.uld be viewed with any great concern, however, the occurrence of the elongated, primitive medullary canals in a teratoma is another story. These stru,ctures and the "gl omerul,oid" or Schiller-Duval bodies are indicative of malignancy .

In any other context when the peritoneum is seeded vtith tumor implants as this child had at the time of surgery, a poor prognosis would be undis-puted. The un ique situation of so-called "gliomatosis peritonei" sets it apart. Thurlbeck and Scully (Ref. 11) documented this phenomenon in one of their patients (Case 3) who was still alive 26 years later with omental and peritoneal metastases vthich vtere composed solely of mature glial tissue. Since that report, Robboy and Scully (Ref. 10) analyzed 12 cases and nearly all re-presented examples of grade 0 sol id teratoma . In 10 of the 12 cases, a tear and/or omental adhesions vtere noted o.n the surface of the tumor. )he follow-up ranged from 9 months to 38 years . The 38-year foll01~-up was the original patient reported by Thur'lbeck and Scul l y. Additi'onal cases of gliomatosis peritonei since the 1970 report have been published by Favara and Franciosi

.(Ref. 3), Livaditis and coworkers (Ref. 5) and Nogales and Oliva (Ref. 6).

References

1. Abell, M.R., et al. Ovarian neoplasms in childhood and adolescence . 1. Tumors of germ ce 11 origin. Am . J. Obstet. Gyneco 1. 92: 1059, 1965 . 2. Beilby, J.O.H. and Parkinson, C. ' Features of prognostic significance in solid ovarian teratoma. Cancer 36:2147, 1975. 3. Favara, B.E. and Franciosi, R.A. Ovarian teratoma, and neuroglial implant's in the peritoneum. Cancer 31:678, 1973. 4. Fox, H. and langley, F.A. Tumours of the ovary, Chicago, 1976, Year Book Medi~al Publisher, Inc., p. 211-226. 5. Livaditis, A., et al. Ovarian teratoma in an infant with peritoneal dissemination of glial tissue. Z. Kinderchir. 12:249, 1973. 6. Nogales, F.F., Jr. and Oliva, H.A. Peritoneal gliomatosis produced by ovarian teratnmas . Obstet. Gynecol . 43:915, 1974 . 7. Norris, H.J., et al. Immature (malignant) teratoma of the ovary. A clinical and pathologic study of 58 cases. Cancer 37:2359, 1976. B. Norris, H.J. and Jensen, R.D. Relative frequency of ovarian neoplasms in c!ii 1 dren and adolescents. Cancer 30': 713, 1972. 9. Peterson, W.F. Solid, histologically benign teratomas of the ovary. A re port of four cases and review of the literature. Am. J. Obstet. Gynecol. 72: 1094' 1956. 10. Robboy, S.J. and Scully, R.E. Ovarian t eratoma with glial implants on the peritoneum: an analysis of 12 cases. Human Pathol. 1:643, 1970. ll. Thurl beck, ~/.M. and Scully, R.E. Solid ter.atoma of the ovary. A ~:linicopathologic analysis of 9 c~ses. Cancer 13:804, 1960.

Case 3 - Lung - Cystic adenomat oid malformation

The causes of respiratory difficul ties in the neonatal period are most conveniently divided into surgical and non-surgical eti9logies (Ref. 5, 14} . Although the anatomic material from the current case was obtained at autopsy, the uncommon cystic adenomatoid malformation of the lung is well-known cause of respiratory distress in the newborn. The chi ld in this seminar weighed 6 pounds, 2 ounces at birth and was the product of a pregnancy complicated by prolonged rupture of membranes (18-20 hours). At delivery, the infant was flaccid and cyanotic. She required resuscitative efforts and the respirations were characteri zed as grunting with subcostal retractions. The breath sounds were poor to absent and a chest film revealed non-aeration of the left lung and almost complete consolidation of the right lung with one large emphysematous bleb. As far as could be determined, the tracheobronchial tree was patent . A reasonable clinical diagnosis may have been congenital or perinatal pneumonia secondary to the prolonged rupture of membranes (Ref. 1). Beyond a period of 36 hours with ruptured membranes, the risk of pneumonia climbs precipi tously. Meconium aspiration, di ffuse pulmonary hemorrhage, neonatal atelectasis and with the emphysematous bleb, congenital lobar emphysema were other possibilities. Hyalin membrane disease is not likely in the light of the time interval and the roentgenograph; c findings.

The patient died at 8 hours . At autopsy, the right lung weighed 52 gm. and the left, 26 gm. With the exception of the right lower lobe, the remaining lobes were described. as atelectatic. The right lower lobe was mottled, dark reddi sh to grey and on cut secti on, it had a soft, fleshy appearance with numerous cysts measuring from 0.3 - 1.8 em. in diameter. Histologically, the sections from the right lower lobe revealed rather uniform appearing epithelial-lined spaces . There were some cystical ly dilated structures and in occasional foci, the lining cells were columnar and contained cytoplasmic mucin. Most epithelial cells were cuboidal. Fibrous septa containing a prominent vascular component were also present. Throughout the various sections, bronchial car-tilage was obviously absent. Differentiated alveolar spaces were extremely un-common . Thi s case ful fills, for the most part, the 5 criteria which Bai n (Ref. 3) considered necessary for the diagnosi s: 1) absence of bronchial cartilage; 2) absence of bronchial tubular glands; 3) presence of tall columnar mucinous epithel ium; 4) overproduction of terminal bronchiol ar structures without alveolar differentiation except in subpleural areas; and 5) massive enlargement of the affected lobe displacing other thoracic structures.

Malformations of the lung have been classified in various ways. Potter and Craig (Ref. 13} have divided pulmonary malformations into 4 basic categories (Table 1) and this child's problem is l isted under the heading of "abnormal composition". Congenital cysts and cystic malformations of the lung have been the source of much confusion in terms of basic pathogenesis and nomenclature. Levi ne and coworkers (Ref. 9) as part of an overall classificat ion of pulmonary anomal ies have devised one workable categorization (Table 2).

In addition to respiratory difficulties in the neonatal period, fetal hydrops-anasarca and polyhydraminios are other associated findings (Ref. 8, 12) . The respiratory distress that a newborn experiences increases over time as air

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becomes entrapped withi n the cys ts. It shoul d be remember ed that t here is no cart ilaginous support to the major ·air-ways. Eventuall y, there is shi ft of the medias t inum. There have been cases t hat have had a delayed presen-tation after a period of weeks or mon t hs 1~hen persistent or repeated pulmonary infections were present .

Mos t cli nicopathologic studi es of the cystic adenomatoid malformation have invol ved no more than 1-3 cases , however, f.!adewell and cm~orkers (Ref . 10) have examined the features of 31 cases a t the Armed Forces Insti t ute of Patho1qgy, fl.s in our case, the l 01·1er lobes ~1ere princi pally affected and most mal formations have a macroscopic cystic appearance . Demp~ter (Ref. 6) and Van Dijk and \~a genvoort (Ref. 15) have reported a sol id vari ant. Rad i ographically, a persistent soft ti ssue density 1~as noted in the l ung.

An imnted iate l obectomy is necessary if a chi l d is going to survive thi s rna l formation (Ref. 7) . ·

References

1 .. Askin, F.B. Lungs (Chapter 19) in Pathology of Infancy and Childhood, Second editi on, Kissane, J.t•1., St. Loui s·, THe C. V. ~1osby Company, 1975, pp. 471 -532 .

2. As l am, P.A., et al . Congeni t al cystic adenomatoid malformation ~lith ana-sarca . J.A.M .A. 212:622, 1970.

3. Bain, G.O. Congenital adenomatoi d mal formation of ~he lung . Ois. Chest 36:430, 1959.

4 . Craig, J .M., et al . Congenital cysti c adenomatoid ma l f ormation of the l ung in ihfanls, Am. J. Roentgenol . Radium Ther . Nucl. Hed. 76~516, 1956.

5. Dehner, L.P . · Pediatric surgica l pathol ogy, St. Louis, The C.V. Mosby, Company, ]975, p. 198-205.

6. Dempster, A.G. Adenomatoid hama rtoma of the lung in a neonate. J. Clin. Pathol. 22:401, 1969 .

7. Halloran, L.G . , et al. Congenita l cystic adenomatoid mal formation of the 1 ung. A surgi caJ emergency. Arch. Surg. 104: 715, 1972.

8 . Kohler, H.G. and Rymer, B.A. Congenital cystic malformation of the lung and its re·lation to hydramni os . J. Obstet. Gynaecol . Br . Commonweal t h 80: 130' 1973.

9. levine,. ~1. , et al. Congeni tal pulmonary anomal ies and related thoracic conditions. , Report of subcommittee on congenital anomal ies of the lungs . Ois. Chest 49:441, 1966.

10. ~1adewell , J.E., et a l. Cysti c; adenomatoi d ma l formation of the lung. 1•10rl?h-ol ogic ana.lys is. Am. J . Roentgenol . Radium Ther. Nucl. 11ed. 124:436, 1975.

11. Merenstein, G. B. Congenital cystic adenomatoid malformation of the lung . Report of a case and review of the l iterature. Am. J. Dis. Child . ll8: 772, 1969.

12. Mi chal sen, H. Corigenjtal cys t ic adenomatoi·d malformation of the lung. Acta Paediatr . Scand . 63:793, 1974.

13 . Potter, E.L . and Crai g, J.~1. Pathol ogy of the fe tus and t he i nfant , Third edition, Chicago, Year Book f•led ical Publ isher, Inc., 19.75, p. 274-316.

14. Schapiro, R.l. and Evans, E.T . Surgical disorders causing_neonatal respiratory di stress. Am. J. Roentgenol . Rad i um Ther. Nucl. Med. 11 4 : 305' 1972.

15. Van Dij k, C. and Waqenvoort, C.A. matoid malformation of the lung.

The various t .vpes of congenita 1 adeno-J . Pathol. 110:131, 1973.

TABLE I: PULMONARY MALFORMATIONS

(Potter and Craig, 1975)

I. Abnormal size ~· Primary hypoplasia

1. Bilateral (rare, acephauls} 2. Unilateral (70% left, M:F/2:1, T-e fistula)

B. Secondary hypoplasia 1. Diaphragmatic hernia 2. Craniospinorachischis4s (anencephaly} 3. Renal agenesis, occ. infantile polycystic kidneys

II. Abnormal position III. Abhormal lobation

1. Sequestration IV. Abnormal composition

1. Cystic adenomatoid malformation 2. Solitary cysts 3. Congenital pulmonary lympha·ngectasia (Laurence) . 4. Heterotopic tissue

Tab 1 e It: CONGENITAL CYSTS AND CYSTIC MALFORHATIONS OF THE LUNG (Levine, et al., 1966)

I. Congenital cysts A. Solitary

1. Asymptomatic I

2. Tension and communicating B. t•1ultiple cysts C. ·Cystic bronchiectasi-s

II. , Cystic malformations A. Solitary cysts B. ~1ultiple cysts C. Cystic sequestration D. Cystic adenornatoid rna 1 formation E. Diffuse cystic lymphangiectasis

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Case 4 - Lung - Plasma cell granuloma (inflammat ory pseudotumor)

When t his 2-year-old chil d was admitted to t he University Hospi tals, there ~1as some confusion and uncertainty about t he clinical diagnosis. The mass in the chest 1~as initially interpreted as being located in the anterior medi astinum and there ~1as a question of leukemia . It was finally resolved before surgery that leukemia 1~as not present. At t horacotomy, the mass re-sided in the right upper lobe and a wedge resection 1~as performed.

Grossly, t he mass was contained wi t hin the pulmonary parenchyma and had a well-cricumscribed lobular contour. It was firm and measured approxi -mately 3.5 x 3.5 x 3.0 em. A gritty consistency was noted on cut surface . The tumor had a yellowish-grey color, a sl i ghtly-whorled appearance and focal stippled calcification. A frozen section had been performed and a diagnosis of an inflammatory process was made. Histological ly, the pre-dominant microscopic elements were mature fibrous ti ssue a~d sheets and aggregates of mature plasma cells . Entrapped, residual respiratory structures were present ~1it hin the mass. A rare binucleated plasma cell and occasional Russell bodies were i dentified. The focus of dystrophi c calcificat ion was also con firmed . Although the mass appeared ~/ell -demarcated in the gross examination, the inflammation and fibrosis blended into the adjacent paren-chyma. It has been 6 months since surgery and the child is doing well.

Tumor and tumor-like disorders of the lung are relatively uncommon in childhood as attested by one's persona 1 exper i ence and the paucity of literature (Ref. 9). Individual case repor ts of pulmonary t umors in chi ldren serve as testimonials to the rari ty of lung neoplasms in this age group. Of the primary mal ignant tumors , the carcinoid type of "bronchial adenoma" is the most common neoplasrn of the lung in childhood. Hellons and coworkers (Ref. 11) reported 2 cases and collected 56 from the literature. The usual varieties of pulmonary carcinoma encountered in adul ts are among the rarest of pediatric neoplasms. Niitu and coworkers (Ref. 6) have revi ewed the ex-perience in Japan and the other count ries of the worl d. In our own institution, solitary or multi pl e, small peripheral metastatic lesions to the l ungs are the commonest mal ignant tumors wh ich we have a chance to examine as surgical specimens . Osteosarcoma and Wilms' tumor together account for 90% of all such cases. Pulmonary biopsies from children with malignant disease are not at all infrequent when the diagnosis of an opportunistic infection is being considered . In most cases, the diagnosis of Pneumocystis carinii pneu-monia is being at t empted. His tiocytosi s X (d if ferent iated his t iocytosis), mali gnant histiocytosi s and Ewing' s tumor have been the other pathologic di s-orders for which pulmonary biopsy or resection has been attempt ed in the past .2 years at the Universi ty Hospi tal.

The plasma cell granuloma certainly qualifi es as a tumor- like process and, in fact, "inflammatory pseudotumor" has been a term used in the past. Bahodori and Liebo1~ (Ref. 2) prefer t he appellation of plasma cell granulomas. Hist iocytoma, xanthogranuloma and xanthoma are just some of the other less

·f requently used synonyms. Thi s ci rcumscribed mass-l esion i s general ly lo-cated in the peripheral lung f ields, less frequently as an endobronchial mass. In Bahadori and liebow's experience, over one-half of 40 patients that they

studied ~~ere initially asymptomatic. Those with symptoms had a cough, short-ness of breath or hemoptysis. Approximately 27% of the patients in the latter study were 10 years of age or younger at diagnosis and one-third were less than 20 years. Pearl (Ref. 7, 8) has descrioed t.he clinical and r.oentgenographic features of this lesion under the heading of "po$tinflammatory pseudotumor" in a group of children. On~ of her cases had a respiratory infection and developed a circumscribed mass which was followed by a second lesion that extended into the mediastinum and encroached upon the right inferior pulmonary vein •

. The plasma celi granuloma has a predilection for the lower lobe, measures from 1 - 12 em. in greatest diameter and nas the firm, greyish to yellowish-brown appearance that the mass in the seminar had. His topathologically, some variations in cel l types may be apparent. For instance, histiocytes, lympho-cytes, mast cells and eosinophils are also present, especi~lly the foamy hi~tiocytes. Necrosis was evident in only 3 of the 40 cases in the Bahadori and Liebow series. Limited resection is generally curative (Ref . . 5, 10).

Most cases have not been historically associ a ted with a preceding pulmonary infection. Ackerman and coworkers (Ref. 1) dre~1 attention to the similarities of localized organizing pneumonia to carcinoma of the lung. Microbiologic exami~ation of the plasma cell granuloma has been unproductive in terms of identifying a pathogen. There have been 2 recent ul trastructura 1 studi·es (Ref. 3, 4) which have further defined the morphology but have shed very little light on the pathogenesis.

References

1.

2.

3.

4.

Acl

Case 5 - Mediastinum - Enteric duplication (foregut duplication, mediastinal dorsal enteric cyst)

This case is illustrative of 2 problems in pediatric surgery and surgical pathology and those being a mediastinal mass in a child and gastrointes tinal duplication. The patient was 5 years old when first seen with symptoms and s i gns of pneumonia wh i ch was treated with antibioti cs . We a.re not told ~1hether a chest x-ray was taken at that initial present ation but 2 months l at er ~1hen he re-presented, a 5. 5 em. mass was no t ed i n the 1 eft retro-cardiac area. I t ~1as not i ndi cated whether an a i r-fl ui d l evel was associ ated 11ith the l esi on nor if the vertebra 1 bodi es 1vere norma 1 .

The cyst was grossly unilocular and 1·1as somewhat l arger than the dimensi ons from the x-ray. 1·1icroscopi cally, t he l ining epithel ium has been ulcerated in many foci and replaced by inflammatory ce~ls, granulation tissue and fibrosis . Where t he surface is intact, it ranges from stratified cuboidal to clearly gastric in cy In these latter areas, a muscularis is identified. Aggregates of lymphocytes are present in the submucosa . There was no evidence of ciliated stratified epithelium nor isl ands of cartilage. If these tissues are noted in a duplication cyst, ·then the diagnosis is that of a "bronchopulmonary foregut malformat ion" .

A survey of 283 tumor and tumorli ke disorders of the mediastinum from 4 pediatri c series reveal ed t hat approximately 8% of such lesions were diagnosed as gastroenteric dup l icati ons (Ref . 3). Bronchogeni c cysts represented 3% of t he combi ned ser i es . The l argest si ngl e gr oup of neoplasms of the mediastinum i n chi 1 dhood was t he neurogeni c category ( 35%), fo 11 owed by the germ ce 11 t umors (14%) and mal ign9nt lymphomas (14%}.

The enteric cyst of the medi astinum is one of the tlvo types of f or egut cysts, the other being the bronchogenic cyst (Ref . 9} . r~ost dupl i cations of the intestin tract are located in t he small intestine, particularl y in the region of the ileum (Ref. 5-7) . About 20% of duplications occur above the diaphr agm and most are associated with the esophagus or paraesophageal (Ref. 11) . Thoracic duplications are usually diagnosed in the first year of life but obviously our patient managed to escape detection. Respiratory distress due to tracheal and/or pul monary com-pression and dysphagia are some of the more frequent presenting features. A unique presentation has been reported ~1ith the dupl i cation cyst of the mediastinum l ined with gastric mucosa (Ref. 2}. Gross ulceration and pepti c digestion of adjacent anatomic struct ures ~li th pul111onary suppuration and/or hemorrhage ar e the major fi ndi ngs. Anomal i es of t he vertebrae (spl it notochord system) are ot he r related abnormal iti es es peciall y when the dupl ication ori ginates in the med ia-stinum (Ref. 12). The embryo 1 ogi c aspects of the dup 1 i cati on have been rev i e1~ed by Bremer (Ref. 1 ), Kissane (Ref. 9} and Favara and coworkers (Ref . 4}. A vas-cular theory is proposed by the l atter authors .

Anatomically , the dupliccrtion has a cystic appearance in this case or alternatively, it is tubular. In the abdomen, most duplications are contained within the leaves of t he mesentery and more often than not there is no communica-tion wi th the normal l umen of the bowel. The mucosal lining of the duplication does not ah1ays correspond to that of the adjacent bowel . A complete muscular tunic i s identified in those cases in which the separation is complete between the bo1~el and the dupl ication.

The "bronchopulmonary foregut malformation" (BPFt-1) is worthy of a few comments since it represents a bridging anomaly between the respiratory-re-lated and gut-related defects (Ref. 8) . By definition, the BPFM is a patent communication between accessory lung tissue and esophagus or stomach. In addition to intra- and extralobar sequestration with or without communication with the GI tract, the congenital esophageal diverticulum and foregut mal-formations are part of the embryopathogenetic spectrum.

References

1. Bremer, ,J. L. Diverticul-a and dupli cations of the intesti nal tract . Arch. Pathol. 38:132, 1944.

2. Chital e , A.R . Gastric cyst of the mediastinum. A distinct cl inicopathologic entity. J . Pediatr . 76:104, 1969.

3. Dehner, L.P. Pediatric Surgical Pathology, St. Louis, The C. V. ~losby, CO. 1975, p.l83-1 86. . •

4. Favara, B. E. , et al. Enteric duplications. Thirty-seven cases: a vascular theory of pathogenesis. Am. J . Dis . Chi ld. 122:501, 1971.

5. Franklin, E.A., Jr., Gastrointestinal radiology in pediatrics, Hagersto1~n. Harper and Ro1~. 1975, p. 37-40.

6. Grosfield, J .L., et al. Enteric duplications in infancy and childhood: an 18-year review. Ann . Surg. 172:83, 1970.

7. Gross, R.E., et al. Duplications of the alimentary tract. Pediatrics 9: 44g, 1957.

8. Heithoff, K. B. , et al. Bronchopulmonary foregut malformati.ons . A unifying etiological concept. Am. J. Roentgenol . Rad ium Ther. Nucl. ~led. 126:46, 1976.

9. Kissane, J . M. Pathologv of infa ncy and ch1ldhood. Second ed i tion, St. Louis, The c. v. ~losby, Co., 1975, p. 157-161.

10. LeRoux, B. T. Intrathoracic duplication of the foregut. Thorax 17:357, 1962 . 1 1. Reed , J. C. and Sobonya, R. E. ~1orpho 1 ogi c ana lysis of foregu t cysts in the

thorax. Am. J. Roentgenol. Radium. Ther. Nucl . Hed. 120:851, 1974. 12. Rhaney, K. and Barclay, G.P.T. Enterogenous cysts and congenital diverticula

of the a 1 imentary cana~ 1·1ith abnorma 1 i ties of the vertebral column and spina 1 cord. ,J. Pa tho 1 . Bacteri o 1 . 77:457, 1959.

Case 6 - Kidney - Multilocular cystic kidney (multicystic n~phroma)

The multicystic mass in the kidney of this 1-year-old child presents the differentiated diagnostic problem of "polycystic lesions" of the kidney in children (Ref. 5, 6). There are ·certain features of the gross specimen in this case which should give us some direction in the correct diagnosis. Although the kidney is quite l arge and obviously conta ins a mass, the overal l contour and outline of the organ is reta ined. This distinction i s made because t he so-called mul ticystic dysplastjc kidney has an extremely irregular outl ine and lacks the reniform appearance. The cysts are i rregular in size whereas in the multilocular cystic kidney, the individual cvsts are more or less the same size. ThesP. cysts do not interconnect with each other nor l•!i th the rena 1 pe 1 vis . 'Another finding in the gross specimen in the latter lesion is circumscription and apparent encapsulation of the mass from the compressed but otherwise normal rim of kidney. The "total" or complete multicystic dysplasia fails to have any identifiable normal renal parenchyma (Ref. 3, 7, 8) . Fi nally, the pedicle should be carefully examined since the renal vessels and ureter are quite attenuated and in the case of the ureter, it is atretic or absent in the multicystic dysplastic kidney. These structures are generally normal in the mul ti locular cystic kidney.

Microscopical ly , the multilocular cystic kidney is composed of cysts and fibrous septa 1~ith a few bundles of smooth muscl e (Ref. 4} . Some cysts are lined by a 1 0\'1 cuboida 1 epithe 1 i urn 1·1hereas others do not have a 1 ini ng epithe 1 i urn. The septa may contain atrophic glomeruli or tubules. Nei ther normal or dys-plastic nephron el ements are present in the septa. On occasion, imma ture mes-enchyme i s identifi ed wi thin these septa and in fact , nodules l•lith the features of ~lilms ' t umor have been noted. The question is then of a Wilms' tumor ar i sing in a multi locul ar cystic kidney. A contrasting microscopic appearance is present in the multicystic dyspl ast ic kidney in which immat ure glomerul i, tubules, mes-enchymal and even cart i l age are the typi ca 1 f indings. These various st ruc tures occur as sol id nests or t hey are located within the septa.

The histogenesi s of the mul t il ocular cystic kidney remains a disputed point i n that some consider i t a developmental anomaly and tohers , a neoplasm (mul t i-cystic nephroma }. Bal dauf and Schulz (Ref. l} have recently reviewed t he approximately 70 cases in the 1 iterature of multilocular cystic kidney. About half the cases have been described in childhood and the mean age has been 17 months . As expected, Wilms' tumor ~1as the most frequent pre-operative diagnosis. None of the cases to date with Wilms ' tumor occurring in a mul t ilocular cystic kidney have metastati zed (Ref. 2} .

References

1. Baldauf, M. C. and Schulz , D.M . Multilocul ar cyst of the kidney. Report oft ca ses with revi e1~ of the l i terature . Am. J . Cl i n. rathol . 65:93 , 1976.

2. Bennington, J . l. and Beck1•1i t h, J . B. Tumors of the kidney, rena 1 pe 1 vi s, and ureter. At l as of Tumor Pathol ogy, Armed Forces Insti tute of Pathology, 1975, p. 81-85. .

3. Bernst ein, J. The morphogenes i s of renal parenchymal maldevelopment (renal dysplasi a}, Pediatr . Clin. North Am. 18:395, 1971 .

4. Dainko , E.A. , · et al . Multilocular cysts of the kidney in chi ldren . Report of a case and revi ew of the literature. J . Pedi atr . 63:249, 1963.

5. Gleason, D.C., et al . Cystic disease of the kidneys in children . Am. J. Roentgenol. Radium Ther. Nucl. Med. 100:135, 1967.

6. Kissane, J .M. Pathology of infancy and childhood. second edition. St . Louis, The C. V. 1·1osby , Co . , 1975, p. 582-593 .

7. NeMnan, L. et al. Unil ateral tota l rena l dysplasia in ch i ldren. Am J . Roentgenol. Radium Ther. Nucl . ~led. 116: 778 , 1972 .

8. Risdon, R.A., et al . Renal hypopl as ia and dyspl asia: a radi ol ogical and pathological c.orrel ation. Pedi atr. Radiol . 3:213, 1975 .

Case 7 - Ki dney - Mesobl as t ic nephroma (fe ta l hamartoma of kidney) ~

There were probably fe~1 among t he many exami ners of this t umor that did not r~cognize thi s mesenchymal neoplasm of the kidney as a mesobl as t ic nephroma . In the past, this t umor 1~as diagnosed as a congenita 1 or neonata 1 Wilms' tumor. tlo only a nephrectomy but irradiation therapy 1·1ould have been the treatment . ,

Bolande has been much of the credi t for his clinical and pathologic des-cr ipt ion of this tumor in 1967 with a report of 8 cases (Ref. 4}. With few

exceptions, t he ·mesobl astic nephroma presents as an abdominal mass in the neo-nata l period . The gross features of t he tumor are ra ther typical in that mos t of t he renal par.enchy,ma has been replaced by a circumscribed but non-encapsulated greyi s h-wh ite to yell owi sh-grey mass. A whor l ed to trabecula ted appearance is ·characteris t i c of the cut surface and the features are very s imil ar to t he ut erine leiomyoma. The lobul ated, myxoid character of the Wilms' t umor i s absent as. well as hemorrhage and necros is i n most cases . Al t hough the renal capsul e is intact in the majority of mesoblastic nephromas, we have seen ex-tension t hrough t he capsul e and involvement of the per i r ena l sof t tissues. A l ocal recurrence is certainly possibl e and has been reported but o,te have re-commended watchfu l 1~ai t i ng rat her than i111nedi ate re-exp 1 oration or i r radi at ion therap,.Y . To t he best of our knowl edge· and o thers, all cases to date have been unilateral (Ref . 2, 3 , 5, 10).

Hi sto-l ogically, the mesobl astic nephroma h_ils a rather monotonous morphol ogy i n that t he t umor shows a predominantly spi ndle cell, interl ac i ng pa t t e rn . The

· tumor cells resembl e smooth muscle cells. Mitot i c activi ty may be abundant and some areas of the tumor may show not only i ncreased mi toses but the cel ls are di stinctly a t ypi cal and hyperchromat i c. Bizarre cellular forms are extremely unusual. rso l ated glomerul i and tubules are present among the spindle cells but .t hese are thought by most to represent entrapped normal str uc t ures. Small t ongues of spindle cell s ext end among the g l omerul i and t ubules at the periphery of the tumor. Dyspl astic tubules and is l ands of feta l carti l age have a l so been desc'ri bed in these tumors (Ref. 2, 5).

Tfie mesoblastic nephroma l ike the Wilms' tumor is thought to originat e f rom the metanephric blastema. Whether the spindle cell is a f ibroblast or smoot h muscle cell has been the subject of tissue cul ture and ul trastructura l s tudies withou t to t al resol ut ion of t he question (Ref. 7). Our moderator on t he basis of ultr:astructural examination ha-s proposed t hat the tumor i s deri ved from "secondary" mese liiC hyme which unlike the mesobl ast (primary mesenchyme) is in-capable of epi thel i al d i f ferentiation (Ref. 11) .

From the prognostic standpoi nt , nearly all cases to da.te have pursued a benign c l inica,l course. ·. The exception to this indolent behavior has been doc-umented i n case re ports (Ref. 8, 9) and Beckwith (Ref. 1 ) bas sounded a not e of caut ion about the " shades of grey" mesobl ast i c nephromas.

Refer.ences

1. Beckwith, J . B. t-lesenGhymal rena l neopl asms of infancy revisited . J. Pediatr. Surg. 9:803, 1974.

2. Bennington, J . L. and Beckwi th, J . B. Tumors of t he kidney, rena 1 pe 1 vis , and ur eter. Atlas of Tumor Patho l ogy, Armed Forces Tnstitute of Patho l ogy, 1g75, p. 79-81 . ;

3. ·sogdan, T. et al. Leiomyomatous hamartoma of the ki dney. Cancer 31:462, 1973'.

4. Bolande, R.P., et al . Congeni tal mesobl ast ic nephroma of infancy. A r epor t of eight cases and t he relationship to Hi1ms ' tumci r. Pediatrics 40:272, 1967.

5. Bo l ande, R. P. Congenital mes.ob l ast i

8. Joshi , V. V. et al . Congeni t al mesoblasti c nephroma of infancy: report of a case with unusual cl inical behavior . Am. J . Cl in . Pathol . 60: 811, 1973 .

9. Walker, 0. and Ri chard, G.A. Fetal hamartoma of the kidney: recurrence and death of a patient . J. Urol. 110: 352, 1973.

10 . Wigger , H. J . Fetal hamar toma of. kidney. A benign , symptomatic , congeni tal tumor , not a form of loilms' tumor. Am. J . Cl in. Pat hol . 51: 323, 1969.

11. Wigger , J . H. Fet al mesenchymal hamar toma of kidney. A t umor of secondary mesenchyme . Cancer 36: 1002, 1975.

Case 8- Kidney- Wi lms ' tumor

Al t hough thi s 18-year-ol d female defini ti onal ly does not fa ll into t he ped-iatri c age group (0-15 years), she has a rena l tumor wi th the features of a flilms' tumor that is moderate 1 y we 11-differenti a t ed . There have been scattered case report of Wil ms ' tumors in adul ts but t he hi st opathol ogy has often been di ff i tult to evalua i n some of these (Ref. 10). An interesting clinica l - l aboratory aspect of t his pati ent was the presence of polycythemia. As you no ted from the protocol , the pre-operative erythropoi et in l evel was within normal limi ts. A hemoqlobin determinat iOfl performed 1 month after surgery was 14 gm/dl. Erytftroooi etin-producing Hilms' tUJ!X)f have been reported in the past (Ref. 6,11). A nephrectomy was performed and a well-encapsulated tumor measuring 4.5 em. in qreatest diameter 1~as present in t he lower pole. There was no evidence that the tumor had extended beyond the caosule and t he blood vessels were grossly uninvolved.

Hi stologica ll y, the better di ffe renti ated areas of the tumor are composed of close 1 y packed immature or dyspl astic appearing tubules and di 1 a t ed s tructures with papillary tufts resembling embryonic glomeruli. Other fie l ds are character-i zed by dense sheets of small basophil i c tumor ce ll s wi thout differentiatinq features . At the peri phery and ~lith i n t he tumor, there are bands of hyalinized coll agen. Mul tiple calcospherul es or psammoma bodies are present within the cel lular porti on of the tumor and wi thin the hyalin bands. There is no evi dence of vascular invasion.

The initial question ~thich was oosed ~/Cis the hi sto!)athologic diagnosis of t he tumor . Some consi deration was qiven to the possibility of a renal cor tical adenoma of the "embryoni c type . " On t he basis of si ze alone, it was difficult t o reconci le the di agnos is of an adenoma since cor tical t umors in excess of 2-2. 5 em. are thought by ma ny to re!)resent carci nomas. The overall histology of a t umor composed of immature tubul es, glomerul i and mesenchyme must l ogi cal ly be interpreted as a nephroblastoma or Wilms' t umor regardless of t he age of the pati ent.

~

The subj ect of ~lilms' tumor i s one t hat has been extensive ly revie~ted from the cl i nical , pathologic and t herapeutic standooint over the past 25-30 years (Ref. 1,3,4,12). 14ore ·recently, t he l i t erature has emphas i zed the tre-mendous t herapeutic success which has occurred as a result of i rradiation and chemot hera"y (Ref . 4) . The- National Hilms' Tumor Study in this regard has been the model of cooperative studies (Ref. 2). A standardized syst em of staging has evolved from thi s study which int imately involves the pathologist and his evaluation of the extent of tumor. In the gross examination, the obser-vation of l~hether the capsule is intact is extremely imoortant and the presence or absence of gross vessel invasion (rare compared to renal cel l carcinoma). Histological ly, the differentiation of the tumor does appear to influence the prognosis but the point remains some~1hat controvers ial (Ref. 5,8). Kumar and coworkers (Ref. 7} have recentl y indi cated t he prognosti c si qni f icance of microscopic vascular invasi on l~i th i n the tumor. Hil ms' tumor in adol -

escents and adults has been described in previous studies and one point relevant "to our case ,is the fre quency of calcificat ion in the tumor in older individuals (Ref. 9,10). The demonstration of ca l cification both roentgen-ographi cal ly and pa thologically i s no greater t han 5% in chil dren but is 30 - 40% in adul t s.

As of late August , 1976 , the patient was doing well and has no evi dence of recurrent di sease.

Refe rences

1. Bond, J .V. Prognosi s and treatment of Wi lms' t umor at Great Ormond Street Hospital for Sick Chi ldren - 1960-1972, Cancer 36: 1202 , 1975.

2. O'Angio , G.J . et al. The treatment of Wilms' tumor . Results of the Nat ional Wilms' Tumor Study. Cancer 38: 633, 1976 .

3. Dehner, L.P. Pediatric Surgical Pathol ogy, St . Louis, The C.V . Mosby Co., 1975, p. 508-510 .

4.· Jenkin, R.D .T. The treatment of ~/i lms' tumor. Pedi atr. Cl ini c. North Am. 23: 147 , 1976.

5. ,Jereb, B. and Sandstedt, 8. Structure and size versus prognosis in nephroblastoma, Cancer 31: 1473, 1973.

6. Kenny , G. M. , et al . Erythropoietin l evels in Hilms' t umor patients. J. Urol. 104: 75B, 1970.

7. Kumar, A.P.' M. et al. Capsular and vascular invasion: jmpor tant prog-nostic factor s in l~ilms' tumor, J. Pediatr . Surg. 10: 301, 1975.

8. La~1ler, ~/ . , et al. Hi lms' tumor - histologic variation and prognosis. Cancer 36: 11 22 , 1975.

9. Merten, O.F . , et al . l~ilms' tumor in adolescence . Cancer 37: 1532, 1976 . 10. Olsen , B. and Bischoff, A. Wilms' tumor in an adult. Cancer 26: 2, 1970. 11 . Shal et , M. F. et al . Erythropoietin-producing Wilms' tumor . J . Pediat r . 70 :

615, 1967. 12. Wi qger, H. J . Histopathol ogy of ~/il ms' t umor and related l es ions in

Wi lms' Tumor , Pochedly, C. and Mill er, 0. (Edr.), Ne1·1 York , Jolil"'l'/ iley & Son, 1976, p. 103.

Case 9 - Li ver - Biliary ciirhos.i s secondary to extrahepati c biliary atres ia

The diagnosi s of bili ary cirrhosis secondary to extrahepati c biliary atresi a is not a subt le one i n' the microscopic section from t hi s case . As most of you know, the di f ferential di agnosis oeb1een "neonatal hepatiti s" and bil iary atresia is not always strai ghtfor1~ard especi ally in a needl e biopsy. Any number of laboratory determina ti ons have been utili zed over t he last few years in an at tempt to establish the diagnosis without an exploration and biopsy. Serum 5'-nucl eotidase, alpha- fetoprotein and most recently t he determination of serum lipoprotein-X levels (LP- X) before and after chol estyramine have been used . Campbell and Wil l iams have reported that a fall i n LP-X after cholestyramine i s evidence of patent extrahepatic bi le ducts; an elevation is i ndicat ive of an atresic system. One of the pri nci pa 1 reasons to avoid exploratory surgery is based, in part , upon the studi es of Thaler and f-e lli s (Ref .l 2) and others tha t only 5% of extrahepatic atresia are potential l y correctable and that the morbidity and mortality of neonatal hepati ti s are increased with surgery . A recent study by Lawson and Boggs (Ref. 10) contradicted the Thaler and Gellis exoer ience regarding the surgical risk of operating upon a child with neonatal

.•

hepati.tis.

There have been a number of clinicopathologic studies relating to t he differentiation of neonatal hepatitis from extrahepatic atresia. Many of these strike a rather pessimistic note about the morphologic distinction but the following features have been the most useful to me: 1) excessive bile duct proliferation in the portal areas, extension of these ducts alonq bands of fibrous tissue into t he lobule and bi le thrombi - all in extrahepatic atresia , 2) panlobul ar gi ant cel l transformation in neonatal hepati t i s versus peri portal giant cel l cha n~e in extrahepatic atresia, 3) aci dophi l ic bodies in neonata l hepatitis and 4) extens i ve extramedull ary hematopoiesi s in neonatal hepat i t is (Ref. 3). Although the presence or absence of these f indings are not full proof, the correct diagnos i s can be establ ished and confirmed at surqery or foll o1~-up in 90% or more of cases.

The major devel opments or "topics in the area of neonat al hepatitis-extrahepatic atresia are the following: 1) the concept of infantile obstructive cholangiopathy (IOC), 2) multiple etiologies of neonatal hepatitis and 3) the hepatic oortoenterostomy or the Kasai operation. Landing (Ref. 9) has formulated the concept of IOC as a common pathogenesis of injuries to the cholangiolar-ductal system of the liver leading to neonatal hepatitis, biliary atresia and the choledochal cyst. Hepatitis 6 has been implicated by Landinq and others (Ref .6) but cytomegalovirus, rubell a and inborn errors of metabolism such as alpha-1-antitrypsin deficiency are other ·wor t hy candidates. The dynamics of the destructive process and the timing may ~te ll expl ain t he success of t he Kasa i operation whi ch is al most excl usi vely confined to t he first 12 weeks of 1 i fe. Bot h Landing' s papers and l~ i tz l eben' s edi t ori a 1 comments are wor th reading (Ref. 8 , 9, 13) . I t i s generally, appreciated that the gi ant cell transformation of t he neonat al hepatoc.Yte i s a unique response at this age but is nonspeci f ic in regard to an etiologic agent . Thi s point has been made in the preceding comments about IOC. The therapeutic frustration 1~hich has been associ ated with extraheoatic biliary atresia is as 11ell known t o the pathologist and surgeon alike. Recently, Kasai (Ref. 4,5) has devised the hepatic portoenterostomy based upon his earlier experimental work and later clinical observations that there l·tere salvagable remnants of extrahepatic bile ducts during the neonatal period. Since these ducts are eva~scent, it is critical that this operation is performed very early in life. The demonstration of microscopic bi le ductules is mandatory to the success of the operation. Kasai has reported favorabl e results with the establi shment of bile drainage in 70-80% nf cases but in the Uni ted States, the success of the procedure has approached Kasai' s or failed mi serabl y as Camrbel l and his co~10rkers have reported. One of t he major compl icat ion·s of the ooerati on i s t he develooment of ascend-ing cholangi t is (Ref . 7) . Inspite of this, t he hepati c por toenteros tomy poten-tially represent s a s i gnificant t heraoeuti c advance in an area staqnated by surgi fa il ure.

References

1. Brough, A.J. and Bernstein, J. Conjugated hyoerbilirubinemia in early infancy, Hum. Pathol. 5: 507, 1974.

2. Campbell, O. P. and Williams, -G.R. Identification of the jaundiced infant who is likely to recover without surgical intervention, Ann. Surg. 184: 89, 1976.

3. Dehner, L.P. Pediatric Surgical Pathology, St. Louis, The C.V. Mosby Q) • • 1975, p. 340- 344.

4'. Kasai, 11. Treatment of biliary atresia with special reference to

5.

6.

7.

8.

9.

l 0.

ll.

12.

13.'

he'patic portoenterostomy and its modifications, Prog. Pediatr. Surg ., 6: 5, 1974 Kasai, 14. et al. Follow-up studies of long-term survivors after hepatic portoel]terostomy for "uncorrectable" biliary atresia, J. Pediatr: Surg. 10: 173. 1975. Kattamis ~ C.A. et al. Australian antigen and neonatal hepatitis syndrome, Pediatrics 54: ·157, 1974 . Ktbayashi, A. et al. Ascending cholangitis after successful surgical repair of biliary atresia, Arch Dis. Ghil~. 48: 697, 1973. Landing, B.H. Changing approach to neonatal heP.atitis and biliary atresia, Pediatrics 53: 647, 1974 . lal)ding, B. H. Consideration of the pathogenesis of neonatal hepatitis, biliary atresia and choledochal cyst - the concept "Of infantile obstructive ctiolangiopathy, Prog. Pediatr. Surg . . 6: 113, 1974. lawson, E. E. and Boggs, J : [).. long-term follow-up of neonatal hepatitis: safety and value of surgical exploration, Pediatrics 53: 650, 1974.

,• .. •; '< :

lilly, J .R. et al. Surgery of biliary atresia. Current status, Arch. Surg. ' 129: 1429, 1975 . Thaler , M. M. and Gellis, s.s. Studies in neonatal hepatitis and bil iary atresia, Am. J . Dis. C.hild. 116: 257, 262, 271, 280, 1968. Hitzleben C. l. Etiology (ies) of infantile obstructive cholangiopathy, J. Pediatr. 88: 909, 1976.

' Case 10- Liver - Reye's syndrome variant (?) with submassive necrosis The protocol indicated the complicated nature of this child's clinical

presentation and subs'equent course which terminated in death approximately 13 days from the earliest symptom. A needle biopsy of the liver ~1as performed on the third hospital day and it showed extensive fatty change (metamorphosis) of the micro- and also macrovesicular type in the hepatocytes . In addition, there was hepatocellular degeneration and necrosis in the midzonal areas with some i nvolvement centrally. The hi stologic appearance ~1a s puzzling in this regard but all of the other clini cal and. l aboratory f indings supported the impression of Reye's syndrome. Various supportive measures 11ere employed but the patient died. At autopsy, there ~1as marked edema of the brain (800 gm); the heart was large (42 gm) and pale yellow; the kidneys were swollen (75 gm) and pale and the liver (210 gm) had a mustard-yellow colon and a fine , reddish mottling on cut surface. The secti.ons of the heart and kidneys ~1ithin (tubul es ) contained prominent amounts of cytoplasmic l ipid. There 11as e.x tensive fatty change throughout those areas of the liver where the parenchyma was preserved . Rather than the fine lipid vacuoles which· are characteristically seen in Reye's syndrome, the droplets were larger and tended to displace the nucleus. An additionally striking feature was the presence of hepatocellular necrosis, primaril y centri- and midzonal as initial ly appreciated in ·the biopsy but more extensive and confluent at autopsy.

What 1~as the nature of this child's disease? From the clinical stand-point, · an infant who becomes progressively irritable and has hepatomegaly shortly after a non-specific viral illness should be considered a likely victim of Reye's syndrome (Ref . 6, 8, 10). The laboratory values, including an el -evated blood ammonia not described in the protocol , were thought to be compatible with the diagnosis. After the 1 iver biopsy 11as examined, there was some be-wilderment because of the hepatocellular necrosis. The question of some environ-mental hepatotoxin, anoxia, and a virus, possibly hermes simplex was posed . · Toxicologic screening and viral cultures were performed and all were negative.

Does this pati ent have Reye ' s syndrome or fulminant viral hepatiti s with submassive necrosis? It can be argued that the hyperbilirubenemia is a feature against the diagnosis of Reye's syndrome as ~1ell as the submassive hepatic necrosis. If this case represents viral hepatitis, the initial liver biopsy was certainly most unusual for that disease. Toxic hepatitis is a distinct poss ibi l ity especially with t he zonal distribution of changes and the fatty change. A reasonabl e effort was ma.de to exclude some toxin t hrough fluid and tissue toxicologic examination at ~utopsy.

This patient reminds me of the thre.e cases which Gall and c01·rorkers (Ref. 7) reported in 1975 as "acute liver disease and encephalopathy mimicking Reye synd.rome" and the reviev1 of 7 cases by Brown and Ishak (Ref. 5). The children in the former study were 23-months, 4-years, and 6-year s old. His tolagical ly, centrilobular necrosis and minimal fatty changes were present in the liver. Circulatory failure, carbon tetrachloride, toxins, drugs and infectious disease were discussed by Gall and co~rorkers as possible related etiologies but un-proven. Ultrastructurally, similar mitochondrial alterations vtere present in the hepatocytes as those described in Reye' s syndrome (Ref. 9). Br01·m and Ishak (Ref. 5) suggest that fatty ac ids; represent t he hepatotoxin .

The gross and microscopic features of Reye 's syndrome in the liver have been documented on a number i:if occasions . (Ref. 1 , 2, 4) . Bove and coworkers (Ref. 2) have recently revie~1ed their experi ence with l iver biopsies from 49 children. They make the point which has previously been made that hepato~ cellular necrosis is either absent or inconspicuous. Isolated necrosis of hepatocytes may occur- in the periportal area. It was interesting to note that 1 of 49 children had centrilobular necrosis in a bi opsy and in 2 children at autopsy who did not have a previous l i ver biopsy. These authors made the following statement, " \~e have considered central necrosis to be a superimposed lesion, and if unaccompani ed by sever-e f atty change in the intact portions of the lobules, we ~1ould be reluctant to make a diagnosis of Reye·' s syndrome."

References '

1. Bove, K.E. The character and speci ficity of the hepatic lesion in Reye's syndrome in Reye' s Syndrome, Pollack, J.D . (Ed.), Ne1~ York, Grune and Stratton, 1975, p. 93-116.

2. Bove, K. E. , et a 1. The hepatic 1 es ion in Reye ' s syndrome. Gastroenter-ology 69:685, 1975.

·3. Bradel, E.J. and Reiner, C.B. The f ine s tructure of hepatocyte.s in Reye's synd·rome. Pollack, J.D. (Ed . ), Ne~' York, ·Gruhe and Stratton, 1975, p. 147-1 58.

4. Brown, R.E. The pathology of Reye ' s syndrome: an over.view in Reye's Syndrome, Pollack, J.D. (Ed . ), New York, Grune a.nd Stratton, 1975, p. 77-92.

5. Br01~n, R.E. and Ishak, K.G . Hepat i c zonal degeneration and necrosis in Reye's ?Yndrome . Arch. Pathol. 100:123, 1976.

6. Chaves-Carba 11 o, E. , et a 1 . Encepha 1 opa thy and fatty i nfi ltrati on of the viscera (Reye-Johnson syndrome), Mayo Cl in. Proc. 50:209, 1975.

7. Gal l , D.G., et al. Acute liver disease and encephalopathy mimicking Reye's syndrome. J. Pediatr. 87:869, 1975.

8. Partin, J.C. Reye '~ syndrome (encephalopathy and fatt y l i ver). Diagnosis and treatment. Gastroenterology 69:5:11 , 1975. .

g. Partin, J.C. , et al . Hitochondrial ultrastructy,re in Reye ' s syndrome (en-cephalopat.hy and fatty degeneration of the viscera)., N. Engl. J. Med. 285: 1339, 1971.

10. Schubert, W.K., et al. Encephalopathy and fatty liver (Reye's syndrome) . Prog . Liver Dis . 4:489, 1973.

Case ll - Colon - Ne.crotizing enterocol i tis (NEC) of infancy

A low-weight for dates or premature infant who has sustained some stress such as anoxia is the usual vic tim of necrotizing · enterocolitis. Al though NEC was seemingly recognized ·as ear ly as 1825 by Siebol d, the past 10 years have witnessed the publ i.cation of numerous reports i n the pediatric and surgi cal literature. r~ost pathologists ' initial "introduction to. this disorder took the form of frozen sections l ooking fo:r ganglion cells in a chi l d suspected of havin9 ·Hirschsprung's di sease or at the autopsy table. George Fetterman, the former pathologist at the Children ' s Hospital of Pittsburgh, editorial ized in 1971 about NEC and whether it was an old probl em with a new name or bone fide ne1'1 entity (Ref . 4) .

Perforation of the b01·1e 1 especially the colon either spontaneously or associated with exchang.e transfusion has been appreciated in the neonate f or some time (Ref. 6) . Two types of l esions have been reported in bowel: 1) an

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isol ated perforation in a ndrmal segment of colon; or 2) multiple perforations ~li th diffl!se necrotizing enterocolitis.

Clinically,. t he age of onset of NEC is approximately 6-8 days old (range 1 - 25 days). Abdominal di stention , apnea, vomiting,diarrhea (sometimes bloody), hypothermia and mild jaundice are some of the more common present i ng features (Ref. 2, 3) . In the experience at the University of ~1innesota, g]% of the children with NEC 1-1ere premature and 4.7% of the neonatal admissions were for NEC (Ref. 5). Roentgenographically , adynamic ileus and pneumatosis cystoides intesti nalis were t he commones t findings . In the various seri es , pneumatosi s intestinalis was present in 75-90% of the children. Pneumoperitoneum and gas in the portal vein were other less f requent but more ominous radiographi c changes (Ref. l). Both medical and surgical regimens have been utilized in the manage-ment of these children. At Babies Hospital, Ne1-1 York, intesti nal obstruction, pneumoperitoneum and peri tonitis.were the indications for surgery (Ref. 8). Disseminated intravascular coagulation and metabolic acidosis were additional indicat ions for surgery at the University of Minnesota (Ref . 5). In the for-mer series. the overall survival was 22% (medical, 16%; surgical, 30%) and the latter ser ies v1as 35% (medica l , 44%; surg ical , 31%). The earli er cl inical re-cognition of NEC has ref lected i tself in a significant improvement in surv ival and more cases are now bei ng managed conservatively (Ref . 9).

The gross and microscopic findings in the semin?r case are typical for NEC . It is apparent f rom the protocol that the baby was desperately ill and a resection could no t be performed . Grossly, the ileum and the colon are the most freq·uent sites of invol vement foll owed by the jejunum. [n the more severe cases , the il eum appears to represen t t he cent ra 1 si te form 1•1hi ch t here is proximal (jejuna-ileal) and distal (col onic) involvement . The affected segment has a dusky, hemorrhagic appearance to the serosal surface and perforations are occasionally recognized in the gross examination. When the pneumatosis is severe, blebs are di scernible on the external surface . The mucosa is hemorrhagic and microscopically, as in this case , there is coagulative necrosi s of the epithelium. In spite of the extensive mucosal and submucosal necrosis, there is a minimal inf lammatory reaction. The cysts are conf ined to the submucosa. There is no react ion in the cysts which contrasts 1~ith pneumatosis cystoi des in adul t s. A giant cel l reaction i s present in the wal l of the cysts in the benign adult form. Transmural necrosis or perforation were not identified in the sections which 1 examined.

Among those children who survive, a long-term compl ication is t he develop-ment of foca l stenosis of the bowel (Ref. 7).

References

1. Bel l , R.S . , et al . Roentgenographic and clinical manifestations of neonatal necrotizing enterocolitis. Experience with 43 cases. Am. J . Roentgenol. Rad ium Ther. Nucl . Med. 112:123, 1971.

2. Dehner, L.P . Pediatric Surgical Pathology , St. Louis, The C. V. Mosby, Co. 1975, p. 278-280.

3. de Sa, O.J . The spectrum of ischemic b01·1el disease in the newborn. Per-spect. Pediatr. Pathol. Vol. 3 (in press, 1976 ).

4. Fetterman, G.H. Neona~l necrotizing enterocolitis - old pitfall or new problem? Pediatr ics 48:345, 1971.

5. Frantz, I.O ., et al. Necrotizing enterocolitis . J. Pediatr. 86:259, 1975.

6. Hardy, J .D. , et al. Intestinal perforation fo l lowing exchange transfusion . . Am. J . Dis. Child. 124:136, 1972.

7. Joshi, V.V., ~tal. Neonatal necrotizing enterocolitis. Hi stologic evi-dence of healing . Am. J. Dis. Child. 126: 11 3, 1973 .

8. Santulli , T.V., et al. Acute necroti zing enterocolitis in infancy : a review of 64 cases. Pediatrics 55:376, 1975.

9. Torma, M.J. et al. Necrotizing enterocolitis in infants . Analysis of forty-five consecutive cases. Am. J . Surg. 126:758, 1973.

Case 12 - Spleen - Histiocytosis, malignant

The section of spleen which I examined disclosed an infiltrative process mainly confined to the red pulp areas . Most of the tumor cell s wer e relative-ly uniform in size, outline and other cytologic characteristics. The nuclei were moderately hyperchromati c, and there wa~ some indentation of the nuclear membrane. Mitoses were present but I did not see any abnormal forms. An acidophilic to amphophi lic rim of cytoplasm was identi fied in most of the ovQid cells with their distinct cellular membranes. Erythrophagocytosis was incon-spicuous in my section.

These cel l s had nearly all the features which f associate with a histio-cyte and there was sufficient atypia to strongly suggest that the disorder was malignant. Certainly, the attenuated cl inical history lasting no more t han 4 days l ends credence to t hat i nterpretation. I would like to say that we have encountered atypical hi stiocytic infiltrates in lymph nodes, spl een, l iver and skin in children with acute, fulminant Epstein-Barr virus and cytomegalovirus infections. It is sometimes difficult at the l ight microscopic level to be certain whether the cells represent immunoblasts or histiocytes. I have not been informed whether viral cultures were obtained.

Assuming that this case represents an example of histiocytosis, how does it relate to the general histiocytic disorder known as histiocytosis (Ref. 3, 4). The monocytes-macrophages are the basic cell ular elements of the neoplastic "hi stiocytoses." Based upon cl inica l and pathologic considerations. Rappaport (Ref. 5) distinguished three groups: a reactive prolif eration of histiocytes with a known metaboli c, immunologic or i nfectious orig in; a malignant prol ifera-tion of histiocytes (malignant histiocytosis) and the elusive histiocytosis X or "differentiated histiocytosis. " Since the reactive histiocyte may be qui te atypical, I would like to reserve the option that a pathogen may be involved in our patient since the symptoms of fever, a productive cough, irritability and the exanthemous rash are so suggestive of an infection . It is also known from the two larger series of malignant histiocytosis that the clinical presentation can rapidly invol ve and termi'nate i n death within a few days, weeks or months (Ref . 2, 7).

According to most authorities , the monocyte is derived from a pl uripotential stem cel l through the sequence of monoblast, promonocyte and the mature cir-cul ating form (Ref. 1, 6). Further differentiation occurs in the monocyte as i t becomes a tissue macrophage or histiocyte through the acquisition of increased phagocytic and lysosomal activities. The Golgi apparatus and lysosomal granules

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. are more prominent in t he macrophage-histiocyte than the monocyte . As antic-ipated, DNA replication i s markedly dimi nished. It has been accepted by most investigators that the Langerhans cel l with its characteri stic cytoplasmi c marker, the Birbeck granule or X body is the neoplastic cell of the differen-tiated histiocytoses . Initially, there were those 1·1ho considered the Langerhans cell in its native state in the epidermis as a type of melanocyte but only the dendri tic na ture of these cell s ~1as t he common denominator. Cytochemical ly, the melanocytes contain tyrosinase but, in contrast, the Langerhans cel ls con-tain hydrolytic enzymes such as acid phosphatase and nonspecific esterases . These cells in tissue culture are also capable of phagocytic activity although it is uncommon to identify phagocytosis in the lesions of histiocytosis X. The ~teight of evidence, although not indisputabl e , is that t he Langerhans cell is mesenchymal in derivation, migrates into the ski n during fetal l ife and is most closely related to the monocyte-macrophage.

The histologic dif ferentia l diagnosis of lesions wi th sinusoidal pro-li feration incl udes sinus histiocytosis 1~it h or without massive lymphadeno-pathy (Rosai-Dorfma n disease ), metastatic carcinoma espec ially mali gnant mela-noma and lymphoepithel ioma, leukemic reticuloendothel iosis (primarily adults), granulocytic sarcoma {chloroma) and histiocytic lymphoma. lmmunoblastic lymph-adenopathy and infectious mononucleosis with partial or compl ete effacement of the fo lli cular architecture and interfollicular hyperplasia are other consider-ations.

References

1. Albrecht, R.M. and Hong, R. Basic and clinical considerations of t he monocyte-macrophage system in man. J. Ped i a tr. 58:751 , 1976.

2. Byrne, G. E., Jr., and Rappaport, H. t~al ignant histiocytosis. Gann Monogr . Cancer Res. 15:145, 1973.

3. Dehner , L.P. Pediatric Surg ical Pathology, St. Louis, The C. V. Nosby, Co., 1975, p. 649-655.

4. Ne~1ton, H.A. , Jr., and Hamoudi , A.B. Histiocytosi s: a histologic class-ification 11ith cl inical correlation. Perspect. Pediatr. Pathol. l :251, 1973.

5. Rappaport, H. Tumors of the Hematopoietic System, Atlas of Tumor Pathology. Armed Forces Institute of Pathology, Jg66 , p. 48-90.

6. Unanue, E.R. Secretory function of mononuclear phagocytes. Am. J . Pathol. 83 :396, 1976.

7. Warnke, R.A., et al. t~lignant histiocytosis. I. Clinicopathologic study of 2g cases. Carycer 35:215, 1975.

Case 13 - Lymph node , axil lary, r ight - Malignant lymphoma, poorly differentiated lymphocytic (lymphoblastic) type

The only diagnotic point that the majority of pathologists will agree upon in this case is that this 19-year-old ma l e has malignant lymphoma, that i t is diffuse and that there are no Reed-Sternberg cells . There are some ~1ho probably have fit this case into their own classification or one that t hey are currently espousing. To say that the situation in terms of nomenclature of non-Hodgkin ' s mal ignant lymphomas is chaotic may well be one of the current understatements (Ref. 5, 6) . In our institution, there is still an attempt to adhere to t he

Rappaport-Gal l classificqti on of non-Hodgkin ' s ma l ignant l ymphomas, t hat is ma l ignant lymphoma, hist i ocyti c type; poorl y differentiated lymphocytiC> well-differentia.ted lymphocytic and undifferentiated (Burkitt's lymphoma) (Ref. 9·).

In t his case, it is apparent that the ent ire node has been replaced by a diffuse prolifera~ion or poorly differentiated lymphoid cells. There is some convo 1 uti on .of the nuclear membranes. Chromatin c 1 ampi ng ra t her than di sper·sion is presetjt. Mitoses are abundant and a focal "starry-sky" appearance is apparent.

The differential diagnos i s of this malignaht lymphoma resides between malignant l ymphoma, poorly di fferentiated (l ymphobl astic) type and undi f fer entiated (Burk.i t t ' s) type . From the c 1 inica 1 standpoint, genera 1 i zed per i pheral 1 ymph-adenopathy is an extremely unusual presentation for Burki tt's· lymphoma. A gastrointestinal neoplasm or abdomi nal -retroperitonea l lymphadenopathy are the present i ng features of American Burkitt ' s lymphoma (Ref. 1, 2, 8) . We are n.ot to l d, but if a mediast inal mass, bone marro~1 or periphera l blood involvement were . present then )ymphoblastic lymplioma would be the di agnosis on clinical grounds :' ~ (Ref . 7) . Histological l y, the tumor cells were certainly immature hut ~1ithout the~ ··· "stem-cel l " appearance of the Burkitt's cells. Functional studies would have been helpful in that the Burkitt's cel ls have monoclonal immunoglobulins on the sur-face indicative of a B- cell (Ref. 4) . In. this case, the marker studies may well have c haracterized t.he tumor as T-cell or even ni l -cell . A very convolut ed nucleu··s would have been more suggest ive of a T-cell neoplasm.

Prognost ically, both American Burkitt's lymphoma and poorly-diff erent iated (lymphoblast i c) lymphoma have a very poor outlook (Ref. 10, 11). Death usual ly occurs in less than a year after diagnosis.

References

1 . Arseneau, J.C .. , et al . American Burkitt's l ymphoma: a c l inicopathol ogi c study of 30 cases. I. Clinical factors relating to prolonged survival. Am. J . Med. 58:314 , 1975.

2. Banks, P.M . , et· a l . American Burkitt's lymphoma: a cl i nicopathologic study of 3D cases . I I. Pa tho 1 og i c corre 1 ati ons. Am . J . 1•1ed. 5~: 322, 1975 .

3. Barcos, M.P. and Lukes, R. J . Mal ignant l ymphoma of convoluted lymphocytes: a new ent ity of possible T-cell origi n in Conflicts in Chi l dhood Cancer . An Eval uation of Current Management. Sinks, L.F. and Goddenor, J . D. (Eds.) Progr. Clin. Bi ol. Res. 4: 147, 1975.

4. Benders , R.A. ,. e t al. "B" cell origin of ma l ignant cells in a case of American Burkitt ' s lymphoma. Cancer 36:161, 1975 .

5. Dehner, L. P. Pedi atr ic Surgical Pathology, St. Louis, The C. V. ~rosby, Co . , 1975, p. 655-663.

6. Dorfman, R.F. The non-Hodgkin's lymphomas, in The Reticuloendothelia l Syst em. Rebuck, J . W., et al. (Eds .), Bal timore, The Hil liam and Wilkins, Co . 1975, p. 262- 281.

7. Natliwani, B.r4., et al. 1-lalignant l ymphoma, lymphoblastic . Cancer 38 : 964 , 1976 .

8 . Nkrumah, F, K. and Perkins, I. V. Burki tt's lymphoma . A cl i nica l study of 110 cases. Cancer 37:671, 1976.

9. Rappaport, H. and Braylan, R.C. Changing concepts in the c l assification of ma l ignant neopl asms of the hema t opoietic system, in The Reticuloendothel ial System. Rebuck, J.H., et al. (Eds.), Bal timore, The Wil l iam and Hi lki ns, Co . , l 97 5, p. 1-1 9 ..

10. Wollner, N., et al . Non-~odgkin's lymphoma in children: a review of 104 cases, in Confl i cts in Childhood Cancer. An Evaluation of Current l·tanage-ment. Sinks, L.F. and Goddenor, J.O. (Eds.), Progr . Cl in. Biol. Res. 4 : 179, 1975 .

11. l~ollner, N. , et al. Non-Hodgkin's lymphollla in chi l dren . A comparative study of two modalities of therapy. Cancer 37:1 23, 1g?6.

Case 14 - Soft tissue, l o~1er extremity - Synovial sarcoma

Hhen t his 13-year-ol d boy presented and after an X-ray 1vas taken, t here was l ittle questi on that he did not have a malignancy of some type. A large soft tissue density was present and there was destruction of the proximal tibial metaphysis. The three diagnostic considerations were an osteosarcoma, Ewing's tumor or a pr imary soft tissue malignancy. Of these choices, osteosarcoma ~/as t hought to be the leas t l ikely because of t he lack of bone produc t ion by the tumor and the re l ative l ack of a periosteal react ion. ' It was e l ected t he refore, to perform an inci s ional bi opsy with frozen section consultation to insure that diagnostic t issue had been removed . The orthopedic surgeon was not terribly concerned about a specific histopathologic diagnosis. For many of you, th i s approach is certainl y a reversa l of a standard procedure of a few years ago 1·1hen an immedi a te amputati on hung in the ba l ance of a frozen section i nter-pr etation . It has been shown that a delay of 24-48 hours does not compromise the prognosis and the extra assurance of permanent section is wel l 11orth the de l ay . In fact , I have not participated in a frozen section consultation in the past 5 years at Barnes Hospital or University Hospitals in ~1hich the amputa-tion for an osseous or soft tissue malignancy was performed a t t nat operation. In our case, we to l d the surgeon that the fro zen section showed a spind le cell neopl asm. Our differential diagnos i s included synovial sarcoma and fibro-sarcoma with less consideration to a ma l ignant fibrous hi stiocytoma and the spindled component of an osteosarcoma. The permanent sections revealed a spindle cell tumor with small epithelioid nests v1hich v1e thought sufficiently biphasic to warrant a diagnosis of synovial sarcoma. ·

In the pas t , t he diagnosis of synovia l sarcoma ~1as a dreaded one . An early review of synovi al sarcomas in chi ldhood by Crcicker and Stout {Ref . 7) s howed that 62.5% of patients 11ere either dead or 1 iving 1·1i t h tumor . folost tumor s in that series (84~) were Jocated in the lower (20 cases) or upper extremities (16 cases). The region of the knee, the th i gh and hand 1•1ere the specifi c si tes of predi l ection.

Amputation has been the treatment of choice but r ecentl y, there has been a trend to perfor m a wide exci sion, if possi ble, foll o~1ed by l ocal i rradiation and chemotherapy. This was the plan for our patient and an en bloc excision includi ng the proximal tibia 1•1as performed . Unfortunately, the patient has required 5-6 admissions for a staphyl ococcal wound infecti on . He 1·1as back in the hospital abou t 2 weeks ago f or a r epeat debridement. Irrad i at i on and c hemo-therapy had not been institut ed as of 6 months post-operat i ve l y . There has been no evidence of l ocal recurrence or metastasi s.

Synovial sarcoma was third i n frequency among the 135 soft tissue sarcomas in children reviewed at the Mayo Clinic (Ref. 7). Rhabdomyosarcoma and "sarcomas of undetermi ned hi s t ogenesis" were more corm1on . The Memori a l Hospital group

have examined their series ai 24 cases ·of synovial sarcoma in children with an a.ge range of 20 months to 15 years but over 50% of patients were between 13 and 15 years (REf. 5). A feature of synovial sarcoma is the prolonged duration of symptoms which can l ast f or 3-5 years before a definitive diagnosis . We have seen a case of a 15-year-old boy wi th sympt oms for at l east 3 years. His pediatrician-father thought that he 1~as a hypochondriac . Anot her feature of synovial sarcoma is the frequent cal c ification in the tumor as demonst rated roentgenographica·ny. Approximately 15% of cases have, at some time, nodal metastases (Ref. 4).

Pathologically, the tumor in the seminar was juxtacort ical and invaded bone. The b'iphasi,c pattern was wel l-represented in nearl y all sect ions. One hi stol ogic feature ~1hich I have found hE!l pfu l is the. multilobular pattern of growth. The lobules expand and compress the adj acent soft tissues. Encapsula-tion is rarely present and the lack of ci'rcumscri pti on can lie a problem. Ehzi nger has point ed out the frequency of mast cel l s in synqvial · sarcoma. The diff e.rential diagnosis especial ly when the biphasic pattern is not obvious i ncl udes f i bro-sarcoma, fibrous histiocytoma, ma l ignant Sch1·1annoma and leiomyosarcoma . A cl ear cel l sarcoma of tendon sheath origin should also be mentioned. Cadman and coworkers (Ref. l) and MacKenzie (Ref. 6) have t(le 1 argest general rev i ews of synovial sarcoma. Fernandez and Hernandez (Ref. 3) have discussed t he role of el ectron micr oscopy in the diagnosis.

References

1. Cadman, N. L. , e.t a 1. Synovia 1 sarcoma.. An analysis of 134 tumors. .Cancer 18:613, 1965.

2. Crocker , D. W. and Stout, A.P . Synovial sarcoma in children. Canc'er ·12: 1123, 1959.

3. Fernandez, B.B. and Hernandez, F.J . Poorl y differemti ate'd synovial sarcoma . A l ight and elect ron mi croscopic st udy. Arch. Pathol. 100:221, 1976.

4. Fine, G. , et al. Soft tissue sarcomas: the i r clinical behavior and course and influencing factors. Proc. Seventh Cancer .Conf. 7:873, 1973.

5 .. Lee, S.N., et al. Synovial sarcoma in ehildren. Surg. Gynecol. Obstet. 138:701, 1974. .

6. MacKenzie, D.H . Synovial sarcoma: a review of 58 cases . Cancer 19:169, 1966.

7. Soule, E.H., et al. Soft~tissue sarcomas of inf ants and chi l dren : a clinicopathol ogic study of 135 cases . Proc. Hayo Cl i n. 43:313, 1968.

~ ·Case 15 - Soft tissue, l01~er extremity- Al veolar r habdomyosarcoma

The patient ' s hi.story dated back to 6 years of age when her left l eg ~1a s amputated for a soft tissue mal ignancy which was diagnosed at that time as a "liposarco.ma." She di d wel l withol!t adj unctive therapy or f urther symptoms until she was 13-years-old. At that time, the symptoms and signs pointed to a cardiac probl em ·c.haracterized by sudden loss of cardiac .output. A polypoi d neoplasm was partial ly excised from the left ventricular septum. Gross l y, that tumor measured 3. 5 x 1 .·5 'em; and had a smooth, endothel ia l ized external surface . There was· extensive f i brosis at. the t ip of the mass ho~1ever, at the base, there ~1ere nests of hyperchromatic tumor cel l s. Some- of the cells were multi-nucl eated and had acidophil ic cytopl asm. It was apparent that the exci si-on 1~as

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incomplete since tumor was present at the margin of resection. A comparison was made bet1~een the cardi ac neoplasm and the one excised 7 years previously. They were both unquestior.~abl y alveolar rhabdomyosarcomas . She did 1~e ll for almost 11 months and then developed a soft tissue mass of the right leg . Your secti on shows a tumor arranged in large, expansile and i nf i l trating nests of cells . ~lith i n these l arger aggregates, the alveolar p.attern is very distinct. Jil spi te of the size of the ma ss, there 1~as l ittle evidence of necrosis. This lesion 1~as excised because at the t ime, there was no other ev idence of tumor. Approximately 4 mon.ths later, she died ~1ith wi despread tumor .

. This case was chosen to d i scuss the rhabdomyosarcoma, the mos t common soft tissue rna l i gnancy in childhood but also to share the unusual natura l hi story of this particular alveol ar rhabdomyosarcoma (Ref. 1, 2, 5).

Riopel l e and Theriaul t in 1956 v1ere the first to describe the a lveolar rhabdomyosarcoma as a d i stincti ve neoplasm and 2 years l ater , Enter l ine and Horn (Ref. 3) reported thei r 9 cases and compared them ~li th 6 cases of Riopelle and Ther i ault. One of the most im~ortant points stressed by t he·se earl i er authors and applicable today i s the confusion with other neoplasms. The a l veol

The l argest series of alveolar rhabdomyosarcomas in the li terature is the one from t he Armed Forces Insti t ute of Pathology (Ref. 4). Unl i ke the more common embryona l rhabdomyosarcoma which occurs in the head and neck region and pelvis in children, the alveol ar rhabdomyosarcoma oc~ in the extremities (forearm, hand) and trunk. When this tumor is found in the pel vi c reg i on, it i s general l y not associated with an anaton1ic structure such as the bladder, prostate or vagi na bu t rather in the perianal , perirectal , and perineal soft t i ssues. The median age in the AFIP series 1~as 15 years. We have seen a peri-orbita l alveolar rliabdomyosal:'coma in a 2-year-'ol d female, our youngest case . That is another difference - .embryona l rhabdomyosarcoma originates in the orbit but t he alveol ar rhabdomyosarcoma i n the soft tissues around the eye. The natural history of t he tumor was not typified by the seminar case since the med i an survival ~1as 8 3/4 months in the AFIP exP,er ience. Our patient survived over 8 years.

An obvious ques t ion which can be posed is whether thi·s patient developed a second primary tumor (Ref. 6). t•lorpholog ically, the only th i ng that we could say is that they were similar, i f not identical neopl asms. From the therapeutic standpoint, she vtas treated as a second pr i mary tumor. Nha.t about a cardiac me t astas.is from the ori ginal a l veolar rhabdomyosarcoma? Among the 57 cases 1~ith autopsies i n the AFIP series, the heart 1~as the site of metastasis i n 44%. Pratt and coworkers (Re·f. 7) have indicated the apparent predilection for cardiac metas tases in childhood rhabdomyosarcoma. In a sense, we are l eft on the horns of a dilemma.

References

1. Bal e, P. M. and Reye , R. O.K. Rhabdomyosarcoma in childhood . Pathology 7:1 01 , 1 g7s.

2. Oehner, l.P. Pedia tric Surgical Pathol ogy, St . Louis, The C.V . 14osby, Co., 1975, p. ·688-690 .

3. Enterline, H.T. and Horn, R.C., Jr . Alveolar rhabdomyosarcoma . A distinctive tumor type. Am. J . Cl in. Pathol. 29 :356, 1958.

4. Enzinger, F.M. and Shiraki, M. Alveolar rhabdomyosarcoma. An analysis of 110 cases. Cancer 24 :18, 1969.

5. Mahour, G. H. , et al. Rhabdomyosarcoma in infants and children: a clinico-pathologic stydy of 75 cases. J. Pediatr. Surg . 2:402, 1967.

6. Orsmond, G., et al. Alveolar rhabdomyosarcoma involving the heart . An echocardiographi c, angiographi c and patho 1 ogic study. Circul ation, in pr·ess.

7. Pratt, C.B., et al. Metastatic involvement of the heart in childhood rhabdo-myosarcoma . Cancer 31: 1492, 1973.

Case 16 - Soft tissue, chest wall - Skeletal hemangioma

The development of this soft tissue mass was at least historically related to t rauma occurring 4 years previously . Angiographically, i t v1as strongly felt that the mass was malignant . A wide local excision of an ill-defined tumor was carried out. Histological ly, the tumor was i nitially int erpreted as an angio-sarcoma. If this neoplasm had occurred in the breast rather than the soft tissues then that diagnosi s becomes more tenable. The patient is 6-months post-operative and is doing well without further therapy.

In this case, we have a neoplasm which i s composed of a mixture of large, thi ck-walled vascular channels vtith cavernous dil atati on and aggregates of small er vascular spaces . It is this latter microscopic pattern which was fe l t to represent the clearly malignant component . A careful examination reveals that these foci are certainly cellular but there are few, if any, budding and branching structures and the . individual endothelial cells lack significant cyto-logic atypi a. Mitotic figures are generally absent . · The intimate' relationship between the vascu lar prol iferation and the skel etal muscle is appreciated in many of the sections. Dense fibrous connective tissue forming bands are also present . Scattered areas of adipose t i ssue are noted.

Vascular and fibrous tissue tumors represent the largest groups of benign neoplasms of the soft tissues in childhood (Ref. 2). Because of their cellular-ity, the vascular tumors, especially in children, are overdiagnosed, at t imes , as mali gnant. The trap is set particular ly for the cellular (juveni le) heman-gioma of the parotid gland in a small chi ld .

Skeletal hemangiomas are genera l ly diagnosed during the f irst 3 decades of life. Al l~n and Enzinger (Ref . 1) have reviewed the clinical and pathologic features of 89 cases and have divided them into 3 basic morphologic types 1) small-vessel; 2) large-vessel, and 3) mixed. Our case would correspond histological ly with the "mixed" type. The adipose component of the skeletal hemangioma.may be quite striking and thus the tumor has also been des ignated as an "infiltrating angiolipoma." Loca l recurrences of these t umors have been documented in 18% of the AFIP cases but none have metastasized.

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It should be remembered tha t angiosarcoma of the skin and soft tissues i s one of the rares t tumors i n the pediatric age group (·Ref. 3).

References

1. Allen, P.W. and Enzinger, F. l-1. Hemangioma of skeletal muscle. An analysis of 89· cases. Cancer 29:8, 1972.

2. Dehner, L. P. Pediatric Surgical Pathol ogy, St. louis, The C. V. Mosby, Co., 1975, p. 690- 697.

3 . Rosai, J., et al. Ang i osarcoma of the skin. A cli nicopatholog ic and fi ne structural study. Human Pa tho.l . 7:83, 1976.

louis p. dehner . m.d. - uscap · profe:ssor of lj\borator'i hi~ojctne & pa.tj-iolo

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