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Journal of Clinical Oncology, Vol 25, No 22 (August 1), 2007: pp. 3372-3374 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.11.9487
Desmoplastic Small Round Cell Tumor of Meckels DiverticulumPediatric Surgical Oncology Services, Tata Memorial Centre, Bombay, India
Department of Pathology, Tata Memorial Centre, Bombay, India
Department of Pediatric Oncology, Tata Memorial Centre, Bombay, India
Department of Radiation Oncology, Tata Memorial Centre, Bombay, India
Department of Radiodiagnosis, Tata Memorial Centre, Bombay, India
Department of Radiation Oncology, Tata Memorial Centre, Bombay, India
Department of Pediatric Oncology, Tata Memorial Centre, Bombay, India
Department of Pathology, Tata Memorial Centre, Bombay, India
Department of Pediatric Oncology, Tata Memorial Centre, Bombay, India A 6-year-old boy presented with 6-month history of intermittent abdominal pain associated with episodic vomiting suggestive of subacute intestinal obstruction, which had worsened significantly over the preceding week. Upon physical examination, a 6 x 5 cm mass was palpable in the right iliac fossa extending into the pelvis. A computed tomography (CT) scan revealed a 5.2 x 9.5 x 6.5 cm heterogeneously enhancing mass with ill-defined margins, occupying the right iliac fossa. The mass caused extrinsic compression of ileal loop and abutted the anterior abdominal wall and the iliopsoas muscle with indistinct fat planes between them. There was dilation of small bowel loops and mild ascites (Fig 1). Core biopsy revealed a malignant round cell tumor with rosette-like structures. The tumor cells had an equivocal reaction to desmin and mic2. The clinicopathological features favored a primitive neuroectodermal tumor. Metastatic work-up including bone marrow studies, bone scan, and CT scan of thorax was negative. Combination chemotherapy was initiated as per the institutional protocol for primitive neuroectodermal tumor comprising of a six-drug regimen of vincristine, doxorubicin, cyclophosphamide, dactinomycin, ifosphamide, and etoposide. After the initial 9 weeks of induction therapy, the patient underwent re-evaluation of his disease status. CT scan showed a persistent mass of 5.0 x 8.0 x 6.0 cm with multiple areas of necrosis. There was no change in the extent of the mass, but it appeared well-defined. The proximal small bowel loops were still dilated. Positron emission tomography scan showed central photo deficient area suggestive of necrosis with abnormal tracer uptake at the periphery of the lesion. On exploratory laparotomy, the mass was seen arising from the Meckels diverticulum (Fig 2). No other focus of disease was noted in the abdominal cavity. Resection of ileal loop along with the Meckels diverticulum was performed and bowel continuity restored by an end-to-end anastomosis. Grossly the mass measured 7.5 cm in diameter and the cut surface, largely consisted of areas of necrosis and hemorrhage with some firm, white areas. Microscopically, the tumor was composed of small round malignant cells arranged in pseudo rosettes and also in small groups and sheets (Fig 3A). Tumor cells were located predominantly in the subserosal plane and also invaded the muscularis propria and mucosa of the intestine. Presence of loose fibrous stroma was seen focally. Immunohistochemistry demonstrated a polyphenotypic differentiation in the form of desmin (Fig 3B) and cytokeratin positivity (Fig 3C). mic2, synaptophysin, chromogranin, S-100, WT-1, neuron specific enolase, and epithelial membrane antigen were negative. Considering the above phenotype and immunoprofile, this serosal-based tumor involving the Meckels diverticulum was diagnosed as desmoplastic small round cell tumor (DSRCT). Reverse transcriptase polymerase chain reaction revealed the EWS-WT1 gene fusion chimeric transcript, confirming the above diagnosis (Fig 3D).
In view of the entire peritoneal cavity being at risk of harboring occult microscopic disease, due to the known natural history of DSRCT, the patient was treated with whole abdominopelvic radiotherapy with parallel opposed anteroposterior portals with 6 MV photons on a linear accelerator with customized shielding for the kidneys from day 1 to a dose of 30.6 Gy in 17 fractions followed by a conformal boost of 14.4 Gy in 8 fractions to the tumor bed for a total tumor bed dose of 45 Gy in 25 fractions over 5 weeks. Concurrent chemotherapy was administered with radiation after which maintenance chemotherapy was initiated. The patient developed anthracycline-induced cardiotoxicity after a cumulative doxorubicin dose of 300 mg/m2 subsequent to which the drug was stopped and replaced with dactinomycin. The patient is now receiving regular follow-up and remains disease free at the time of this report. DSRCT is a rare and highly aggressive neoplasm described as a separate entity in 1989.1 The exclusivity of DSRCT is due to its distinct clinical, histologic and immunophenotypic features that make it an often misdiagnosed neoplasm of children and young adult.2 It has a propensity for serosal surfaces, especially in the peritoneal cavity, however, it has also been described at extra-abdominal locations.3 The abdominal disease is characterized by the presence of large abdominal masses without any obvious organ base and widespread peritoneal involvement. However, this case is unique wherein the abdominal disease was localized in the Meckels diverticulum without involvement of the remaining peritoneal surface. The tumor location compressing the small bowel and causing obstruction probably led to early detection of the lesion, which could perhaps explain the absence of generalized peritoneal disease. A systematic review of indexed medical literature did not reveal any previously published reports of DSRCT arising in the Meckels diverticulum. The histogenesis of DSRCT is uncertain. However, because of its close association with mesothelial-lined surfaces, a mesothelial origin has been suggested (mesothelioblastoma).2 Histologically, it is typically composed of nests of small, undifferentiated round or oval hyperchromatic cells embedded in abundant desmoplastic stroma. DSRCT has a polyphenotypic immunostaining profile with reactivity for epithelial (keratin, epithelial membrane antigen), neural (neuron-specific enolase), mesenchymal (vimentin), and muscle markers (desmin).4 The chromosomal abnormality, t (11; 22) (p13; q12), involving the EWS gene on 22q12 and the WT1 gene on 11p13 is very specific for DSRCT.5 This gene fusion is postulated to produce an oncogenic chimeric protein that induces production of endogenous platelet-derived growth factor,6 T-cell acute lymphoblastic leukemia-associated antigen 1 protein,7 and interleukin-2/15 receptor.8 Each of these is important in tumorigenesis. Multidisciplinary treatment including intensive multiagent chemotherapy, aggressive debulking surgery (> 90% resection), 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. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES 1. Gerald WL, Rosai J: Case 2: desmoplastic small round cell tumor with divergent differentiation. Pediatr Pathol 9:177-183, 1989[Medline] 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, 1991[Medline] 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[Medline] 4. Chang F: Desmoplastic small round cell tumors: Cytologic, histologic, and immunohistochemical features. Arch Pathol Lab Med 130:728-732, 2006[Medline] 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[CrossRef][Medline] 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, 1997[CrossRef][Medline] 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 sarcoma-Wilms' 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, 2002[CrossRef][Medline] 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[CrossRef][Medline]
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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