Purna A. Kurkure

Trisal et al
adjuvant abdominopelvic radiation with or without myeloablative
chemotherapy with stem cell rescue have been reported to improve
survival in DSRCT, although cure remains elusive in widespread disease.9 More effective therapeutic options including targeted therapies
focusing on cellular regulatory mechanisms and pathways for this
tumor need to be explored to improve outcome and reduce treatment
related toxicity. In this case, contemporary curative treatment has
been offered and in view of the localized disease a favorable outcome
is expected.
Sajid S. Qureshi
Pediatric Surgical Oncology Services, Tata Memorial Centre, Bombay, India
Mukta R. Ramadwar and Seethalakshmi Viswanathan
Department of Pathology, Tata Memorial Centre, Bombay, India
Ashish V. Bakshi and Brijesh Arora
Department of Pediatric Oncology, Tata Memorial Centre, Bombay, India
Tejpal Gupta and Siddharth Laskar
Department of Radiation Oncology, Tata Memorial Centre, Bombay, India
Seema S. Medhi
Department of Radiodiagnosis, Tata Memorial Centre, Bombay, India
Mary A. Muckaden
Department of Radiation Oncology, Tata Memorial Centre, Bombay, India
Shripad D. Banavali and Suresh K. Pai
Department of Pediatric Oncology, Tata Memorial Centre, Bombay, India
Sangeeta B. Desai
Purna A. Kurkure
Department of Pediatric Oncology, Tata Memorial Centre, Bombay, India
© 2007 by American Society of Clinical Oncology
The author(s) indicated no potential conflicts of interest.
1. Gerald WL, Rosai J: Case 2: desmoplastic small round cell tumor with
divergent differentiation. Pediatr Pathol 9:177-183, 1989
2. Gerald WL, Miller HK, Battifora H, et al: Intra-abdominal desmoplastic small
round-cell tumor. Report of 19 cases of a distinctive type of high-grade polyphenotypic malignancy affecting young individuals. Am J Surg Pathol 15:499-513,
3. Biswas G, Laskar S, Banavali SD, et al: Desmoplastic small round cell tumor:
Extra abdominal and abdominal presentations and the results of treatment. Indian
J Cancer 42:78-84, 2005
4. Chang F: Desmoplastic small round cell tumors: Cytologic, histologic, and
immunohistochemical features. Arch Pathol Lab Med 130:728-732, 2006
5. Rodriguez E, Sreekantaiah C, Gerald W, et al: A recurring translocation,
t(11;22)(p13;q11.2), characterizes intra-abdominal desmoplastic small round-cell
tumors. Cancer Genet Cytogenet 69:17-21, 1993
6. Lee SB, Kolquist KA, Nichols K, et al: The EWS-WT1 translocation product
induces PDGFA in desmoplastic small round-cell tumour. Nat Genet 17:309-313,
7. Ito E, Honma R, Imai J, et al: A tetraspanin-family protein, T-cell acute
lymphoblastic leukemia-associated antigen 1, is induced by the Ewing’s sarcomaWilms’ tumor 1 fusion protein of desmoplastic small roundcell tumor. Am J
Pathol 163:2165-2172, 2003
8. Wong JC, Lee SB, Bell MD, et al: Induction of the interleukin-2/15 receptor
beta-chain by the EWS-WT1 translocation product. Oncogene 21:2009-2019,
9. Lal DR, Su WT, Wolden SL, et al: Results of multimodal treatment for
desmoplastic round cell tumors. J Pediatr Surg 40:251-255, 2005
DOI: 10.1200/JCO.2007.11.9487
Department of Pathology, Tata Memorial Centre, Bombay, India
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Thymoma-Associated Severe Aplastic Anemia
Treated With Surgical Resection Followed by
Allogeneic Stem-Cell Transplantation
A 44-year-old man presented with chronic cough not resolving on antibiotic treatment, and was found to have a large anterior
mediastinal mass on chest roentgenogram. Computed tomography demonstrated a 15 cm ⫻ 10 cm ⫻ 13 cm mediastinal mass
beginning at the level of the innominate veins extending to the
right anterolateral chest wall with displacement of the mediastinum and some compression of the superior vena cava (Fig 1). The
spleen was slightly enlarged, and there was no lymphadenopathy.
WBC count was 10,600/cc, hemoglobin 11.8 mg/dl, and platelet count
5,000 ⫻ 109/L. Differential count showed 15% polymorphonuclear
leukocytes, 84% lymphocytes. Lactate dehydrogenase was within normal limits. Phenotype of peripheral blood demonstrated 96% lymphocytes and T cells, with a predominance of CD8-positive cells. Flow
study demonstrated 98% CD2 positive, 96% CD3, 97% CD5, 98%
CD7, 84% CD8, CD10 was negative as were CD19, CD20, CD23,
FMC-7, and kappa lambda light chain. Both immunoglobulin G and
immunoglobulin M antibodies against platelets were identified.
Alpha-fetoprotein and carcinoembryonic agent were in normal range.
Serum protein electrophoresis showed no evidence of monoclonal
gammopathy. Coombs and HIV tests were negative. Bone marrow
aspiration and biopsy demonstrated a hypocellular marrow (20%)
with marked reduction in trilineage hematopoiesis. There was lym3374
phocytosis, predominantly of T lymphocytes. A diagnosis of idiopathic thrombocytopenic purpura was made, and the patient was
placed on prednisone at 80 mg per day, and platelet count improved to
41,000 within 48 hours. After platelet count dropped again, the patient
was treated with rituximab at 375 mg/m2. At this time, he was transferred to the City of Hope National Medical Center (Duarte, CA),
where bone marrow aspiration and biopsy demonstrated severe hypocellular marrow (⬍ 5%) with marked reduction in hematopoiesis,
consistent with severe aplastic anemia (severe aplastic anemia [SAA];
Fig 2). No evidence of lymphoma or leukemia was found. The patient
was placed on cyclosporine. A thoracoscopic-assisted anterior mediastinotomy and biopsy of the mediastinal mass was consistent with a
thymoma. At this time, it was thought that due to the autoimmune
mediated pancytopenia the patient might have considerable difficulty
tolerating chemotherapy. We elected to perform a thymectomy in an
attempt to ablate the source of antibodies thereby improving the
chances of recovery from bone marrow aplasia.
On May 12, 2004, a right posterolateral thoracotomy was performed and the thymic mass resected en bloc along with part of the
pericardium. The thymic tumor weighed 731 g and measured 15.0 cm
in greatest dimension. The histology was consistent with a type A
thymoma (WHO classification). Postoperatively the patient was continued on cyclosporine, granulocyte colony-stimulating factor, and
platelet transfusions to maintain platelet count above 60,000/mm3.
One month after surgery, a repeat bone marrow aspiration and biopsy showed persistent SAA. The patient underwent allogenic sibling
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Diagnosis in Oncology
Fig 1.
peripheral stem-cell transplantation for treatment of AA. He tolerated the
from the hospital 1 month later. A repeat bone marrow examination 1
year later demonstrated a normocellular marrow with active trilineage
hematopoeisis. Thirty-two months after the completion of therapy, there
was no evidence of recurrent thymoma. He had excellent graft function
with mild graft-versus-host disease of the mucosa and liver. He has been
maintained on immunosuppressive therapy with cyclosporine and mycophenolate mofetil.
Myasthenia gravis is a common complication of thymoma
caused by immune damage to the motor end plate. Pure red cell
aplasia, often in combination with idiopathic thrombocytic purpura has been reported much less commonly in association with
thymomas, and aplastic anemia has been reported after thymectomy.1,2 To the best of our knowledge, there are no published reports
of patients with aplastic anemia resulting from thymoma who have
undergone successful bone marrow transplantation after resection
of the thymoma. The challenges of combining these treatments in
this case arose from difficulties in treating the aplastic anemia with
the thymoma in place versus the challenges of resecting the thymoma in the setting of severe pancytopenia. Cyclosporine has been
shown to produce a good response in patients with red cell aplasia.
While SAA can respond to cyclosporine alone, it is less effective
than cyclosporine plus antithymocyte globulin.3,4 Approximately
60% of patients with SAA respond to combination of antithymocyte globulin plus cyclosporine; however, the response may not be
durable. Allogeneic bone marrow transplantation remains the curative treatment for SAA.4 A recent report also showed that patients
with agenerative anemia who have undergone thymectomy have
not had a durable response.5 One of three such patients who
underwent the operation has had complete remission for 2 years.
Our patient did not respond to cyclosporine; however, thymectomy and allogeneic stem-cell transplantation resulted in normalization of his blood count and bone marrow function. Fifty percent
of all patients with red cell aplasia will have a thymoma. The
incidence of SAA is unknown. Twenty-five to 30% of those who
undergo thymectomy will be cured of the RCA. It has been suggested that any patient with red cell aplasia should have thymectomy through a median sternotomy.6 We approached the
thymoma via posterolateral thoracotomy to have a better visualization of the phrenic nerve and to improve hemostasis in the face
of severely suppressed platelet counts.
Vijay Trisal, Auayporn Nademanee, Sean K. Lau, and
Frederic W. Grannis Jr
From the Departments of Surgical Oncology, Hematology, Pathology, and
Thoracic Surgery, City of Hope National Medical Center, Duarte, CA
© 2007 by American Society of Clinical Oncology
The author(s) indicated no potential conflicts of interest.
1. Ritchie DS, Underhill C, Grigg AP: Aplastic anemia as a late complication of
thymoma in remission. Eur J Hematol 68:389-391, 2002
2. Kobayashi H, Kitano K, Furuta S, et al: Aplastic anemia and idiopathic
thrombocytopenic purpura with antibody to platelet glycoprotein IIb/IIIa following
Resection of malignant thymoma. Acta hematol 90:42-45, 1993
3. Liozon E, Touati M, Bordessoule D, et al: Thymoma associated pancytopenia: Effectiveness of cyclosporine A. Ann Hematol 77:175-178, 1998
4. Neal S, Young S, Scheinberg P, et al: Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108:2509-2519, 2006
5. Marks P, Marks C: Thymoma and aregenerative anemia. South Med J
81:1182-1184, 1988
6. Zeok JV, Todd EP, Utley JR, et al: The role of thymectomy in red cell aplasia.
Ann Thorac Surg 28:257-260
Fig 2.
DOI: 10.1200/JCO.2007.11.6871
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Copyright © 2007 American Society of Clinical Oncology. All rights reserved.