acquired pure red cell aplasia ( prca ) is a rare , generally chronic condition of profound anemia characterized by a severe reduction in the number of reticulocytes in the peripheral blood and the virtual absence of erythroid precursors in the bone marrow .
these include : 
 drugs - phenytoin , trimethoprim , zidovudine , chlorpropamide , recombinant erythropoietin , and mycophenolate mofetilinfections - parvovirus b19 , hiv , and viral hepatitisautoimmune disorders - systemic lupus erythematosus , rheumatoid arthritis , hemolytic anemia , and allogeneic stem cell transplantlymphoid malignancies - chronic lymphocytic leukemia , large granular leukemia , non - hodgkin lymphoma , hodgkin lymphoma , and myelomamyeloid malignancies - chronic myeloid leukemia , myelofibrosis , and prodrome of myelodysplastic syndromeother causes - thymoma , pregnancy , idiopathic , etc . 
 
drugs - phenytoin , trimethoprim , zidovudine , chlorpropamide , recombinant erythropoietin , and mycophenolate mofetil infections - parvovirus b19 , hiv , and viral hepatitis autoimmune disorders - systemic lupus erythematosus , rheumatoid arthritis , hemolytic anemia , and allogeneic stem cell transplant lymphoid malignancies - chronic lymphocytic leukemia , large granular leukemia , non - hodgkin lymphoma , hodgkin lymphoma , and myeloma myeloid malignancies - chronic myeloid leukemia , myelofibrosis , and prodrome of myelodysplastic syndrome other causes - thymoma , pregnancy , idiopathic , etc .
a number of cases of coexisting myasthenia gravis ( mg ) and prca have been described in the literature ; all were thymoma associated except for one with thymic hyperplasia .
as the onset of anemia in prca is insidious , patients may have little signs and symptoms until the anemia becomes severe .
extreme pallor or decreased exercise tolerance may be the first sign of this disorder in a previously healthy individual .
bone marrow examination shows normal overall cellularity , with complete or virtually complete absence of red cell precursors . there is a well - documented association of prca with thymoma , with an incidence of about 5% .
even if a thymoma is present , surgical resection only occasionally results in improvement or cure of the prca , and additional treatment ( e.g. , glucocorticoids , cyclosporine , and cyclophosphamide ) is needed in most cases . even though it is not very common to have acquired prca , documenting its etiology needs extensive and systemic workup , which involves multispecialty approach .
we are reporting a similar case who was treated outside our hospital for many years with blood products and hematinic and later got documented thymoma as an etiological cause .
a 60-year - old gentleman , who was normotensive , nondiabetic , and euthyroid , presented to our outpatient clinic with features of symptomatic anemia in the form of malaise and poor exercise tolerance .
there was no history of apparent blood loss , bleeding diathesis , or poor intake .
there was also no history of muscle weakness , diplopia , speech fatigue , or any surgery .
he gave a history of repeated blood transfusions , ten such events he could remember and was on iron supplements since 6 years . on clinical examination , he had severe pallor and mild splenomegaly , rest of examination was unremarkable . on evaluation ,
he had hemoglobin of 2 g / dl with normal red cell indices and raised serum iron indices [ table 1 ] .
his liver function test , kidney function test , lactate dehydrogenase , electrolytes , calcium , and phosphorous were normal .
bone marrow aspiration was done , which revealed hypercellular marrow with absent erythroid precursors , abundant iron stores with normal other cell lines [ figure 1 ] .
laboratory parameters of patient bone marrow revealing absence of erythroid precursors hepatitis b , c , and a was negative as was epstein 
connective tissue disease markers such as antinuclear antibody , dsdna , and rheumatoid factor levels were normal .
contrast - enhanced computed tomography ( ct ) scan was done which showed large anterior mediastinal mass with close approximation to great vessels [ figure 2 ] .
then , ct - guided biopsy of mass was carried out , which was consistent with who class b1 thymoma [ figure 3 ] .
further immunohistochemistry was carried out , which revealed ck 5/6 positive in plump oval cells , terminal deoxynucleotidyl transferase , and cd3 positive in lymphocytes and ki67 of 50% [ figure 4 ] .
( b ) contrast histopathological examination ( hpe ) of anterior mediastinal mass revealing small oval to spindle cells admixed with lymphocytes consistent of who type b1 thymoma immunohistochemistry revealing thymoma positive for ck5 , cd3 , and ki67 is 40% as for as management was concerned , prca is treated with steroids or immunosuppressants , but some patients go into remission on surgery only .
patient was not a surgical candidate as he would have persisted with gross residual disease , so we put this patient on multiagent chemotherapy with cisplatin , adriamycin , and cyclophosphamide .
plan is to give four cycles of chemotherapy followed by surgery with or without adjuvant radiotherapy .
prca , a disorder first characterized in 1922 , is a syndrome characterized by severe normochromic , normocytic anemia associated with reticulocytopenia and absence of erythroblasts from an otherwise normal bone marrow .
the acquired form of prca presents either as an acute self - limited disease , predominantly seen in children or as a chronic illness that is more frequently seen in adults .
as was seen in our patient , he also presented with chronic anemia , had got multiple blood transfusions till we received him .
depending on the cause , the course can be acute and self - limiting or chronic with rare spontaneous remissions . in approximately 60% of patients with prca ,
their serum and its igg fraction inhibit the growth of patient and normal erythroid progenitors in vitro .
the target antigen is usually not known ; in a few cases , however , the igg fraction contains an inhibitor of erythropoietin .
in other cases of autoimmune prca , suppression of erythropoiesis seems to be mediated by t - lymphocytes . in our patient
the net result of the immune attack in prca , which is characterized by marked reduction or absence of all recognizable red cell precursors in the bone marrow and absence of reticulocytes in the peripheral blood . in our patient , net hemoglobin was 2.0 g / dl with normal red cell indices and almost absent reticulocytes in peripheral blood and absent erythroblasts in bone marrow .
mg appears in about 20%40% of patients with thymoma , and prca develops in about 2%5% of those patients . on the other hand ,
thymoma is detected in 10%17% of patients with mg and in 5%13% of patients with prca .
however , the simultaneous occurrence of mg , prca , and thymoma is extremely rare . in our patient ,
chest x - ray had mild mediastinal widening , but ct showed large mediastinal mass with close relation with large arteriovenous system .
as per the who histological classification , thymoma is divided into six types as type a , ab , b1 , b2 , b3 , and c. our patient had b1 histology pattern , consisting of lymphocytic rich predominantly cortical organoid cells .
it has been seen that type a is associated with prca and type b with mg , but in our patient , this correlation was not seen .
patient was inoperable at beginning , and likely fitted in clinical stage ii to iii and complete surgical excision was not possible .
hence , our patient was put on chemotherapy at outset and plan is thymectomy after few cycles of chemotherapy .
it has been seen that prca improves in 30% of patients after complete thymectomy , and complete surgical excision with adjacent structures is possible in 88% of patients .
there are several options for inducing remission of prca after surgery , but many patients with acquired prca require immunosuppressive therapy to maintain remissions .
corticosteroids , cyclosporin a , and cyclophosphamide are almost equally effective for inducing remissions of prca , but the most important difference between these agents is the feasibility of long - term maintenance .
considering the recurrent nature of acquired prca , it has been suggested cyclosporin a as first - line therapy for these patients at a dose of 2.53 mg / kg twice daily to achieve trough cyclosporin a ( csa ) levels of 150250 ng / ml for a maximum of 34 months . this trough csa level has been empirically determined according to a consensus from a multicenter randomized study in japan for aplastic anemia .
prognosis of thymoma is related to stage of presentation , presence or absence of complete resection , and histological subtype .
subtype a and ab behaves as benign tumor , subtype b ( b1 and b2 ) behaves as low - grade tumor , and subtype b3 and c behaves as thymic carcinoma .
 pure red cell aplasia ( prca ) is a known entity in clinical medicine . 
 patients are often transfusion dependent for their whole life . 
 ascertaining its etiology is always a herculean task . 
 we received a similar transfusion - dependent patient , who on evaluation was found to have thymoma as an etiological factor . 
 thymoma presenting as prca is seen in 2%5% patients and evaluating prca for thymoma is seen in 5%13% patient . as per the who histopathological classification , 
 thymoma has six types and type a is associated with prca and type b is associated with myasthenia gravis . 
 this correlation was not seen in our patient , who had type b thymoma . 
 surgical resection of thymus improves 30% of prca and rest needs immunosuppression . 
 our patient was not the surgical candidate , and hence he was put on chemotherapy . 
INTRODUCTION
CASE REPORT
DISCUSSION AND REVIEW OF LITERATURE
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