Case 2. Dr. Sathima Natarajan M.D. Kaiser Permanente Medical Center Sunset
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1 Case 2 Dr. Sathima Natarajan M.D. Kaiser Permanente Medical Center Sunset
2 History 24 year old male presented with a 3 day history of right flank pain, sharp in nature Denies fever, chills, hematuria or dysuria. Past history: left side kidney stone PE: enlarged left supraclavicular lymph node
3 CT SCAN Multiple masses in the pelvis measuring up to 10 cm in maximum dimension, along the aorta and inferior vena cava Differential diagnosis: lymphoma vs. testicular neoplasm A 3.5 cm left supraclavicular lymph node was biopsied and submitted to rule out lymphoma
4 TOUCH PREP
5 TOUCH PREP
6 LEFT SUPRACLAVICULAR LYMPH NODE
7
8
9
10
11 Cytokeratin
12 VIMENTIN
13 EMA (+)
14 DESMIN
15 CD 99 (+)
16 WT1 RARE POSITIVE CELLS
17 Summary of immunologic findings Positive: Pankeratin, EMA, Vimentin, Focally positive: desmin, WT1, CD99, MSA Negative: LCA, Tdt, chromogranin, synaptophysin, S100, TTF-1, CK7 and CK20
18 Differential diagnosis Ewing s sarcoma/primitive neuroectodermal tumor group Embryonal rhabdomyosarcoma Alveolar rhabdomyosarcoma Neuroblastoma Malignant lymphoma Site specific neoplasms: Merkel cell carcinoma for scalp, small cell undifferentiated ca & solid variant of adenoid cystic ca for head and neck region (parotid)
19 Molecular findings Molecular cytogenetic analysis of the paraffin block using fluorescent in situ hybridization (F.I.S.H) is positive for 22q12 translocation- highly characteristic marker for Ewing s sarcoma or desmoplastic small round cell tumor
20 Desmoplastic small round cell tumor Highly aggressive neoplasm described by Gerald and Rosai (1991) Intraabdominal desmoplastic small round cell tumor. Report of 19 cases of a distinctive type of high grade polyphenotypic malignancy affecting young individuals. ividuals. Am J Surg Pathol 1991;15: Predilection for young males (15-41 yrs) Male to female ratio: 4:1 Case reports of this tumor in very young children, in elderly male and in females have been reported The expanding clinical spectrum of desmoplastic small round cell tumor: a report of two cases with molecular confirmation. Hum Pathol. 1999; 9; 30:
21 Clinical presentation Most common clinical presenting symptoms and signs: Peritoneal cavity abdominal pain abdominal distension palpable abdominal mass Other primary sites: paratesticular region pleura, posterior cranial fossa, soft tissue and bone, ovary and parotid gland
22 Desmoplastic small round cell tumor Arise from an undifferentiated cell with potential for multiple lines of differentiation Gerald et al.. suggested that DSRCT can be a primitive tumor histologically related to mesothelium (mesothelioblastoma) 1. prevalence of its main location (peritoneal and pleural surfaces) 2. repeated demonstration of chromosomal translocation involving WT1 gene, also expressed in primitive mesothelium Subsequent paper described tumor involving parotid glands, brain, scalp and ethmoid sinuses
23 Desmoplastic small round cell tumor Neoplastic masses are solid, firm, multilobulated with gray tan cut surfaces Tumors consists of solid sheets, large nests, small clusters and cords of cohesive small, round, cells lying in a hypocellular, desmoplastic, collagenous stroma Tumor cells small with hyperchromatic nuclei, clumped chromatin, inconspicuous nucleoli and ill defined light eosinophilic cytoplasm Mitotic figures are numerous Necrosis, dystrophic calcification and rosette like structures may be seen
24 Desmoplastic small round cell tumor Specific immunohistochemical staining profile trilineage coexpression(epithelial, muscular and neural markers) Immunohistochemical staining profile: Cytokeratin 88% CAM % Desmin 81% (dot like) Vimentin 88% NSE 84% CD99 23% Actin 3% WT1 91% Desmoplastic small round cell tumor. A clinicopathologic, Immunohistochemical, and molecular study of 32 tumors. Lae et al. Am J Surg Pathol 26 (7): , 835, 2002
25 Desmoplastic small round cell tumor Reciprocal translocation t (11;22)(p13;q11 or q12) Fusion of exon 7 of the Ewings sarcoma gene EWS on chromosome 22 with exon 8 of the Wilm s tumor suppressor gene WT1 on chromosome 11 The chimeric transcript corresponding to the fusion gene product can be detected by reverse transcriptase-pcr
26 Treatment and prognosis Chemotherapy: cyclophosphamide, doxorubicin, vincristine, ifosfamide and etoposide Recommendation: adjuvant abdominopelvic radiotherapy followed by surgery and chemotherapy DSRCT: highly aggressive clinical course with multiple local recurrences The average survival is <2 to 3 years
27 Desmoplastic small round cell tumor It is important to consider DSRCT as a possible diagnosis when a young male presents with non specific abdominal symptoms and radiologic evidence of a disseminated, intraabdominal malignancy Small round cells in a fibrous stroma Trilineage immunohistochemical expression EWS/WT1 chimeric transcript: t(11;22)(p13;q12)
28 Desmoplastic small round cell tumor- References Gerald WL, Rosai J. Case 2 desmoplastic small cell tumor with divergent differentiation. Pediatr Pathol 1989; 9: Gerald WL et al. Intraabdominal desmoplastic small round cell tumor: report of 19 cases of a distinctive type of high-grade grade polyphenotypic malignancy affecting young individuals. Am J Surg Pathol 1991; 12: Ordonez NG. Desmoplastic small round cell tumor. A histopathologic study of 39 cases with emphasis on unusual histologic patterns. An ultrastructural and immunohistochemical study with emphasis on new immunohistochemical markers. Am J Surg Pathol 1998; 22: ; 13; Sawyer et al. A novel reciprocal chromosome translocation t(11;22)(p13;q12) in an intraabdominal desmoplastic small round cell tumor. Am J Surg Pathol 1992; 16:411-6 Wolf AN et al. The expanding clinical spectrum of desmoplastic small round cell tumor: a report of two cases with molecular confirmation. Hum Pathol 1999; 30:430-5 Hassan et al. Intraabdominal desmoplastic small round cell tumors. A diagnostic and therapeutic challenge. Cancer 2005; Vol (104)6:
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