Case 2Case 2

Dr. Sathima Natarajan M.D.Dr. Sathima Natarajan M.D.Kaiser Permanente Medical CenterKaiser Permanente Medical Center

SunsetSunset

HistoryHistory24 year old male presented with a 3 day 24 year old male presented with a 3 day history of right flank pain, sharp in naturehistory of right flank pain, sharp in natureDenies fever, chills, hematuria or dysuria.Denies fever, chills, hematuria or dysuria.Past history: left side kidney stone Past history: left side kidney stone PE: enlarged left supraclavicular lymph PE: enlarged left supraclavicular lymph nodenode

CT SCANCT SCAN

Multiple masses in the pelvis measuring Multiple masses in the pelvis measuring up to 10 cm in maximum dimension, along up to 10 cm in maximum dimension, along the aorta and inferior vena cavathe aorta and inferior vena cavaDifferential diagnosis: lymphoma vs. Differential diagnosis: lymphoma vs. testicular neoplasmtesticular neoplasmA 3.5 cm left supraclavicular lymph node A 3.5 cm left supraclavicular lymph node was was biopsiedbiopsied and submitted to rule out and submitted to rule out lymphomalymphoma

TOUCH PREP

TOUCH PREP

LEFT SUPRACLAVICULAR LYMPH NODE

Cytokeratin

VIMENTIN

EMA (+)

DESMIN

CD 99 (+)

WT1 – RARE POSITIVE CELLS

Summary of immunologic findingsSummary of immunologic findings

Positive: Pankeratin, EMA, Vimentin, Positive: Pankeratin, EMA, Vimentin, Focally positive: desmin, WT1, CD99, MSAFocally positive: desmin, WT1, CD99, MSANegative: LCA, Tdt, chromogranin, Negative: LCA, Tdt, chromogranin,

synaptophysin, S100, TTFsynaptophysin, S100, TTF--1, CK7 and 1, CK7 and CK20CK20

Differential diagnosisDifferential diagnosisEwing’s sarcoma/primitive neuroectodermal Ewing’s sarcoma/primitive neuroectodermal tumor grouptumor groupEmbryonal rhabdomyosarcomaEmbryonal rhabdomyosarcomaAlveolar rhabdomyosarcomaAlveolar rhabdomyosarcomaNeuroblastomaNeuroblastomaMalignant lymphomaMalignant lymphomaSite specific neoplasms: Merkel cell carcinoma Site specific neoplasms: Merkel cell carcinoma for scalp, small cell undifferentiated ca & solid for scalp, small cell undifferentiated ca & solid variant of adenoid cystic ca for head and neck variant of adenoid cystic ca for head and neck region (parotid)region (parotid)

Molecular findingsMolecular findings

Molecular cytogenetic analysis of the Molecular cytogenetic analysis of the paraffin block using fluorescent in situ paraffin block using fluorescent in situ hybridization (F.I.S.H) is positive for 22q12 hybridization (F.I.S.H) is positive for 22q12 translocationtranslocation-- highly characteristic marker highly characteristic marker for Ewing’s sarcoma or desmoplastic small for Ewing’s sarcoma or desmoplastic small round cell tumorround cell tumor

Desmoplastic small round cell tumorDesmoplastic small round cell tumor

Highly aggressive neoplasm described by Highly aggressive neoplasm described by Gerald and Rosai (1991)Gerald and Rosai (1991)

Intraabdominal desmoplastic small round cell tumor. Report of 19Intraabdominal desmoplastic small round cell tumor. Report of 19 cases of a distinctive cases of a distinctive type of high grade polyphenotypic malignancy affecting young indtype of high grade polyphenotypic malignancy affecting young individuals. Am J Surg ividuals. Am J Surg Pathol 1991;15:499Pathol 1991;15:499--5151

Predilection for young males (15Predilection for young males (15--41 yrs)41 yrs)Male to female ratio: 4:1Male to female ratio: 4:1Case reports of this tumor in very young Case reports of this tumor in very young children, in elderly male and in females have children, in elderly male and in females have been reportedbeen reportedThe expanding clinical spectrum of desmoplastic small round cellThe expanding clinical spectrum of desmoplastic small round cell tumor: a tumor: a report of two cases with molecular confirmation. Hum Pathol. 199report of two cases with molecular confirmation. Hum Pathol. 1999; 30:4309; 30:430--435435

Clinical presentationClinical presentationMost common clinical presenting Most common clinical presenting symptoms and signs: Peritoneal cavitysymptoms and signs: Peritoneal cavity

abdominal painabdominal painabdominal distensionabdominal distensionpalpable abdominal masspalpable abdominal mass

•• Other primary sites: paratesticular regionOther primary sites: paratesticular regionpleura, posterior cranial fossa, soft tissue pleura, posterior cranial fossa, soft tissue and bone, ovary and parotid glandand bone, ovary and parotid gland

Desmoplastic small round cell tumorDesmoplastic small round cell tumorArise from an undifferentiated cell with potential for Arise from an undifferentiated cell with potential for multiple lines of differentiationmultiple lines of differentiationGerald et alGerald et al. suggested that DSRCT can be a primitive . suggested that DSRCT can be a primitive tumor histologically related to mesothelium tumor histologically related to mesothelium ((mesothelioblastomamesothelioblastoma) )

1.1. prevalence of its main prevalence of its main locationlocation (peritoneal (peritoneal and pleural surfaces)and pleural surfaces)

2.2. repeated demonstration of repeated demonstration of chromosomalchromosomaltranslocation involving translocation involving WT1WT1 gene, also gene, also expressed in primitive mesotheliumexpressed in primitive mesothelium

Subsequent paper described tumor involving parotid Subsequent paper described tumor involving parotid glands, brain, scalp and ethmoid sinusesglands, brain, scalp and ethmoid sinuses

Desmoplastic small round cell tumorDesmoplastic small round cell tumorNeoplastic masses are solid, firm, multilobulated with gray Neoplastic masses are solid, firm, multilobulated with gray tan cut surfaces tan cut surfaces Tumors consists of solid sheets, large nests, small Tumors consists of solid sheets, large nests, small clusters and cords of cohesive small, round, cells lying in clusters and cords of cohesive small, round, cells lying in a hypocellular, desmoplastic, collagenous stromaa hypocellular, desmoplastic, collagenous stromaTumor cells small with hyperchromatic nuclei, clumped Tumor cells small with hyperchromatic nuclei, clumped chromatin, inconspicuous nucleoli and ill defined light chromatin, inconspicuous nucleoli and ill defined light eosinophilic cytoplasmeosinophilic cytoplasmMitotic figures are numerousMitotic figures are numerousNecrosis, dystrophic calcification and rosette like Necrosis, dystrophic calcification and rosette like structures may be seenstructures may be seen

Desmoplastic small round cell tumorDesmoplastic small round cell tumorSpecific immunohistochemical staining profile trilineage Specific immunohistochemical staining profile trilineage coexpression(epithelial, muscular and neural markers)coexpression(epithelial, muscular and neural markers)

Immunohistochemical staining profile:Immunohistochemical staining profile:Cytokeratin 88%Cytokeratin 88%CAM 5.2 87% CAM 5.2 87% Desmin 81% (dot like)Desmin 81% (dot like)Vimentin 88%Vimentin 88%NSE 84%NSE 84%CD99 23%CD99 23%Actin 3%Actin 3%WT1 91%WT1 91%

Desmoplastic small round cell tumor. A clinicopathologic,Desmoplastic small round cell tumor. A clinicopathologic,Immunohistochemical, and molecular study of 32 tumors.Immunohistochemical, and molecular study of 32 tumors.Lae et al. Am J Surg Pathol 26 (7): 823Lae et al. Am J Surg Pathol 26 (7): 823--835, 2002835, 2002

Desmoplastic small round cell tumorDesmoplastic small round cell tumor

Reciprocal translocation Reciprocal translocation t (11;22)(p13;q11 or q12)t (11;22)(p13;q11 or q12)

Fusion of exon 7 of the Ewings sarcoma Fusion of exon 7 of the Ewings sarcoma gene EWS on chromosome 22 with exon 8 gene EWS on chromosome 22 with exon 8 of the Wilm’s tumor suppressor gene WT1 of the Wilm’s tumor suppressor gene WT1 on chromosome 11on chromosome 11The chimeric transcript corresponding to The chimeric transcript corresponding to the fusion gene product can be detected the fusion gene product can be detected by reverse transcriptaseby reverse transcriptase--PCRPCR

Treatment and prognosisTreatment and prognosis

Chemotherapy: cyclophosphamide, Chemotherapy: cyclophosphamide, doxorubicin, vincristine, ifosfamide and doxorubicin, vincristine, ifosfamide and etoposideetoposideRecommendation: adjuvant Recommendation: adjuvant abdominopelvic radiotherapy followed by abdominopelvic radiotherapy followed by surgery and chemotherapysurgery and chemotherapyDSRCT: highly aggressive clinical course DSRCT: highly aggressive clinical course with multiple local recurrences with multiple local recurrences The average survival is <2 to 3 yearsThe average survival is <2 to 3 years

Desmoplastic small round cell tumorDesmoplastic small round cell tumor

It is important to consider DSRCT as a possible It is important to consider DSRCT as a possible diagnosis when a young male presents with non diagnosis when a young male presents with non specific abdominal symptoms and radiologic specific abdominal symptoms and radiologic evidence of a disseminated, intraabdominal evidence of a disseminated, intraabdominal malignancymalignancySmall round cells in a fibrous stromaSmall round cells in a fibrous stromaTrilineage immunohistochemical expressionTrilineage immunohistochemical expressionEWS/WT1 chimeric transcript: t(11;22)(p13;q12)EWS/WT1 chimeric transcript: t(11;22)(p13;q12)

Desmoplastic small round cell tumorDesmoplastic small round cell tumor-- ReferencesReferences

Gerald WL, Rosai J. Case 2 desmoplastic small cell tumor with Gerald WL, Rosai J. Case 2 desmoplastic small cell tumor with divergent differentiation. Pediatr Pathol 1989; 9:177divergent differentiation. Pediatr Pathol 1989; 9:177--183.183.Gerald WL et al. Intraabdominal desmoplastic small round cell Gerald WL et al. Intraabdominal desmoplastic small round cell tumor: report of 19 cases of a distinctive type of hightumor: report of 19 cases of a distinctive type of high--grade grade polyphenotypic malignancy affecting young individuals. Am J Surgpolyphenotypic malignancy affecting young individuals. Am J SurgPathol 1991; 12:449Pathol 1991; 12:449--513.513.Ordonez NG. Desmoplastic small round cell tumor. A Ordonez NG. Desmoplastic small round cell tumor. A histopathologic study of 39 cases with emphasis on unusual histopathologic study of 39 cases with emphasis on unusual histologic patterns. An ultrastructural and immunohistochemical histologic patterns. An ultrastructural and immunohistochemical study with emphasis on new immunohistochemical markers. Am J study with emphasis on new immunohistochemical markers. Am J Surg Pathol 1998; 22: 1303Surg Pathol 1998; 22: 1303--13; 131413; 1314--2727Sawyer et al. A novel reciprocal chromosome translocation Sawyer et al. A novel reciprocal chromosome translocation t(11;22)(p13;q12) in an intraabdominal desmoplastic small round t(11;22)(p13;q12) in an intraabdominal desmoplastic small round cell tumor. Am J Surg Pathol 1992; 16:411cell tumor. Am J Surg Pathol 1992; 16:411--66Wolf AN et al. The expanding clinical spectrum of desmoplastic Wolf AN et al. The expanding clinical spectrum of desmoplastic small round cell tumor: a report of two cases with molecular small round cell tumor: a report of two cases with molecular confirmation. Hum Pathol 1999; 30:430confirmation. Hum Pathol 1999; 30:430--55Hassan et al. Intraabdominal desmoplastic small round cell tumorHassan et al. Intraabdominal desmoplastic small round cell tumors. s. A diagnostic and therapeutic challenge. Cancer 2005; Vol A diagnostic and therapeutic challenge. Cancer 2005; Vol (104)6:1264(104)6:1264--7070