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Penrose Cancer

General Information

History of the Penrose Cancer Conference

Guest Discussants, Consultants & Acknowledgments

Participants

Penrose Cancer Conference 1998 September 18 and 19, 1998

Schedule

All functions will be held in BROADMOOR WEST unless noted otherwise.

Friday, September 18 7.00 to 8.00 am Registration Rocky Mountain Ballroom

7.00 to 8.00 am Breakfast buffet with Prefunction Area Exhibitors

8.00 to 1 o.oo am Case presentations Rocky Mountain Ballroom Guest discussants

1 o.oo to 10.30 am Break with Exhibitors Rocky Mountain Ballroom Prefunction Area

10.30 to 12.30 pm Case presentations Rocky Mountain Ballroom Guest discussants

12.30 Adjourn

Saturday, September 19 7.00 to 8.00 am Registration Rocky Mountain Ballroom

7.00 to B.OO am Breakfast buffet with Prefunction Area Exhibitors

8.00 to 10.00 am Case presentations Rocky Mountain Ballroom Guest discussants

10.00 to 10.30 am Break with Exhibitors Rocky Mountain Ballroom Prefunction Area

10.30 to 12.30 pm Case presentations Rocky Mountain Ballroom Guest discussants

12.30pm Adjourn

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MUSEUM

Penrose Cancer Conference September 12-13, 1997

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History of the Penrose Cancer Conference

In the eany 1940's, pathologist Lauren Ackerman and oncologisVradiotherapist Juan del Regato, both from Ellis Fischel Cancer Hospital in Columbia, Missouri, published their classic book, CANCER. Diagnosis and Treatment. Their book became the foundation for informal conferences attended by such medical notables as Arthur Purdy Stout, the acknowledged founder of surgical pathology as a specialty. Dr. del Regato often discussed clinical, radiologic and radio-therapeutic data with visiting professionals, laying the groundwork for future cancer conferences.

In January of 1949, at the request of Julie Penrose, Dr. del Regato became the Director and Radiotherapist at Penrose Cancer Hospital, a part of The Glockner-Penrose Hospital. Dr. del Regato decided to develop a more formal conference, primarily for pathologists from the Rocky Mountain area. Although not a pathologist himself, he felt that the Conference would have a more universal appeal with this focus. Under the cosponsorship of the Colorado Society of Clinical Pathology, the Penrose Cancer Seminar debuted on September 10, 1949 in the Little Theater of the Broadmoor Hotel.

Prior to the first formal conference, the only one which focused on a variety of cases rather than on one organ or one major disease, Dr. del Regato sent slide sets of 16 cases to 120 pathologists for their opinions. Conference faculty, Arthur Purdy Stout, M.D., and Lauren Ackerman, M.D., jointly discussed breast, skin, salivary gland, etc. cases. Drs. Stout and Ackerman disagreed on the diagnosis of only three out of the 16 cases submitted. Diagnoses from the other pathologists were more varied. One of the purposes of the Conference, which drew over 500 participants, from both coasts, was to show how frequently good pathologists justly differ in the diagnoses of difficult cases on the basis of morphology alone. Proceedings of the Conference were published in Cancer Seminars, Vol. I, No. I, September 1950.

The second seminar, held on September 9, 1950, concentrated on bone tumors. Dr. Phillip Hodes, Professor of Radiology at the University of Pennsylvania was added to the faculty and continued the following year in that capacity. Dr. Ackerman served as pathologist for this seminar as well as for the third and fourlih events. From that point on, pathologists and radiologists equally shared in conference presentations.

At the sixth conference in 1954, a clinician was added. Usually a surgeon, this new faculty component added yet another dimension to the conference. Since 1954, pathologists, radiologists and clinicians serving as guest speakers have been national leaders in their specialties.

The conferences continued annually at the Broadmoor Hotel. As attendance grew, their location moved from the Little Theater to the Ballroom and finally to the International Center. Dr. del Regato led 24 seminars until his departure from Penrose Hospital in 1972. The Pathology Department continued to coordinate the Conference for an additional five years, until they ended the conferences in 1977.

The Penrose Cancer Seminars were unique. They united the country's premiere pathologists and radiologists in a forum to discuss perplexing problems in diagnosis.

Opinions of the guest speakers, other world experts, and numerous attendees were published annually. The contributions and failures of both tissue morphology and Imaging techniques, as well as the utilization of all modalities to arrive at a correct diagnosis, were Important lessons for all.

The Penrose Cancer Center, a member of Penrose-St. Francis Health Services, revived the Penrose Cancer Seminars after a 16 year hiatus, and in September, 1993, the Penrose Cancer Conference debuted. In the tradition of the earlier conferences, the 1993 conference was again held In the Little Theater of the Broad moor Hotel. Conference participants - comprised of pathologists, radiologists and clinicians -focused their diagnostic skills on the difficult diagnoses of breast and ovarian neoplasms. A total of 91 participants attended.

Today, the Penrose Cancer Center is pleased and proud to continue the tradition of excellence in clinical education as an expression of its mission to manage the most complex malignancies and to assist In the eradication of this disease.

Previous Penrose Cancer Conference Topics

1949 Miseellaneous Tumors AP Stout, LV Ackerman

1950 Bone Tumors PJ Hodes, LV Ackerman

1951 Thoracic Tumors AP Stout, PJ Hodes, LH Garland

1952 Gastric Tumors LV Ackerman, LG Rigler

1953 Tumors of the Small Intestine PC Swenson, WA Meissner

1954 Tumors of the Large Bowel R Golden, RC Hom, Jr.

1955 Tumors of the Urinary Tract FJ Hodges, FK Mostofi

1956 Intracranial Tumors EP Pendergrass, JW Kemohan

1957 Cancer in Children EBD Neuhauser, BH Landing

1958 Bone Tumors PJ Hodes, LV Ackerman

1959 Tumors of Soft Tissues PJ Hodes, AP Stout

1960 Thoracic Tumors B Felson, R Lattes

1961 Gastric Tumors R Schatzki, WA Meissner

1962 Intracranial Tumors JM Taveras, HM Zimmerman

1963 Tumors of the Small and Large S Welin, B Castleman Intestines

1964 Tumors of the Urinary Tract JA Evans, LM Franks

1965 Malignant Tumors in Children JA Kirkpatrick, JM Kissane

1966 Malignant Tumors of the HZ Mellins, H Rappaport Lymphoid Structures

1967 Bone Tumors J Edeiken, HJ Spjut

1968 Thoracic Tumors M Viamonte, Jr., AA Liebow

1969 Gastrointestinal Tumors RD Moseley, Jr., MH MCGavran

1970 Tumors of the Central Nervous HO Peterson, LJ Rubinstein System

1971 Tumors of the Urinary Tract AF Lalli, WC Bauer

1972 Pediatric Tumors J.C. Dumbar, H.S. Rosenberg

1974 Neoplastic and Non Neoplastic N Goodman, M Kuschner Diseases of the Chest

1975 Diseases of the Hepato-biliary A Moss, T Kent and Pancreatic Ducts, Ampulla of Vater and Duodenum

1976 Breast Lesions LM Kallsher, RW McDivitt

1977 Diseases of the S Wallace, R Hartsock, DAG Galton Reticuloendothelial System

1993 Breast Cancer and Ovarian B Eklund, B Gosink, PP Rosen, R Scully Cancer

1994 Soft Tissue Sarcomas RL Kempson, SW Weiss, MS Jochelson, CA Forscher

1995 Prostate and Testicular Cancer Jl Epstein, RD McLeary, JA Smith, Jr., TM Ulbright, AT Stavros

1996 Head and Neck Tumors S Mills, A Mancuso, R Weber

1997 Tumors of the Chest TV Colby, SS Sagel, LP Faber

1998 Tumors of the Gl and Hepato- Rodger C. Haggitt, Eric Biliary Systems VanSonnenberg, BretT. Peterson

Penrose Cancer Conference 1998

Case #1

Case comnbuted by: James G. Smith, MD; James Levanway, MD; Ray Wahl, MD; Robert Sayre, MD; William Chambers, MD; and Bany Lawshe. MD Penrose-St. Francis Health Services, Colorado Springs, Colorado

Cl inical Pr-esentation:

A 78 year old male with a past medical history significant for hypertension, coronary artery disease, diabetes and famil ial adenomatous polyposis, s/p subtotal colectomy with ileorectostomy presented to his primary care physician with anorexia, weight loss and progressive jaundice over one month's time. He denied any other significant sypmtoms.

On physical exam he appeared chronically ill and was markedly jaundiced. No other abnormalities were appreciated.

Laboratory studies revealed a total bilirubin of 14.7 mg/dl, direct 13.5 mg/dl, alkaline phosphatase 1311 lUll, SGOT 64 lUll, SGPT 105 lUll, glucose 164 mg/dl, BUN 37 mg/dl and Cr 1.6 mg/dl.

The patient subsequently underwent abdominal ultrasonography, CT scan of the abdomen and endoscopic retrograde cholangiopancreatography. A diagnostic procedure was then performed.

Nine years later a liver biopsy was performed.

Gross Pathology:

Pancreatectomy with en-bloc In continuity distal stomach, duodenum and spleen (Whipple Resection). In the region of the ampulla of Vater and head of the pancreas was a soft hemorrhagic 2.5 x 2.1 x 0.9 em mass. A separate soft yellow-tan nodule 1.2 x 0.8 x 0.8 em was present in the tail of the pancreas. Nine years later a liver biopsy was performed

Submitted Material:

1. H & E stained slide lilt of Duodenal Ampullary Biopsies ( J_ A ) 2. Photomicrographs of the tail of the Pancreas 3. H & E stained slide tt't.t or Photomicrographs of the liver biopsy { j_ f>)


Case contributed by: James G. Sm~h. MD; James Lavanwoy, MD, Ray Wahl, MD; Robert Sayre, MD; William Chambm, MO; end Barry Lawshe, MD

Penrose-St. Francis Heallh Sef\'ie ... Colorado Springs, Colorado

Case #1

Figure 1: Abdominal CT


Case#2

Ca.se contributed by: Erik VanOs, MD; John Ball, MD; Brock Bordelon, MD; and Eileen Nobles, MD Penrose-St. Francis Health Services, Colorado Springs, Colorado

Clinical Presentation:

A 52 year old female with a remote history of peptic ulcer disease presented with persistent epigastric pain and was referred for esoptiagogastroduodenoscopy. She was noted to have a 3 em diameter gastric ulcer along the Jesser curve, 6 em distal to the GE junction. Enqoscopically the ulcer appeared benign and the remainder of the exam was negative. Biopsies of the ulcer were suspicious for lymphoma, but not diagnostic. No Helicobacter pylori organisms were seen. She was treated with H-2 blockers and returned in two months for a repeat endoscopy. The ulcer had healed, qut the proximal gastric mucosa was clearly abnormal, described as granular and friable. More biopsies were performed and a CT scan of the abdomen was ordered. A surgical procedure was performed.

Gros.s Pathology:

Endoscopic biopsies of the proximal lesser curvature and greater curvature of the stomach were submitted in Hollandes fixative on 2 separate occasions two months (!part. The patient subsequently underwent abdominal exploration.

Submitted Material:

1. H & E stained slideJijj of endoscopic gastric biopsy


Case #2

CaS41 contributed by: Erik VanOs. MD; John Boll MO, Ikock Bo<delon, MD; and Eieen Nobles, MD Penrose-51 Frane~$ Hea~h SeM<:es. ~do Spmgs, Colorado



Case #3

Case contributed by: Todd Wullschleger, MD; Richenda Herren, MD; Gregoty Mears, DO; William Woseck. MD


Mercy Hospital, Fort Scott, Kansas and

Midwest Pathology Consultants, Fort Scott, Kansas

The patient is a 78 year old white female who presented in October of 1996 with a two week history of watery diarrhea. She denied nausea, vomiting, or constipation. She had some intermittent fevers and fatigue, and she had also lost three pounds. A KUB was interpreted as nondiagnosed with gastroenteritis with a possible element of irritable bowel syndrome. She was treated with Lomolil for the diarrhea.

The patient presented again about six weeks later with lower abdominal pain and abdominal fullness. Physical examination revealed a palpable mass in the upper abdomen. A CT scan of the abdomen showed a mass along the greater curvature of the stomach and another mass in the tail of the pancreas. Surgical exploration of the abdomen was performed, with excision of the masses.

The postoperative course was complicated by a left upper quadrant abscess and infarcted spleen, required splenectomy and drainage of the abscess. The patient is alive and well eighteen months after surgery.

Gross Pathology:

A pedunculated spherical yellow white mass 6 x 5 x 5 em was sharply excised from the stomach. Cut surface showed a trabeculated yellow glistening appearance with some myxoid areas. A second specimen consisted of the tail of the pancreas containing a circuumscribed Scm area with a central white fibrous scar and surrounding multiple 1 to 5 mm cystic spaces.

Submitted Material:

1. H & E stained slide 14 of the gastric mass ( 3 4 ) 2. H & E stained slide # 5 of the tail of the pancreas ( ~ :B )


Case#3

Case contributed by: Todd Wullschleger, MD: Richenda Herren, MD; Gregory Maars, DO: William Woseck, MD Mercy Hospi1al, Fort Scott, Kansas

and Midwest Patl'\ok>gy Consultants, Fort Scott, Kansas




Case contributed by. C. Padmalatha, MD; David Clutts, MD; and Tom Colby, MD Memorial Hospital, Carbondale, Illinois

and Mayo Clinic, Scottsdale, Arizona


Case #4

This 57 year old woman with a history of hypertension had been in good health until recently when she developed cramping and constipation alternating with diarrhea. Physical exam at this time revealed a right mid abdominal nontender mass which on the CT scan measured 7 x 4.5 x 7 em. it was located at the area of the umbilicus in the abdomen, more towards the right side. She subsequently had a laparotomy with excision of the mesenteric mass, right transverse colon, partial duodenectomy and partial small bowel resection. The specimen was sent to pathology. postoperatively, the patient did well.

Gross Pathology:

Received in the frozen section room was a resection specimen consisting of an 8 x 4 x 3 em mesenteric mass with an adherent 1 0 em segment of duodenum and 17 em segment of colon. The cut surface of the mesenteric mass was firm in consistency and focally hemorrhagic. The luminal mucosal surface of both the duodenum and the colon appeared normal.

Submitted Material:

1. H & E stained slide tJJ of the mesenteric mass


Case #4

Cue contnbutod by. C. Padmalalha, MD; Dovld CM IS, MD; and Tam Coib'f, MD Memorial Hospltil, Cari>Ondale. ninois

and Mayo Clinic, S<:onS<Iale, Arizona



Case.#5

Case Contributed by Richard Wenham, MD; Erik VanOs, MD; Bret Peterson, MD; Michael Sarr, MD: Gary Keeney, MD

Penrose-Sl Francis Health Service, Colorado Springs, Colorado and

Mayo Clinic, Rochester, Minnesota

Clinical Presentaion:

A 71 year old female with a history of bilateral breast cancer, status post bilateral mastectomies and a family history of carcinoma of the pancreas initially underwent ERCP in 11/94 to evaluate persistent epigastric pain and weight loss. The pancreatic ducts were noted to be markedly ectatic and dilated with numerous possible pseudocysts. The distal CBD was narrowed. A CT scan of the abdomen was performed which confirmed these finding and raised concerns about mass effect in the head of the pancreas. Because of persitent pain she underwent another ERCP in 7/96 with similar findings. Ca 19-9 returned at 237. Cytology from the pancreatic duct was ultimately obtained. The patient was subsequently referred for surgical intervention.

Gross Pathology:

In continuity resection of pancreas, spleen and duodenum. Sectioning of the pancreas demonstrated a dilated pancreatic duct with multiple cystic speces.

Submitted Material:

1. H & E stained slide iiJ of pancreas


Case #5 Case contributed by Richard Wenham, MD; Erik VanOs, MD; Bret Peterspn, MD; Michael Sarr, MD; Gary Keeney, MD

Penrose·St Francis Health Services, Colofado Springs, Colorado and ·

Mayo Clinic, Roch~ster. MinnesOta

Figure 1 ,6: Abdominal CT


Case#5 Case contributed by Richard Wenham, MD: Enk VanOs. MD; Bret Peterson, MD: Michael Sarr. MD: Gary Keeney, MD

P.enrose·St. Francis Health Servfces, Colorado Springs. Colorado and ·

Mayo Glinic, Roch-ester, Minnesota

Figure 1-6: Abdominal CT one year later


Case #6

Case contributed by; William Murchison, MD; Brodie Gerrard-Gough, MD; Barry Lawshe, MD Penrose-St. Francis Health Services. Colorado Springs, Colorado

Clinical Presentations:

A 49 year old male with a history of coronary artery disease who was admitted to the hospital with upper Gl bleeding. Upper endoscopy demonstrated an ulcer with adherent clot at the GE junction. Bleeding resolved and the patient underwent follow-up endoscopy as an outpatient. There appeared to be Barrett's mucosa present and biopsies of the previous ulcer site were obtained. These were interpreted as showing focal high grade dysplasia and were repeated shortly thereafter. The patient ultimately underwent a surgical procedure.

Gross Pathology:

An esophagogastredomy was received in three parts. The proximal stomach showed a normal mucosal fold pattern. A segment of distal esophagus, 3.0 em in length, showed a superficially ulcerated roughened tan mucosa. A second 1.2 em long segment of more proximal esophagus showed a uniform gray-tan mucosa without gross abnormalities.

Submitted Material:

1. H & E stained slide «< of the distal esophagus

No imaging studies available


Case#7

Case contributed by: Erik VanOs, MD; Laura Pomeranke, MD; Brock Vickery, MD; Mike Sherwin, MD Penrose-St. Franlcls Health Service, Coloraod Springs, Colorado


This 68 year old female with a history of diabetes and hypothyroidism was initially evaluated for persistent epigastric pain with EGO, abdominal ultrasound and HIOA scan. She was noted to have a decreased ejection fraction and underwent an uneventful laproscoped cholecystectomy. Her abdominal pain continued and 50 lbs of weight loss were noted. Thorough evaluation including colonoscopy, repeat EGO, CT abdomen all failed to reveal an explanation. Uver function tests were normal. She was referred for ERCP and was noted to have a stricture in the proximal 1/3 of the common bile duct with irregular margins, suspicious for malignancy. Brushings were performed and she subsequently underwent surgery.

Gross Pathology:

A 1.6 em long by 1.0 em diameter segment of hepatic duct. Sectioning perpendicular to the duct revealed irregular sclerotic areas around the duct lumen extending into the adjacent fat.

Submitted Material:

1. H & E stained slide ((b of the hepatic duct.


Case#7

Case contribl.rted by: Er:ik VanOs, MD~ Laura Pomeranke, MD: Brock Vickery, MD; Mike Sherwin, MD Penrose-St. Franicis Health Services, Colorado Springs. Colorado

Figure 1: ERCP


Case contributed by: Sam Rubinson, MD; Doug Franquemont, MD Penrose-St. Francis HeaHh Services, Colorado Springs, Colorado


Case#8

A 72 year old female with a history of hypertension underwent colonoscopy to evaluate an episode of rectal bleeding which had occurred three weeks previously. At 8 em from the anal verge was a 3-4 em diameter polypoid mass. The exam was otherwise unremarkable. Multiple biopsies of the mass were obtained and the patient ultimately underwent a surgical procedure.

Gross Pathology:

Received in the frozen section room was a 2.0 x 1.7 x 1.2 em polypoid mass with a suture marking the resection margin. The margin was inked and the mass serially sectioned .perpendicular to the margin.

Submitted Material:

1. H & E stained slide~ of the rectal mass.

Penrose Canoer Conference 1998

Case conuib\lted by; Sam Rubinson. MD; DO\Jg Franquem<>n~ MD Penroae~St. Francis Health SeMces, Colorado Springs, Colorado

Case #8

Figure 1: View of Rectum


Case Contributed by: Kyung-Whan Min, MD and Frederick Carson, MD Baptist Medical Center of Oklahoma

and Deaconess Hospital, Oklahoma City, Oklahoma


Case #9

A 42 year old otherwise healthy male with intermittent melena and anemia. Upper and lower endoscopic evaluations were both unremarkable. Because of continued Gl bleeding another upper endoscopy was performed and this time a "lesion" was identified and cauterized. Occult bleeding continued and a repeat colonoscopy was negative. An upper Gl series was performed and a mass in the proximal jejunum was identified. ACT scan of the abdomen demonstrated an 11 em diameter complex cystic and sol id mass involving the proximal jejunum just below the ligament of Treitz. The patient underwent surgery.

Gross Patholqoy:

An en-bloc resection of proximal jejunum with adherent distal jejunum and descending colon contained a lobulated gray-tan mass 9 x 6 x 6 em. The tumor grossly involved the jejunal wall and extended into the intestinal lumen. The mucosal surface showed a central crater-like area of ulceration.

Submitted Material:

1. H & E stained slide IIIIJ of jejunal mass


Cose contrii>U1ed by- t(JII~g-Whan Min. MD and Frederick Carson. MD Bapbst Medical Center of Oklahoma

and Oeii<>OOOSo Hoopl1al. Oklahoma City, Oldahoma

Case#9

Figure 1: Single Small Bowel Image


Case oontnbllted by: Kyung-Whan Min, MD and Frederic~ Carson. MD BaptiSt Medical Center of Oklahoma

and Oeaeones• Hosp~al , Oklahoma C~. Oklahoma


Case#9



Case #10

Case Contributed by: Erik VanOs, MD; Doug Clark, MD; Paul Anderson, MD and Tobias Kircher, MD Penrose-St. Francis Health Services, Colorado Springs, Colorado


A 57 year old male with a history of alcohol abuse and alcoholic liver disease was admitted to the hospital with hematemesis. Urgent upper endoscopy demonstrated esophageal varicies which were not bleeding and oozing from a poorly defined site in the duodenum. Bleeding stopped with cautery. Hepatitis profile was ordered and returned positive for hepatitis C antibodies. Abdominal pain led to an abdominal ultrasound which demonstrated a 4 em irregular mass in the left lobe of the liver. A follow-up CT scan was performed and a diagnostic procedure followed.

Gross Pathology:

A percutaneous needle biopsy of the liver was received in Hollandes fixative.

Submitted Material:

1. H & E stained slide fiJJ# or photomicrographs of the liver biopsy


Case#10

Case conllib<Jied by. Erl< VanOs. MD; Doug Clorl<. MD; Pa<A Anderson, MD and Tobias KircheJ, MD Peruose-St. Ftancis Health SeMen, Co4onldo Sp(ongs, Colorado




Case #11

Case Contributed by: James.G. Smith, MD; Brock Bordelon, MD; Doug Franquemont, MD Penrose-St. Francis Health Services, Colorado Springs, Colorado


A 53 year old female with a 25 year history of ulcerative colitis underwent surveillance colonoscopy and biopsies. Three years prior to this exam, surveillance biopsies had demonstrated "very mild focal dysplasia." The biopsies from the current exam returned demonstrating "mild to moderate" dysplasia. This prompted a repeat colonoscopy with more biopsies 3 months later.

Gross Pathology:

Endoscopic biopsy samples taken at 10 em intervals from throughout the colon were submitted in Hollandes fixative.

Submitted Material:

1. H & E stained slide otfJ; of the recto-sigmoid biopsy.


CaM contributed by: Jamu G. Smilh, MD: Broclc BO<delon, MD; Doug Franquemont, MO Penros&-St. Francis Hnlth SeMc:es. ~ Spring•. ~

Case #11

Figure 1: Barium Enema Image


Case #12

Case contributed by: Buck Patel, MD; M. Setty, MD; and Doug Franquemont, MD Penrose-St. Francis Health Services. Colorado Springs. Colorado


A 71 year old male was admitted to the hospital with a recent fall, 25 lbs weight loss and rectal bleeding. Colonoscopy demonstrated an ulcerated, friable mass in the rectum 10 em from the anal verge. Multiple biopsies of the mass were obtained. Laboratory revealed total bilirubin 1.4 mg/dl, SGOT 68 U/L, and alkaline phosphatase 331 U/L (nl 33-117). Further radiologic studies were. performed.

Gross Pathology:

Multiple rectal biopsy samples up to 3 mm in maximum dimension were received in Hollandes fixative.

Submitted Material:

1. H & E stained slide~ or photomicrographs of the rectal biopsy.


Case eontrlbutod by: Buck Patel, MD; M. Setty, MD; and OOUll Franquemont, MD Penrose-St. Francis Hea~h Services. Colorado Sp~ngs. Colorado

Case #12

Figure 1: Pelvic CT

August 5, 1998

Juan Rosai, M.D. Department of Pathology Memoria l Sloan-Kettering 127.5 York Avenue New York, NY 10021

Dear Dr. Rosai:

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719J76.SS 16 PhonC" 719.776.2108 rax

M. Uerthrnng. f\•1.0 . 0, Fr.lnqutmont, M.D. J. flegslrom, M.O. 'f. Ki•·chl!t'1 M.O~ n. y \.,':Shc, M.D C>.C. M.,ycs, M.D. G.H. M()orc. t\·1.0. E.M. Nobl!!s, 1\l.O. C.G. S<iOIIo, M.D .• PI,,(}, 1(, M. Sh-.!rwil\, M.D.

Greetings from Colorado and the Department of Pathology at Penrose Hospital. · we are in the final stages of preparation for the 1998 Penrose Cancer Conference which will be held again at the Broadmoor Betel on September 18 and 19, 1998. You. have so kindly served as a con~ultant for previo~s Cancer Conference slide sets, and we are asking .that you once aga·in honor us by serving as an expert reviewer of these cases. Enclosed please find a set of the B&E glass slides and kodachromes accompanied by the syllabus for the conference. These are the same materials which e.ach of the participants attending the conference wil l receive. Please return your diagnoses on these 14 h i stopathologic samples {12 patients) to me on or befos e Friday,

""'J~!""!~~~· A stamped self-addressed envelope i s .1.nci'uded wl.'t!it ~ final diagnoses.

Thank :~ou in advance for once again helping us to prepare for what I believe will be an outstanding conference with Dr. Rodger Haggitt from the University of Washington· Department of Pathology serving as our pathology discussant for GI and hepatobiliary tumors. I look forward to hearing from you.

Enclosure

TK/mh

Tobias Kircher , M.D.

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September 2, 1998

Director, Department of Pathology and Laboratory Medicine

Penrose-St. Francis Health Services 2215 N. Cascade Avenue Colomdo Springs, CO 80907-7699

Dear Dr. Kircher:

Tha nk you very much for sending me a slide set of the Semina r on GI pathology that you will be having at the Penrose Cancer Hospital later this year. These are my diagnostic impressions on the cnses.

Case 1

The lesion of the ampulla ofVaLer (of which I have a slide labelled "1") has the appearance of a villous adenoma with high-grade dys plasia/ adenocarcinoma in situ. The lesion from the pancreas (of which I have three kodachrome slides) has the typical appearance of a pancreatic endocrine neoplasm (islet cell tumor) of one type or another. The lesion from the liver (labelled "#2") shows a malignant tumor for which my differential diagnosis is between hepatoce llular carcinoma ancl a metas tasis ft·om the pancreatic endocr ine neoplasm. I slightly favor hepatocellula r carcinoma because of the large ahe of the tumor cells, the abundant granular eosinophilic cytoplasm, and the sinusoida l pattern of growth, but a n immunohistochemical study is obviously needed in order to categorize the tumor properly.

I hope you do not mind, but I must say tha t I found the labelling system used for the seminar a little confusing. Would it not have been better to label

illrmorial Sltkm-Kmering Cmll'trC<'Illrr 12n l6rk Arnlllt. Nl!lt•lOrl:. Ntu· }1,rk 10021

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these two slide!; simply "lA" and " lB," so that the slide· numbers for the subsequent cases would have matched the numbers of those cases?

Oase 2

There is-a small lymphocytic infiltrate in the lamina propria of the stomach, which I think is consistent with a small lymphocytic lymphoma of the socalled MALT type. I hope that Dr. Haggitt will discuss whether it is appropriate to call these lesions malignant, or whether we are dealing with a "lymp.homa imaginaire;" as shaTply pointed out in a recent editorial (Hmu Pathol 29:769, 1998).

Case 3

The section from the stomach (slide 4) is a smooth muscle tumor which I would call a leiomyoma, although I suspect that Dr. Haggitt will call it GIST, in keeping with eurren t terminology. The lesion i n the tail of the pancreas is a classic cystadenoma of the so-called microcystic, serous, or glycogen-rich type.

Case 4

I believe that this .is an example of intra-abdomina] fibr omatosis (desmoid tumor). Because of tlle location of th.is tumor, the patient sho.uld be investigated for Gardner syndrome.

Case 5

This is a predominantly if not exclusively intraductal papillary carcinoma associated with extensive mucin production resulting in a mucocele-like effect. This lesion should not be confused with mucinous cystadenoma or mucinous cystadenocarcinoma.

Case 6

This is a well to moderately-differentiated adenocarcinoma arising at the gastmesophageal junc~iOil, presumably from Barrett's mucosa, and haying a few 'foci of squamous metaplasia. Dr. Haggitt will have a field day with this case.

Case 7

I think this is an extremely well-differentiated adenocarcinoma of the extrahepatic biliary system. Furthermore, I have the impression that the lymtJhoid tissue nodule present at the periphery of the slide and encased in fibrous tissue is a lymph .node containing metastatic carcinoma. The

appearance of this area is similar to Fig. 14-24B on page 9.61 of the 8Lh edition of Ackerman's Surgical Pathology (Hl96).

Case 8

I favor in this case the diagnosis of well-differentiated mucin-pt·oducing adenocarcinoma ~;~rising in a villoglandular polyp, rather than the phenomenon of so-called localized colitis cystic profunda in a polyp, because of the atypia of the epithelium associated with. the mucinous lakes in the submucosa.

Case 9

The fact that this tumor is located in the wall ofthe jejunum suggests a neuroendocrine nature for it, but the presence of innumerable well-formed rosettes makes me think that this tumor belongs to the category of extraskeJetal Ewing's sarcoma/PNET/peripheral neuroepitheli.oma. A most peculiar and spectacular .case.

Case 10

This looks like a well-differentiated hepatocellular carcinoma to me, both in the slide and in the kodachrome.

Case 11

T would bl;lve designated this slide as carcinoma in situ, rule out invasion, agains t a background of chl·onic ulcerative colitis, and would have recoll1Illended a colectomy.

Case 12

I .suspect that there· is a tumor he1·e, but the material is too scanty for me to be more specific.

'l'hank you for having sent me this material. I am looking forward to 1·eceiving the discussions and diagnoses from Dr. Haggitt.

Best personal regards,

~ Juan Rosai, M.D.

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October 14, 1998

Juan Roeai, M.D. Department of Pathology Memorial Sloan-Kettering 1275 York Avenue New York, NY 10021

Dear or. Roeai:

Ctutur:. l't1thOiogy A)ttOCi.:at(), 1'.C. 2215 N£'1 th c,)f.c,ldl• A\ l'I\Ul'

Col01'.ll1" :;pri •'~"· (\"'lor.ldo I'I{)IJ(J7 -7f~ 719 776.58lo l'hO<>< 719 776 2108 F."

M . 8crth.rong.. M.O. D. Fr.mqlU·monl, M D J. }lc-g:.trum, M 0. T. Kitl'h.:·r. M 0 . U. L.awsh~. M 1). D.C. ~tavpo;, M U G.~l Moore, M.O E.~1. Noble.·:., f\•1 0 . C.G. Sciuttn, M D., r h.O ~. M. Sherwin. M.l) .

Thank you very much for serving as a consultant for the recent 1998 Penrose Cancer conference on Gaatrointeatinal and Bepatobiliary Tumors. The conference was a great success with excellent audience-preaentor interaction. Your diagnoses were greatly appreciated and added to the diecuaeion of each of the caeea. 1 have enclosed for your interest a copy of Dr. Haggitt's diagnoses on each of these cases and the slides which he used for his discuesion.

Enclosure

TK/mh

1

DIAGNOSES - CASE 1

• Familial adenomatous polyposis coli (FAP)

• Adenocarcinoma of ampulla of Vater

• Islet cell carcinoma of pancreas with eventual metastasis to liver

Penrose CancerCont 1·1

Penrose Cancer Conference

EXTRACOLONIC MANIFESTATIONS OF FAP

• Adenomas in stomach, small intestine (ca also) • Fundic gland polyps of stomach • Mesenteric fibromatosis ·Osteomas • Multiple endocrine neoplasia syndrome (I & II) • Carcinoma of : thyroid, gallbladder. bile ducts. liver • CNS neoplasms • Congenital hypertrophy of retinal pigment

epithelium (CHRPE) ~-c:..'""

RELATIVE RISK OF UPPER Gl CANCER IN FAP'

No. 95% ConfidlJnce Sit• Carcinoma RR Um#s p

Duodenum 7 ~J1 132. 681' <0.001 Ampulla 4 124 34.317 <.0.001 Gastric 2 2.4 0.29 - 9 NS Non-duodenal 12.7 0.32 . 71 NS

'e..uedOfl tl:ltlow·upor 1,39\ pali&tllt (18.e7Q Pl-'11') Fro:n: Olfe•,•v~ GJ.6.. '''ol G;1.s~m.~ 19lll, 102; 19!0.

-.-..c-.~ .....


EXTRACOLONIC ADENOMAS IN FAP

Stomach Duodenum Papilla of Vater Jejunum Ileum

9-50% 50-100% 55% 40% 20-55%

Frcm; H'99i:l a~ Reid. AmJ Svrg P~rhOf 1986;10:871

ENDOSCOPIC BIOPSY OF AMPULLARY NEOPLASMS

• Forceps or snare Bx used • Multiple Bx obtained (ave 4)

• Diagnosed on first biopsy • Diagnosis on 2nd or 3rd Bx • Diagnosis made at surgery • Carcinoma ·diagnosed on

endobx

36/44

6/44 2144

16/18

82%

95% (cum) 100% (cum) 90%

From; Komorowtik.i RA, c1 al. Am J $1119 Porh0/ 1991;15:1188 --~(iON!·$

DIAGNOSIS - CASE 2

Low grade polymorphic 8-cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma)

Penrose Car.oer Cont 2-1

P.enrose Cancer Conference

PRIMARY Gl NON-HODGKIN'S LYMPHOMA

B Cell Malt type (low or high grade) IPSID (low or high grade, + alpha HCD) Mantle cell (lymphomatous polyposis) Others, corresponding to lymph node

equivalents

Teen Intestinal T -cell lymphoma + enteropathy Olhers -

l-t .. C$01't HIJt1tPath011994,25:t02Q """·•-c:.w.tl>l

HISTOLOGIC FEATURES OF MALT LYMPHOMA

• Multifocal • Dense lymphoid infiltrate • Diffuse. marginal zone or lnterfollicular

growth pattern • Small, cleaved lymphocytes • Lymphoepitheliallesions • Destruction of glands • Dutcher bodies

• Few blasts: high-grade = 10 % •---~

RELATIONSHIP OF H. PYLORI TO MALT LYMPHOMA

• Normal stomach - no lymphoid follicles

• H. pylori infection - lymphoid follicles (100%)

• 90% + H. pylori in MALT lymphoma

• H. pylori Infection precedes lymphoma

• Eradication of H. pylori causes regression of some low-grade MALT lymphomas ._t_e.., ..


CLINICAL CHARACTERISTICS OF MA LT LYMPHOMA

• Predominately older age group • Predominately antrum • Symptoms suggest gastritis/ulcer • Usually localized at dx (stage IE or liE) • Indolent course, slow to disseminate • Prognosis more favorable than

eqwvalent nodal disease for both lowand high-grade _ , _ _ .,

H. PYLORI AND GASTRIC LYMPHOMA

Location No. % Casas % Controls Odds Lymphoma Patients Infected lnlsctecl Rallo

(95% Cl)

Gastric 33 85 55 6.3 (2.0-20)

Non-gastric 31 65 59 1.2 (0.5-3.0)

___ ,.

H. PYLORI IN MALT LYMPHOMA

• H. pylori stimulates cultured lymphoma cells

• Response T-cell dependent

• T -cell response to H. pylori strain-specific

DIFFERENTIAL DIAGNOSIS OF GASTRITIS AND MALT LYMPHOMA

MALT Gastritis L ymp/Jorrn>

Follicles + + Dense extra. +

folllc lnfllttata Ex\rafollic SCL + LEL Rare + Moootypic lg

Surface + , Cytoplasrruc 40% Clonal by F!CR 15% 70% TrisomyJ 60% 1(11:18) 40%

----~··>·•

DETECTION OF CLONAL lgH GENE REARRANGEMENT BY PCR IN GASTRIC

BIOPSIES WITH DENSE L YMPHOIIllNFILTRATE

Monoclorlal in 9113 (69%) cases wi1h histologic lymphoma Monoclonal in 2155 {4%) cases histologically negative • .. . the histologic assessment. of ~astric biopsies remains the method of chOice for the ttfagnosts.of tymphOma i.n gas trio. endoscopic bioP.sies With a dense mucosal lymphoid infiltrate. PCR Provides a uSef~,j; leC:hniqu$ to sl.ippor1 the diagnosis if donal BIJlpfiftCBtion products are fol6ld. •

PROGNOSIS OF GASTRIC MALT LYMPHOMA VERSUS NUMBER OF

BLASTS (CHEMO OR RAD Rx)

No blasls

1-10% blasts, diffuse

Clusters of blasts, but < 1%

10% blasts or more

10 yr SuNival

90%

75%

No effect

High grade

From Oe.Jong o. es 81, GtUt!OO!tletoJCgy 1997:112~1~ -·-~CMOJ• >I

Penrose Canc_er Conference

DETECTION OF CLONAL lgH GENE REARRANGEMENT BY PCR IN

CHRONIC H. PYLORI GASTRITIS

Monoclonal in 6 of 41 (13%) patients 5 of 6 had LELs (1 or 2)

10 aCiditional patients had LELs without clonality

'' ... a diagnosis of gastric low-grade B-cell MALT lymphoma should not be based solely on the filiding of a monoclonal gene rearrangement by PCR.'

Hsi: eo, e1 at Hum l>athot t996;27:290

OUTCOME OF GASTRIC MALT LYMPHOMA FOLLOWING

ERADICATION OF H. PYLORI

Complete regression (CR) 12122 54% Partial regression 5/22 23% No response 5/22 23% Limited to mucosa/submuc, CR 12/14 86%• M. propria and beyond 0/10

·cR m;ry 1ike morrttll to develop; many remain PCR• F"rom: Stt-k.mam M. et at GaStroi ntero!Ogy 1997;1 t3:1087. _.,_.,. .. ..,,

•

DIAGNOSES - CASE 3

• Gastric stromal tumor

• Microcystic cystadenoma of pancreas

Penrose Ct ncer Col\f 3·1

•


PROPOSED PREDICTORS OF MALIGNANCY IN GISTs

• SiZe

• Mitotic count

• Cellularity

• Necrosis

• lnvasitm of lamina propria

• Absence of organoid pattern/skeinoid fibers in small Intestinal ones

--ewtt

PREVALENCE OF MALIGNANT Gl STROMAL TUMORS BY SITE

Esophagus Stomach Duodenum Jejunum/ileum Rectum GIST rare in colon

%Malignant

Nil 20% 50% 60% 80%

Gl STROMAL TUMORS: TYPICAL IMMUNOHISTOCHEMISTRY

V"NII Des Ac/ln S-100 CD34 Nonnal gut SM + • Esophagus + • Arising in MM. any site - • • Stomach' + • • +

Small bowel' + • • +

'Rttvllt varitblo. occulonany negatlva tor V, A, 5-100 (one or motl!~: cytokerali'n po.sHivily rf!aY ooeur; nwttl m•ntttt rnay N positil.·e ISci\Wilnnoma). - ... e--...


•

PREDICTORS OF MALIGNANCY IN GISTs

Site Size Mitotic count

Stomach > 6.0 em >5/50 HPF

Duodenum ~4.5cm >2150 HPF

Jejunum/ileum >7.0cm >5150 HPF

Colon/rectum Not published yet

Ftom: GOldblum JR. et tl, Am J Su19 P1tft0/1ttS:tt:71 and T'MOre.k JA, et at Mod Pfth011997:10:.200

HISTOGENESIS OF Gl STROMAL TUMORS

• Smooth muscle

•Interstitial cells of Cajal

• Nerve sheath cells

• Others (lipomas, MFH, etc) ____ ._.

IMMUNOPHENOTYPE OF GIST

Antibody

Vimentin c-kit (kit receptor) C034 PGP 9.5 (neural cell marker) a•smooth muscle actin Muscle specific actin Desmin S-1 00 Protein

%Positive

100 100

72 71 15 0 0 0

Ftom: KlncibiOM L-G, cl al Am JPtUIOI1991;157: 12S9 - .. ~ .. Cou.~t

INTERSTITIAL CELLS OF CAJAL (ICC)

• Found between enteric plexus and smooth muscle of Gl tract

• Have a pacemaker function

• Express CD34 (myeloid progenitor cell antigen, also expressed in endothelium, some other mesenchymal cells)

• Express c·kit proto-oncogene

• Modified smooth muscle cell (?)

CARNEY'S TRIAD

• Gastric epithelioid leiomyosarcoma

• Pulmonary chondroma

• Functioning extraadrenal paraganglioma

---~·•or

Gl STROMAL TUMORS IN AI,DS AND ORGAN TRANSPLANTATION

• Occur in children • Stomach, duod, small bowel, colon • Multiple • Benign and malignant • May be associated c multiple pulmonary

leiomyomasileiomyosarcomas • Associated with clonal EB virus

..L4MA ;990;263:3182 and NEJM t995;332:12 and 19


c-kit PROTO-ONCOGENE

• Encodes a tyrosine kinase receptor (KIT)

• Ligand is stem cell factor receptor (SCF)

• SCF-KIT interaction essential tor developmerjt of melanocy~es, RBCs, germ cells, mast cells, and ICCs

• Gain of function mutation found in GISTs and mastocytosis

• Germline mutation in familial GISTs

CARNEY'S TRIAD

• Six of 24 patients (25%) had complete triad, remainder 2 of 3

• Tumors tend to be multi'ple • Tumors occur at a young age (16 years

average) • Mostly females F:M=12:1

• Leiomyosarcomas tend to have an indolent course

From: Catney JA. Mtdieint 1983:62>\59 ·-..c--~n

MICROCYSTIC ADENOMA OF THE PANCREAS: CLINICAL FEATURES

• Occurs predominately in elderly (mean age 65+)

• Female predominance (70%)

• Usually presents with abdominal pain or mass (2/3): may be asymptomatic (1/3)

• May obstruct - jaundice and/or pancreatitis

• May erode into duodenum - Gl hemorrhage

MICROCYSTIC ADENOMA OF THE PANCREAS: PATHOLOGIC FEATURES

• Discrete. usually solitary mass • Equal distribution In head, body, and tail

• Multilocular c smal cysts; occasionally oligocystic

• Central scar(! calciflcabons) often present • Cysts lined by cuboidal to flat. clear cells • Glycogen present mucin absent

• No cytologic atypsm • EM and ICC: epithelial cells

......... ~-- .. ··


MICROCYSTIC ADENOMA OF THE PANCREAS: BIOLOGY

• Derived from centroacinar cell • Benign with rare exceptions

• Found In 72% of patients with VH-L diSease (retinal angiomatosis, cerebellar hemangioblastoma, renal cell carcinoma, pheochromocytoma, renal & pancrealic cysts)

• VH-L tumor suppressor gene on chromosome 3p • VH-L LOH in 70% of spo<adic microcyslic

adenomas

DIAGNOSIS - CASE 4

Mesenteric fibromatosis

Penrose Ca neer Cont • ·1

•


CLASSIFICATION OF FIBROMATOSES

• Superficial fibromatoses Palmar, plantar, penile, knuckle pads

• Deep fibromatoses • Extraabdominal • Abdominal wall • lntraabdominal (mesenteric, pelvic)

IMMUNOPHENOTYPE: GIST VS MESENTERIC FIBROMATOSIS

Antibody GIST MF Vlmentin + + Desmin Sm muscle actin + • Sm muscle myosin HC C-kit + CD34 +(50%)

--~--

MESENTERIC FIBROMATOSIS: BIOLOGY

• Local recurrence 40% +

• More aggressive in FAP

• Malignant transformation exceedingly rare

• Trisomy 8 and other chromosomal abnormalities common

• May respond to sulindac. tamoxlfen, chemotherapy

Penrose Cancer Conferenc.e

MESENTERIC FIBROMATOSIS: DIFFERENTIAL DIAGNOSIS

• Gl stromal tumor

• Fibrosarcoma

• Nodular fasciitis

• Reactive fibrosis

MESENTERIC FIBROMATOSIS: CLINICAL FEATURES

• Occurs at relatively young age (mean -40)

• More common in women (3:1 or more}

• 10-15% have FAP; 10-15% of FAP patients have mesenteric fibromatosis

• Usually affects mesentery of small bowel - obstruction

-~-a·

•

CASE 5 - DIAGNOSIS

Intraductal papillary mucinous tumor (I PMT} of the pancreas

Penrose cancel COtlf 5-1

Penrose Cancer Conference.

SPECTRUM OF CYSTIC TUMORS OF THE PANCREAS

Mucinous cystadenocarcinoma 27 40%

Serous cystadenoma 18 26% Mucinous cystic neoplasm 15 22% Solid and cystic neoplasm 3 4% Cystic islet cell tumor 2 3% lntraduetal papillary mucinous tuma< 2 3% Cystic teratoma 1 1.5%

From Wat5hirit AL et el. Ann Swv IH0;212:• 32 __ c..r,.t

IPMT- TERMINOLOGY

• Intraductal mucin - hypersecreting neoplasm, mucinous ductal ectasia, mucin-producing tumor

• Intraductal papilloma, villous adenoma, intraductal papillary neoplasm

• Koppel, 1994 - intraductal papillary mucinous tumor (IPMT) ---.....

DIFFERENTIAL DIAGNOSIS: IPMTVS MCN

Female predominance Often located in tail

IPMT MCN +

+ Discrete, multiloculated mass + Communication with duct system +

Ovarian-like stroma + Estrogen & progesterone receptors +


IPMT

• Ohhashi, 1982 -"mucous secreting pancreatic cancer"

• Diffuse dilation of main pancreatic duct with filling defects on ERCP

• Extrusion of mucin through enlarged papilla of Vater

IPMT- WHO CLASSIFICATION

• Benign: Intraductal papillary mucinous adenoma

• Borderline: Intraductal papillary tumor wl!h moderate dysplasia

• Malignant Intraductal papillary mucinous carcinoma Papillary mucinous carcinoma

--~··

IPMT ·MOLECULAR MARKERS

..... G_ IOQI!Gia -- """'' ... --· ......... KoQI fft.ltlll.cn orJ (0%) 10i12 '13") Ut (1DCJIW..) 10t11 (911Ji) p5l OVef·

txprtuioft 013 (0%) 011t tcm) OIC C~) 1111 (64%)

o-M)B-2 over· •~prenlon

lr.l (33!4) 4111 (36~) 114 (25~) 5111 (45%)

Cyctn 0 1 over- ~ (100%) 71t1 (84%) 21$(40"') 7/11 (64%) tJIIPftJ..on

•

CASE 6 - DIAGNOSIS

Adenocarcinoma arising in Barrett's esophagus


IS IT BARRETT'S OR NORMAL COLUMNAR EPITHELIUM IN THE

ESOPHAGUS?

• Normal individuals may have columnar epithelium in the distal esophagus due to a Z-line that is irregular, or which lies entirely within the distal esophagus.

, _ t_ CoMj. J

HOW MUCH METAPLASTIC EPITHELIUM IS NEEDED TO

DIAGNOSE BARRETT'S?

• When no endoscopically visible segment of Barrett's is present, the significance of a few metaplastic glands detected microscopically is unknown

• Avoid diagnosis of Barrett's, use "Focus of metaplastic columnar epithelium."

NEOPLASTIC PROGRESSION IN BARRETT'S ESOPHAGUS

Chronic GastrCJ,!lllophageal Reflux

Es6{hagitis =

Metaplastic C~mnar Epithelium =

Dy$fasia -Adeno~rcJnqma ·-'-""''


BARRETT'S ESOPHAGUS

DEFINITION

Metaplastic columnar epithelium, defined by acid mucin-containing goblet cells, in esophagus.

---<:;.oti•J

COLUMNAR EPITHELIUM IN THE ESOPHAGUS

Fundic or cardiac. distal 2cm

Metaplastic, any length

Cardia·c, more than 2· em Fundic, upper esophagus

Cancer Diagnosis Risk Normal

Barrett's +++ esophagus Columnar lined • (?)

Inlet patch +

DYSPLASIA

DEFINITION

Neoplastic epithelium confined within basement membrane of gland within which it arose

GRADING SYSTEM FOR DYSPLASIA

• Negative • Indefinite

• Positive Low-grade High-grade

Mod.ilicd trom 190/0MSG HIJfTI P•ltlol1983;14:931 - .. -.._ ...

INTEROBSERVER AGREEMENT: BARRETI'S ESOPHAGUS

Negative 71%

Indefinite vs, dysplasia 76%

HGD+ IMC 86% •

From: Reid BJ. til al Hum Parho/ 1988;19:166 ........ ~ _..(:.oof .. ,

"MARKERS" REPORTED IN BARRETI'S DYSPLASINCARCINOMA

"M!Jrker" Status Prognostic

Value DNA aneuploidy + + 4N f,G21tet) traction t + Pro 1leratlon index t ~~~ muUdel

muUdel DCC muUdel MCC muUdel Rb muUdel

........ c-c •• o .. ,T


DYSPLASIA: PROBLEMS

• Sampling • Distinction from reactive/

regenerative change • Subjective interpretation • Observer variation • Natural history unknown (time

course? reversible?} ~ ... c.-e..• ...

FOLLOW-UP OF HIGH-GRADE DYSPLASIA IN B.ARRETI'S

ESOPHAGUS

- Follow-up. months-No. Mesn

COOrs• Patients (SO) Median Range HGD-+CA' i5 (26%) 27 (15) 24 12·72

HGO-+HGD .27 (47%) 24 (22) 12 4-71

HGD- <HGO 16 (27%) 40 (25) 43· 4-89

~>o:...;.i:_ ......... ,

"MARKERS' REPORTED IN BARRETI'S DYSPLASINCARCINOMA (Cont'd)

'Marke(' p16 c-myc H·ros ~rb B2 bcl-2 TGFa EGFR Sucrase-isomaltase

Prognostic Status Value muVdel

overexpressed mutated

overexpressed overexpressed overexpies.sed overexpressed overexpressed -... ~ ......... ,

CASE 7 - DIAGNOSIS

Adenocarcinoma of common bile duct ( cholangiocarcinoma)

Penrose Canotl Conr 7.1


CHOLANGIOCARCINOMA

• No sex predilection; mean age -60 yrs • Increased incidence in:

PSC/UC Clomorchis sinensis Infection Congenital abnormalities of ducts

• Location Intrahepatic (least common) Extrahepatic: upper 1/3 • 50 to 75%;

middle 1/3 -10 to 25%; lower 1/3 = 10 to 20% - t -•t-IM

CYTOKERATIN 7/'20 IMMUNOPHENOTYPE OF CHOLANGIOCARCINOMA VS OTHER

AOENOCARCINOMAS

CK7•1CK20+ CK7•1CK20- CK7-ICK20+ CJ<7-ICK2Q-

ChOiangloca Pancreatic ca Trans eel ca Ov""f

(mocinoos)

Breast Colorectal lung Ovaty (serous) Endomenium


Hepatocellular Renal ProstatiC Smalcel

"'""" .. c:-·-'··

CARCINOMAS WITH SIMILAR HISTOLOGIC APPEARANCES

Adenocarcinoma of: • Intrahepatic ducts • Extrahepatic ducts

• Gallbladder · Pancreas

• Combined hepatocellular/ cholangiocarcJnoma

• Melastatic

DIFFERENCES BETWEEN HEPATOCELLULAR CA AND INTRAHEPATIC

CHOLANGIOCARCINOMA

Cell of origin Cirrhosis a -fetoproteln B1le Mucin Mode of spread

HCC Hepatocyte

• •

+or ..

Venous

IHC

Bile duct cell

+ Lymphatic

•

CASE 8 - DIAGNOSIS

Adenocarcinoma arising within a colorectal adenoma

PentOSe Cancet Coni .. ,


STEPS IN MANAGEMENT

• Establish presence of invasive CA

• Determine depth of invasion

• Assign histologic grade • Search for vascular invasion

• Evaluate completeness of resection • Estimate risk of metastasis

- t-- •l

FACTORS SAID TO INCREASE PROBABILITY OF POSITIVE

NODES

• Invasion into submucosa of bowel wall

• Poorly differentiated tumor

• Vascular invasion

• Cancer at polypectomy margin

•

DEPTH OF INVASION VS POSITIVE NODES

Depth of lnv8sion

Submucosa M. propria Through m.p.

% PositivB Lymph Nodes

Morson Minsky Grigg (2084) (1 68) (268)

11 12 58

0 28 39

6.5

All rectal cancers; all resected by LAR or APR -·-~tooi!U


QUESTION

Is this carcinoma a T1N0M0 (Dukes' A) or is it really a T 1 NxMx?

-··<-~··

LEVEL OF INVASION AND PRESENCE OF POSITIVE NODES

L8V81 of Invasion

0

1-3

Postive Nodes (44 resections)

0/18

0/13

Dead of Disease

0/65 0/36

4 3/13 (23%) 4/28 (14%) ~.only wei Of t'I'IOdeta!dly dil'iere:nll:l!'ecl tutnoq Wflnout l)mgNtic; kwaiJOft H19;.e AC. es at. G~ lttS~It~l

DEPTH OF INVASION VS POSITIVE NODES

T1, all cases T2, all cases T 1, no vessel invasion· T2, no vessel invasion T2, grade 1 "lVI Of 8VI

11 PosNodes

3126 28/128

0/15 20/ 104

0/9

%

12 22 0

19 0

From 8roc:lk.ty IT, eu J.. C• nur 1992;69·322 - .. co.-'"'"w

CA IN ADENOMA- COMPLETENESS OF EXCISION VS OUTCOME

Excision Complete 4...-3

37 Polypectomy only

..._ Resection- no CA

Excision Doubtfully Complete

Excision 11 .- 1

Incomplete -....10

Polypectomy only

Resection (for poMy diff CA)

Polypectomy only

R . _8NoCA

esect•on-2 CA at site ' o CAIn nodes __ ...,._.

INDICATIONS FOR COLECTOMY CARCINOMA ARISING IN AN ADENOMA

• Poorly differentiated tumor

• Vascular Invasion

• Positive polypectomy margin II endoscopist uncertain of completeness of excision

N .. ft Hone •• -~ • I'UirrM'It for eacft PoJlicnt mt.lM 1M ptMirled on ., IIWMduel basa.

•

CARCINOMA WITH SUBMUCOSAL INVASION 100 PATIENTS- SURGICAL

RESECTION

2 Die from surgel'( 96 Survive surge I'(

5 P!sitive nodes J ---- 3 Die from cancer

2Cured

THUS 100 operations. 2 pabents cured 5 dead - 2 from surgel'(. 3 from cancer 5 Would have d1ed 1f no operations do'J!!..,_ . .... ,.


CA IN ADENOMA· STATUS OF EXCISION, VENOUS INVASION AND OUTCOME

_.- 49 A&W (16 VI) . • ....- 61 NoRx - 90ead.unrelated(3)

ExCISion ~ - 3 Dead CA" Complete........_ 1 Resection- A&W •

10 No Rx - 9 A&W (4) Excision / -~ Dead recurrence Incomplete'., ·

8 Resection- All A&W (5) •1 HUMII'IIO c:ecMm.A. 2 tlt't~t ot u!U;nown ori;h.

ffOI'I'. Ger8gheyM.c:t• Gutt99t:»n4 -<--...

·OPERATIVE MORTALITY COLORECTAL CA

Fielding. 1989

Glass. 1986

Mayo Clinic, 1976

<70 yrs >70 yrs

Mortality

3% 12%

3.2%

2.0%

CARCINOMA WITH SUBMUCOSAL INVASION 100 PATIENTS - SURGICAL

RESECTION

96 Survive surgel'( 2 Die from surgery

10 Jositfve nodes ___ _ J 5 01e from cancer

4 Cured

THUS 100 operations. 4 patients cured 8 dead- 2 from surgery, 6 from cancer 10 Would have died If no op8flltions d'l!J.~.~~·"

CAUTION I

If segmental resection is planned because submucosal invasion was present in polypectomy specimen -all parties, including the patient, must be aware that there is a 90 to 95 percent chance of finding no cancer in the resected specimen.


CASE 9 - DIAGNOSIS

Peripheral neuroectodermal tumor (PNET)

Penrose C..neer COnf 8·1


PERIPHERAL NEUROECTODERMAL TUMOR

• Adolescents or young adults

• Soft tissue of lower ext or paravetebral regfon, other

• Aggressive, met to lung and bone

• Closely related to Ewing's sarcoma (t 11 :22; CD99} ---·J

IMMUNOPHENOTYPE- CASE 9

CD99 CEA NSE CK CGA GFAP

•

+ + (by report}

"Borderline" (by report)

--CioN ...


DIFFERENTIAL DIAGNOSIS - PNET

• Ewing's sarcoma

• Rhabdomyosarcoma

• Neuroblastoma

•Lymphoma

IMMUNOPHENOTYPES OF PNET AND HISTOLOGICAllY SIMILAR ENTITlES

Antibody VIM CK NF S100 NSE C099 ACT DES LCA

PNET • + + + + + !: + -ES • + + + RMS + + + + • + - - -NB + + +

LYM + • - .. c-~H

DIAGNOSES - CASE 10

• Chronic hepatitis C

• Cirrhosis

• Hepatocellular carcinoma

Penrose cancer Cont to-1

•


IMMUNOHISTOCHEMISTRY FOR DIFFER·ENTIATING HEPATOCELLULAR

FROM OTHER CARCINOMAS

lmmunophenotype Sensitivity (%) Specificity (%) pCEA canancular + 79 97 u-fetoprotein (AFP) + 57 97 HepPar 1 + 82 90 AFP <1r pCEA + 90 97 AFP or pCEA .or HepPar 1 t 100 88

f rom:" Mlnc-.rvinl MI. eta!. Mtid Parho/1997;10:686. -.. ,-~, .. ,

ALBUMIN MESSENGER RNA BY IN· SITU HYBRIDIZATION IN

HEPATOCELLULAR NEOPLASMS

# #Pos %Pos

Hepatocellular carcinoma 23 22 96 Hepatocellular·aaenoma 7 7 100 Hepatoblastoma 3 3 100 Hepatoid area,. germ 2 1 50

cell neo. Other carcinomas 47 0 0 ftom. Kri$hno1 M, el al. AmJ ~19P1thot 1997;21:1.£7

- ... e-Ciloo~•

HIOLOGIC FACTORS IN HEPATOCELLULAR CARCINOMA

• Hepatitis 8 , C · Alcohol • Genetic hemochromatosis

• <:<'1 antitrypsin deficiency ·Aflatoxin • Thorotrast (discontinued)

• Anabolic and <;ontraceptive S!!':.~!1t,(?,?)


IMMUNOPHENOTYPE VS HEPATOCELLULAR CARCINOMA

DIFFERENTlATION

/mmunophenolype Well Diff ModDiff Poorly Diff

HepPar 1 + 100% 90% 50% AFP+ 0 44% 83% pCEA+ 100% 80% 50%

From; Minervini MI. el al. Mod PI/hoi t99'7:10,BB4.

TWO TYPES OF HEPATOCELLULAR CARCINOMA*

lmmunophenotype

HepPar+ AE1/AE3 or CK~9 +

239/290 85/290

'No.cases had c:bolanglocarcinoma ditlerentiatlon. Ftom~ Wu P•C, etal, .AmJPIIU'IO.I -1996;1.t9l1167

(99.7%)

(29.3%)

CLASSIFICATION OF CHRONIC HEPATITIS.

• Viral (Hepatitis B, B+D, C) • Autoimmune hepatitis • Chronic hepatitis, unclassified as to viral or

autoimmune (cryptogenic} • Drug-induced • Wilson's disease • a-1·antitrypsin deficiency • Primary biliary cirrhosis • Autoimmune cholangitis • Primary sclerosing cholangitis

--(-e.t!l0.1

CHRONIC HEPATITIS: CHANGING TERMINOLOGY

Old Terms • Chronic active hepatitis

• Chronic persistent hepatitis

• Chronic lobular hepatitis

• Problems: false prognostic implications ar:1d not reproducible

-e-..c..t iH

CIRRHOSIS: CHANGING TERMINOLOGY

Old Terms • Portal cirrhosis • Postnecrotic cirrhosis • Posthepatitlc cirrhosis • Laennec's cirrhosis • Nutritional cirrhosis

f rom: 9ans ano Ludw.g Am J Surg Pamon995: 19: t409 ....... ""'~ .. """' ' ~''

RISK FAClORS ASSOCIATED W~TH HEPATITIS C (USA)


CHRONIC HEPATITIS: CHANGING TERMINOLOGY

New Terms • Chronic hepatitis due to hepatitis B, C,

other, with: mild, moderate or marked activity

• Activity based upon extent of: • portal inflammation • pie.cemeal necrosis • lobular degenerationlnecrosis • fibrosis -· .. ~-~···· ...

CIRRHOSIS: CHANGING TERMINOLOGY

New Terminology • Cirrhosis due to hepatitis B, C, other

• With mild, moderate or marked activity

• With monoacinar or multiacinar regenerative nodules

• With or without hepatocellular ca

MAGNITUDE OF HEPATITIS C IN UNITED STATES

HEPATITIS C ·150,000 cases/yr

Sympto~ Asymp\omatic ~inant 40,000 (27%) 110,000 (73%) hepatic failure

\ . / 500 (0.3%) Chronic 'hepatitis

75,000 (50%)

c ;rrtiosls 15,000 (10%)

........ ,_~·· •O-• •

HEPATITIS C AND A LCOHOL

Alcohol use of more than 10glday:

• Leads to more severe liver disease • Higher frequency of cirrhosis • Increased serum hepatitis C viral RNA • Interferon therapy less effective • No difference in histology

•


CASE 11 - DIAGNOSES

Colonoscopic Biopsies - . Ulcerative colitis with high-grade dysplasia

Colectomy-

•

Well differentiated adenoca invading into submucosa; 23 neg nodes

Pen10se Cancer Cont 1 1·1


OPTIONS FOR MANAGING THE CANCER RISK IN ULCERATIVE COLITIS

• Ignore it

• "Prophylactic" colectomy

• Colonoscoplc surveillance for dysplasia/early carcinoma

--O.OOO it.-1

NEOPLASTIC PROGRESSION IN ULCERATIVE COLITIS

Inflammation ---"":::7' Dysplasia

Carcinoma --~· ...

GRADING SYSTEM FOR DYSPLASIA

, ·Negative

• Indefinite

• Positive Low-grade High-grade

Mo<llfltd rrom tBOJOMSG Hwn PtMo/ 19BJ;t4:i31 -.. ,-~,,,.

1rose Cancer Conference

RISK FACTORS FOR CARCINOMA IN ULCERATIVE

COLITIS

• Extent of disease

• Duration of disease

• Age at onset

Primary sclerosing cholangitis

Presence of dysplasia

No relationship to activitv "-c-~· ...

DYSPLASIA

DEFINITION

Neoplastic epithelium confined within basement membrane of gland within which it arose

DETECTION/DEVELOPMENT OF CANCER IN ULCERATIVE COLITIS BASED ON INITIAL

BIOPSY HISTOLOGY

Diagnosis on lnjtial Nc DBve/oped No. IMth Biopsy PatltntJ Dysplasia Cofecromy Ct~rcinoma

Dysplasia IS (18) 15 7 lndernte 20 5 3 1

NegatiVe 175 6 • 0

TOTAlS 213 29 22 8

ftom Nu9&fd FW, et 11 G~IOfnb"o..oW 199 1~t~~foo<ol ••·•

DYSPLASIA: PROBLEMS

• Sampling • Distinction from reactive/

regenerative change • Subjective interpretation • Observer variation

• Natural history unknown (time course? reversible?)

--·---"''

RECTOSIGMOID PREDOMDINANCE OF COLORECTAL CARCINOMA ASSOCIATED

WITH ULCERATIVE COLITIS

SMlor Author Riddell Hughes Plior Mlr·Modjle"l leHg TOTAL

Anatomical Locarico of Colorectal ca R$ D TAlC

50% 20% 22% 8% 47% 6% 22% 25% 61% 6% 24% 9% 48% 8% 20% 24% 62% 8% 16% 13% 52% 12% 21% 15%

DYSPLASIA-ASSOCIATED LESION OR MASS (DALM)

Co/onoscoplc &ppeBfiJI>Ce

Qegreeof Lesion or mass Flat mucosa dysplasia Number Cancer Number Cancer

Severe 2 2 1 MOderate 5 2 6 Mild 5 3 20 1 TOTAL 12 7 (58%) 27 1 (4%)


BIOPSIES REQUIRED FOR ADEQUATE SAMPLING - HISTOLOGY

Histologic Category Jndefimte Dysplasia Csncer

No. Bx for 90% con5dence No. Bx lor 95% confidence

29

49

33

56 64

From: Rubin Ce. eur. Gs.sttoentsrofoOY 1tt2,.103:HI11 .......... , ...... c;. ..... ,

INDICATIONS FOR COLECTOMY: DYSPLASIA IN

ULCERATIVE COLITIS

· Consensus panel: Any dysplasia

• Conventional wisdom -High-grade dysplasia - Multifocal low-grade dysplasia - Dysplasia in a visible lesion

IS THE MASS DYSPLASIA IN UC OR A SPORADIC ADENOMA?

Proximal unaffected mucosa;

Affected mucosa

Sporadic adenoma

Pedunculated. no Sporadic adenoma dysplasia in stalk or elsewhere: Sessile: Cannot differentiate

... -c-..-···•J

HOWEVER

• If the lesion can be demonstrably completely resected, and

• If there is no dysplasia anywhere else,

• Careful follow-up may be considered

PATHOLOGISrS PROBLEMS

Technical quality of specimens Orientation (clinician?) Fixation Step serial sections Staining

Interpretation Know what is not dysplasia Familiarity witlli'eactlve/regenerative changes

Communication with clinician ___ ....._.


REQUIREMENTS FOR AN EFFECTIVE DYSPLASIA SURVEILLANCE PROGRAM

Clinician Identify high-risk patient early Select optimal time for biopsy (activity) Adequacy of endoscopy and biopsy sampling Assume responsibility for patient compliance

Pathologist Technical quality of biopsies Interpretation of biopsies

Patient - Compliance -·'-""""

•

CASE 12 - DIAGNOSIS

Large-cell neuroendocrine carcinoma of rectum

Pe-nros~ C•noei Conf 12·1

PeJJiose Cancer Conference

COLORECTAL NEUROENDOCRINE CA: IMMUNOPHENOTYPE

Antibody Positivity Cytokeratin 100% EMA 85% NSE 72% Chromogranin 25% Synaptophysin 25% From: G•trey MJ. etal AmJSt.f'OPJIJ'JtN ttiO:t4:tOt0 -.. ~~"''

NEUROENDOCRINE CELLS IN COLORECTALNEOPLASMS

• Carcinoids

• Neuroendocrine carcinoma

• Composite carcinoma/carcinoid

• Adenoma/carcinoma ---....

CHARACTERISTICS OF COLORECTAL NEUROENDOCRINE

CARCINOMA

• Most common in cecum, rectosigmoid

• Many (62%) associated with adenoma

• Usually advanced at time of diagnosis (83% Stage 3/4 vs 35%')

• Prognosis extremely poor From: Gaffey MJ. tt at AmJ SUI'}PIIflof 1990:14:1010,

----~~··


CASE 12: IMMUNOPHENOTYPE

Antibody

Cytokeratin EMA NSE Synaptophysin S100 LCA

Immunoreactivity

+ +

CLASSIFICATION OF NEUROENDOCRINE CARCINOMA

OF THE COLON & RECTUM

• Small cell neuroendocrine • oat cell variant

• Small cell neuroendocrine · Intermediate cell variant

• Moderately differentiated neuroendocrine carcinoma

general information history of the - rosai's collection of ... · general information history...

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