1993(9) : 114-117

CASE REPORT

Anterior Mediastinal Exenteration for Thymoma Associated with Pttre Red Cell Aplasia S o l o m o n Victor, T. Sunder, S. Sethttraman

A 4 6 - y e a r - o l d f e m a l e h a d t h y m o m a

a s s o c i a t e d w i t h p u r e r e d ce l l a p l a s l a , a

r e l a t i v e l y u n c o m m o n e n t i t y . A n t e r o l a t e r a l

t h o r a c o t o m y in s u p i n e p o s i t i o n o f f e r e d

e x c e l l e n t e x p o s u r e f o r e x e n t e r a t i o n o f an-

t e r i o r m e d i a s t i n u m . S t e r o i d s a n d cyc lo -

p h o s p h a m i d e w e r e a d m i n i s t e r e d p o s t o p -

e r a t i v e l y . She r e m a i n s s t a b l e one y e a r a f -

te r s u rg e r r . The in c i d e n ce, clln ical f e a tu res,

p a t h o l o g y , p a t h o g e n e s i s , m a n a g e m e n t a n d

p r o g n o s i s o f t h y m o m a w i t h p u r e r e d ce l l

a p l a s t a a r e r e v i e w e d .

hypoce l lu l a r with marked se lec t ive e ry th ro id sup- press ion and spar ing of mye lo id lines. Megakaryo- cytes were seen . E ryh rocy te s e d i m e n t a t i o n rate (ESR) was 74mm in first hour . P r o t h r o m b i n time was 13 ( con t ro l 12) s e c o n d s , ac t iva ted partial t h r o m b o p l a s t i n t ime 31 (con t ro l 30) s e c o n d s and f ib r inogen level 255mg%. I m m u n o l o g i c a l investi- gations were as follows: IgA 124mg%, IgM 186mg%, C3 164mg% andC4 38mg%. R h e u m a t o i d factor, c ryoglobul ins , a u t o a n t i b o d i e s such as an t inuc lea r a n t i b o d y and anti d o u b l e s t r anded DNA a n t i b o d y were absent . X-ray chest r evea l ed a medias t ina l mass p r o t r u d i n g into the left hilar r eg ion (Figl) .

T h y m o m a assoc ia ted with pure red cell aplasia (PRCA) is rare. Hence , a fu r the r case is , ' epor ted.

A 46-year -o ld lady p r e s e n t e d with p rogres - s ively increas ing d y s p n o e a . Physical examina t i on was no t c o n t r i b u t o r y e x c e p t for marked pa l lo r and haemic mt, rmur o v e r the p reco rd ium.

Her h a e m o g l o b i n was 3.6 g%; per ipheral smear s h o w e d hypoch romia , microcytosis , macrocytosis , an i socy tos i s , occas iona l sch izocy tes and poly- ch roma t i c cells with r ed t i ced e ry th rocy t i c den - sity. Re t icu locyte coun t was on ly 0.01%. Her red cell ind ices were as fo l lows: MCV 107 cu ram, MCH 36 pg and MCHC 34%. P la t e l e t s a n d l e u c o c y t e s w e r e n o r m a l . B o n e m a r r o w was

From the tleart Institute, Madras, India.

Address for correspondence : Dr Solomon Victor, Director, The Heart Institute, 15, East Street, Kilpauk Garden Colony, Madras 600 010, INDIA

Fig 1. X-ray chest reveals mass protruding into the left hemithorax.

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VICTOR et al Thymoma with red cell aplasia

CT scan of the thorax de l inea ted an anterior mediastinal mass 4.8 cm x 3.7 cm x 5 cm, dipping into the middle mediast inum.

Prior to surgery, her haemoglobin level was raised to l l g % with the transfusion of packed cells. A left anterolateral thoraco tomy in supine position revealed an encapsula ted anter ior medi- astinal tumour arising from the left lobe of the thymus which could be easily enuc lea ted (Fig 2). Anterior mediastinal exentera t ion was per formed removing all anter ior mediastinal tissue including the opposi te lobe of thymus. No nodes were seen. Her pos topera t ive recovery was unevent fu l and haemoglobin at time of discharge was 13g%.

Grossly, the tumour was a partly encapsu- lated, firm mass measuring 4.7 cm x 2.2 cm x 0.5 cm, fleshy tan in colour. There were focal areas of h a e m o r r h a g e on s e c t i o n i n g the lef t lobe . Histopathological examinat ion revealed a partly encapsulated tumour composed predominant ly of sheets of epithelial cells mixed with lymphoid cells. There was no cytological atypia. The cap- sule was thick and was seen to divide the tumour into lobules. There was no perineural or capsular invasion. The appearances were suggestive of benign thymoma. The right lobe measuring 3 cm x 1 cm x 0.2 cm showed thymic tissue with no specific lesion. Anterior mediastinal tissue was composed of ad ipose tissue with no ectopic thymic tissue or secondary deposits .

Fig 2. Good exposure of the tumour and its pedicle through anterolateral thoracotomy in supine position.

When rev iewed two months later, her haemo- globin was 6.3 g% and PCV 19%. Reticulocyte

count was only 0.2%. Peripheral b l o o d smear

revealed the presence of microcytic, hypochromic red cells. Platelet and let icocyte counts were normal. Marrow was cellular with normal mega- karyocytes and white cell lines. There was marked suppress ion of red cell precursors. No abnormal cells were seen. ESR was 35 mm in the first hour . She was transfused two units of b lood. Steroid t he rapy was c o m m e n c e d with p r e d n i s o l o n e 1 mg /kg /day for four weeks. Folate supplements were added.

She r e tu rned four w e e k s later with the haemoglob in level at 5.2 gO, PCV 20% and reticu- locyte count 0.1%. She was t ransfused four units of b lood . Cytotoxic immunosuppressan t therapy with cyc lophosphamide was given in addit ion to steroid therapy. The dose of cyc lophosphamide was 50 mg, 100 mg and 150 mg daily for ten days each. The dose was reduced to 100 mg daily in the next ten days, 50 mg daily for ano ther ten days, and 50 mg on alternate days for six weeks. Steroids were s tepped down and s topped at the end of about three months. Monthly estimations of haemoglobin were consistent ly above 10 g%. She required no further b lood transfusion.

When reviewed a year after surgery, she was doing well. Her haemoglob in level was 12 g%.

D i s c u s s i o n

Thymomas, the most common tumours in the an te rosuper ior mediast inum, comprise about 20 per cent of all mediastinal masses in adults. I Myasthenia gravis is the most common associated disease occurring in abou t 30-50 per cent of patients with thymoma. 2-4 Other associated dis- ea ses i n c l u d e PRCA, C u s h i n g ' s s y n d r o m e , hypogammaglobinaemia , dermatomyosit is , sys- temic lupus erythematosis , rheumato id arthritis, Sjogren's syndrome and ulcerat ive colitis 2.4.

Although the associat ion of thymoma with anaemia was recognised by Matras and Priesel in 1928, as quo ted by Hirst and Robertson, s the first acceptable report of thymoma with PRCA is as- cribed to Opsahl in 1939. s,6 By 1983, Dessypris, quo ted by Marmont, s r epor ted about 150 cases of th~rmomas and PRCA. PRCA occurs in about 3-5 per cent of patients with thymoma 8 while about 30-50 per cent of adults with PRCA have associ- ated thymomas. 6.9 This highlights the close rela-

t ionship be tween the two entities, despi te the

Indian Journal of Thoracic and Cardiovascular Surgery Volume 9; Number 2: December 1993

rarity of PRCA. There appears to be a significant preponder-

ance of females 6'1~ over males (2-3:1) after 40 years of age. This entity usually presents with anaemia, the diagnosis of associated thymoma usually first seen on x-ray being incidental. How- ever, in some cases the anaemia manifests during the investigations of thymoma or even after thymectomy for thymoma, s In about 30 per cent of patients, leucocytes and platelets may also be depressed along with red cells. 4

Thymic tumours are subclassified 4 into the following types:

i. Lymphocytic, when more than 80 per cent of the cells are lymphocytes.

ii. Epithelial, when more than 80 per cent of the cells are epithelial cells.

iii. Mixed, when both cell types occur in equal proportions.

A variant of thymic epithelial cell is the spindle cell. the above classification is important in that there are differences in the association of various tumour types with au to immune diseases. Thus, PRCA is more frequently seen with the spindle cell variant of thymoma, 7,9 while myasthenia gravis is more frequently seen with the lymphocytic su b type ) In the presence of red cell aplasia, Masaoka e t a l 9 noted all the 17 cases of thymoma in their series to be of spindle cell type; while Hirst and Robertson 5 reported 33 patients with mixed cell type and eight with spindle cell type in their series of 56 patients. Our patient had mixed cell t y p e of thymoma.

The mechanism of PRCA in patients with thymoma is not clear. It is perhaps immunologi- cally mediated. Red blood cells develop from totipotent-systemic colony forming unit (CFU-S) to mature erythrocytes via erythroid burst form- ing unit (BFU-E), erythroid colony forming unit (CFU-E) and erythroblasts. Erythroprotein stimu- lates CFU-E, while interleukin-3 (IL-3), secreted by T cells, stimulates BFU-E thereby promoting erythropoiesis.

Antibodies reacting against erythroprotein, erythroid progenitor cells and erythroblasts have been detected in patients with PRCA. 6 Also, cel- lular inhibitory mechanisms such as decrease in IL-3, increase in suppressor T cells, increase in

gamma-interferon which inhibits BFU.E and CFU- E, may cause anaemia3 Viral aet iology has also been implicated as a probable cause which may separately induce PRCA and thymic neoplasm. 9

After correcting anaemia with haematinics and b lood t r ans fus ion , t h y m e c t o m y is the treatment of choice. It is followed, if required, by s t e r o i d s , 5'9-13 i m m u n o s u p p r e s s i o n , s'~'14 splenectomy s,6,1~ or plasmapheresis3 '14

Hirs t a n d R o b e r t s o n -~ p o i n t o u t t ha t thymectomy was first described by Humphries and Southworth in 1945 for this syndrome with complete remission of the anaemia. The most widely used approach to the resection of thymoma is median s ternotomy ~ which offers an excellent exposure. Simple thymectomy with resection of intracapsular thymus is easily done. It also per- mits e x t e n d e d t h y m e c t o m y wi th e f fec t ive exenteration of all ectopic thymic tissue. 4,9 How- ever, Masaoka e t a l 9 noted no difference in the r e su l t s b e t w e e n s imp le a n d e x t e n d e d thymectomies.

Anterolateral thoracotomy in supine position provided adequate exposure for this operation. Complete excision of the thymic tumour, the opposite thymic lobe and anterior mediastinal tissue could be easily performed. This approach should be especially suited for cases with lateral extension of the growth.

In selected cases, video assisted thoracoscopic resection has been a t tempted successfully, xs thereby avoiding open surgery and its a t tendant morbidity.

Thymectomy as a sole therapeutic procedure brings about remission in 20-30 per cent of cases. 4,6 However, steroid therapy is usually started 4-8 weeks after thymectomy, when there is no remis- sion.S.14 Of the seven patients with steroid therapy after thymectomy in Hirst and Robertson series, s three had good remission. Masaoka e t a l 9 re- viewed 16 patients after thymectomy in their series of 17 patients. Most of them responded favourably to steroids. Schmid e t a l ~~ recorded six instances of remission following steroid therapy after thymectomy among 27 patients. Parry e t a ~ 2

cite an instance where anaemia responded to steroids after thymectomy. Jacob e t a ~ 3, noted remission in two out of 12 such patients. Our patient did not respond even to steroid therapy

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VICTOR et al Thymoma with red cell aplasia

after t h y m e c t o m y and i m m u n o s u p p r e s s i v e t he rapy

had to be ins t i tu ted . I m m u n o s u p p r e s s i o n ~ is c o n s i d e r e d w h e n

there is no r e s p o n s e to bo th t h y m e c t o m y and s t e ro ids . B io log ica l i m m u n o s u p p r e s s a n t s l ike a n t i - t h y m o c y t e g l o b u l i n and cy to tox i c i m m u n o - s u p p r e s s a n t s l ike c y c l o s p o r i n A, a z a t h i o p r i n e and

c y c l o p h o s p h a m i d e h a v e b e e n u s e d . TM

R a g h a v a c h a r .6 n o t e d 65 pe r cent r e m i s s i o n in

cases of a c q u i r e d PRCA with c y c l o s p o r i n A. In res i s tan t cases , s p l e n e c t o m y has b e e n t r ied

with va ry ing resul ts . 5'6'~4 P l a s m a p h e r e s i s a ims at r e m o v i n g lgG a n t i b o d y . M a r m o n t 7 n o t i c e d re- s p o n s e in five ou t o f n ine pa t i en t s so t rea ted , wi th long te rm r e m i s s i o n s in two cases .

Overa l l , the r emis s ion rate wi th v a r i o u s t reat-

m e n t m o d a l i t i e s is a b o u t 25-30 pe r cent . Rare in s t ances of s p o n t a n e o u s r emis s ion of PRCA wi th

t h y m o m a are on r e c o r d : 7 P r o g n o s i s d e p e n d s on the s tage o f the dis-

ease . H i s to log i c f ea tu re s of p r o g n o s t i c va lue have no t b e e n c l ea r ly iden t i f i ed . Some a u t h o r s s'~8 r epor t wor se p r o g n o s i s wi th p r e d o m i n a n t l y epi - thelial t u m o u r s wi th the e x c e p t i o n of s p i n d l e cell var iant . Batata et aPSrepor t a d e c r e a s e d surviva l rate in t h y m o m a s wi th p a r a n e o p l a s t i c a b n o r m a l i - ties. Masoaka et a l ~ po in t out that t h y m o m a s wi th

PRCA c o m p r i s e the p o o r e s t p r o g n o s t i c g r o u p in t h y m o m a b e c a u s e PRCA is re f rac tory .

R e f e r e n c e s

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4. McKenna WG, Bonomi P, Barnes MM, Glatstein E. Malignancies of the thymus In Roth JA, Ruckdeschel JC, Weisenburger TH, eds, Thoracic Oncology. Philadelphia, WB Saunders; 1989: 466-73.

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13. Jacobs EM, Hutter RVP, Poor JL, Ley AB. Benign thymoma and selective erythroid aplasia of the bone mar- row. Cancer 1959; 12: 47-57.

14. Krantz SB. Acquired pure red cell aplasia In Hoffman R, Benz EJ Jr., Shatill SJ, Furie B, Cohen HJ, eds, Hematology: Basic Prnciples and Practice. New York, Churchill Livingstone; 1991: 180.

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