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Background
The desmoplastic small round blue cell tumor is a recently delineated tumor which occurs in children and young adults with a male preference. It presents as a large mass within the abdomen, usually the pelvic region, and may be accompanied with extensive tumor implants throughout the peritoneum.
These tumors have been reported in a number of extraperitoneal organs and sites. It is an aggressive tumor with a poor prognosis. The pathologist must distinguish this tumor from other small round blue cell tumors of childhood.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION AGE RANGE-MEDIAN Older children to young adults Males predominance
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL Large bulky tumor CENTRAL NERVOUS SYSTEM KIDNEY Desmoplastic Small Round Cell Tumor of the Kidney.
Su MC, Jeng YM, Chu YC.
Departments of *Pathology, double daggerUrology, Min-Sheng General Hospital; and the daggerDepartment of Pathology, National Taiwan University Hospital, and College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Am J Surg Pathol. 2004 Oct;28(10):1379-1383. Abstract quote
Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive, malignant tumor usually present with widespread abdominal serosal involvement. Isolated cases occur in limbs, head and neck, and brain.
We present a case of primary DSRCT of the kidney in a 41-year-old man. The tumor showed morphologic, immunohistochemical, and molecular characteristics similar to DSRCTs arising in other sites. Epithelial and mesenchymal markers were coexpressed in the tumor cells. RT-PCR analysis showed EWS-WT1 fusion transcripts resulting from the t(11;22)(p13;q12) reciprocal translocation. DSRCT should be considered in the differential diagnosis of small blue round cell tumors of the kidney.LUNG
Desmoplastic small round cell tumor of the lung.Syed S, Haque AK, Hawkins HK, Sorensen PH, Cowan DF.
Department of Pathology, University of Texas Medical Branch, Galveston 77555, USA.
Arch Pathol Lab Med 2002 Oct;126(10):1226-8 Abstract quote An extra-abdominal desmoplastic small round cell tumor (DSRCT) of the lung with immunohistochemical, ultrastructural, and cytogenetic evidence of multidirectional differentiation is reported.
We demonstrate that DSRCTs of the lung and pleura show morphologic, molecular, genetic, and ultrastructural features similar to DSRCTs arising in other sites. The tumor showed coexpression of cytokeratins (AE1/3, epithelial membrane antigen, CAM 5.2) and mesenchymal markers (vimentin, desmin, neuron-specific enolase), as well as WT1.
Ultrastructurally, intracytoplasmic whorls of intermediate filaments, similar to previous descriptions of DSRCT in nonthoracic sites, were also demonstrated in this case. EWS-WT1 gene fusion characteristic of DSRCT with the t(11;22)(q13;q12) translocation was demonstrated in this tumor.
PANCREAS Desmoplastic small cell tumor in the pancreas.
Bismar TA, Basturk O, Gerald WL, Schwarz K, Adsay NV.
Department of Pathology, Harper University Hospital, Wayne State University, Detroit, MI 48201, USA.
Am J Surg Pathol. 2004 Jun;28(6):808-12. Abstract quote
Desmoplastic small cell tumor (DSCT) is a distinct type of small blue cell tumors and is characterized by the unique karyotypic aberration involving the fusion of the Ewing's sarcoma (EWS) gene and Wilms' tumor (WT1) gene. Typically, it grows along serosal surfaces; however, in some cases, the tumor presents as a dominant mass in an internal organ. Examples of DSCT forming a primary mass in ovary, testes, and brain have been described, but its presentation as a primary pancreatic mass has not been reported previously.
The case reported here is a 31-year-old woman who presented with a 14-cm mass in the pancreas. There were smaller nodules on the peritoneal surfaces that were regarded clinically as metastasis from a primary pancreatic tumor. During the frozen section, the diagnosis of a poorly differentiated endocrine carcinoma of pancreatic origin was rendered and patient underwent subtotal pancreatectomy.
On microscopic examination, the tumor was composed of large nests and broad bands of small blue cells, separated by fibrous stroma. Immunohistochemical stains showed positivity of the tumor cells for cytokeratins (AE1:AE3 and CAM5.2), neuron specific enolase, desmin and WT1, whereas chromogranin, S-100, and CD99 were negative. Since this immunoprofile is characteristic of DSCT, molecular analysis was performed which revealed the presence of EWS-WT1 gene fusion characteristic of DSCT.
This case shows that in addition to primary pancreatic tumors characterized by prominent cellularity such as solid pseudopapillary tumors, acinar cell carcinoma, pancreatoblastoma, endocrine tumors, and other small blue cell tumors, the differential diagnosis of cellular, stroma-poor neoplasia in the pancreas also includes DSCT.
This case is also another demonstrative example of how DSCT may form a dominant mass in intraabdominal organs.PLEURA SCROTUM SINONASAL
Sinonasal desmoplastic small round cell tumor: a case report.Finke NM, Lae ME, Lloyd RV, Gehani SK, Nascimento AG.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA
Am J Surg Pathol 2002 Jun;26(6):799-803 Abstract quote A case of sinonasal desmoplastic small round cell tumor in a 21-year-old woman is presented. The tumor possessed the diagnostic histologic, immunohistochemical, and genetic characteristics of desmoplastic small round cell tumor.
Histologically, the tumor was composed of nests of tumor cells surrounded by a desmoplastic stroma. Immunohistochemical staining was positive for keratin, vimentin, desmin, and, focally, neuron-specific enolase. The desmin immunopositivity was of a classic dot-like perinuclear pattern. RT-PCR analysis showed the fusion transcript resulting from the t(11;22)(p13;q12) reciprocal translocation.
This case of sinonasal desmoplastic small round cell tumor, the third reported case not associated with a serosal surface, further obscures the nature and histogenesis of this entity.
THORAX
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Distinctive appearance of solid nests of round to oval cells with a cellular desmoplastic stroma. There may be large areas of necrosis, cystic degeneration, and glandular arrangements CYTOLOGY
Cytology of desmoplastic small round cell tumor.Crapanzano JP, Cardillo M, Lin O, Zakowski MF.
Cytology Service, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer 2002 Feb 25;96(1):21-31 Abstract quote BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a high-grade malignant tumor that has a predilection for adolescent males and usually affects the abdominal cavity. The cytology literature regarding DSRCT, including aspirates and ascitic fluid, is limited. To the authors' knowledge, findings in ThinPrep slides have not been described previously.
METHODS: Seven cytologic specimens from five patients with histologically confirmed DSRCT were reviewed. Five specimens were fine-needle aspiration biopsies (FNABs), (liver, flank soft tissue, abdomen, and two resected colons [pericolic]) and two specimens were ascitic fluid. Cytologic features were studied in ThinPrep slides and direct smears, which included hematoxylin and eosin, Papanicolaou, and Quik-Dip stains.
RESULTS: All specimens showed moderate to high cellularity. The tumor cells were arranged singly and in clusters. The cells demonstrated high nuclear/cytoplasmic ratios, granular chromatin reminiscent of small cell carcinoma, usually inconspicuous nucleoli, smooth to irregular nuclear membranes, and frequent nuclear molding. The cytoplasm was scant to moderate, pale blue, and occasionally vacuolated. Pseudorosettes were observed in six specimens. One ThinPrep slide and the direct smears contained cells with perinuclear, cytoplasmic densities. Stromal fragments were present in the direct smears but were uncommon in ThinPrep. Three specimens were diagnosed as being consistent with DSRCT. Two specimens were diagnosed as malignant small cell tumor. Molecular studies performed on histologic material in four cases confirmed the presence of the diagnostic translocation, t(11;22)(p13;q12).
CONCLUSIONS: DSRCT may be diagnosed accurately in cytology specimens. Characteristic cytologic features include granular chromatin, smooth to irregular nuclear membranes, nuclear molding, cytoplasmic vacuoles, pseudorosettes, and metachromatic stroma. Cytoplasmic densities may be observed in direct smears and ThinPrep slides.
VARIANTS Adenoid cystic-like Carcinoid-like differentiation Minimal desmoplasia OSETOID Abdominal small round cell tumor with osteoid and EWS/FLI1.
Oshima Y, Kawaguchi S, Nagoya S, Wada T, Kokai Y, Ikeda T, Nogami S, Oya T, Hirayama Y.
Hum Pathol. 2004 Jun;35(6):773-5. Abstract quote
In this report, we described a case of multiple intraperitoneal tumors. Histologically, the tumors were composed of small round cells with malignant phenotype, necrotic areas, and islands of osteoid matrix in the stroma. In immunohistochemical and molecular analyses, the tumors expressed CD99 and EWS-Fli1 fusion gene. Production of osteoid by small round tumor cells was consistent with the histologic criteria of small-cell osteosarcoma, whereas expression of EWS-Fli1 was a characteristic genetic feature of Ewing's sarcoma family of tumor. Such tumors have been limited to a case in which histologically proven small-cell osteosarcoma of the scapula showed a chromosomal translocation, t(11;22)(q24;q12).Pseudorosette formations Rhabdoid cells Signet ring cells SPINDLE CELLS
- Alaggio R,
- Rosolen A,
- Sartori F,
- Leszl A,
- D'amore ES,
- Bisogno G,
- Carli M,
- Cecchetto G,
- Coffin CM,
- Ninfo V.
*Dipartimento di Scienze Oncologiche e Chirurgiche Universita di Padova and IOV (Istituto Oncologico Veneto) daggerClinica di Oncoematologia Pediatrica, Azienda Ospedaliera-Universita di Padova, Padova double daggerAnatomia patologica, Ospedale S. Bortolo, Vicenza, Italy section signDepartment of Pathology, Primary Children's Medical Center and University of Utah School of Medicine, Salt Lake City, UT
We report 2 intra-abdominal tumors originally diagnosed as leiomyosarcomas, occurring in adolescents, one as a second malignancy after a Hodgkin lymphoma. Both tumors exhibited unusual morphologic features characterized by spindle cells arranged in sheets or in fascicles, devoid of the typical desmoplastic stroma.
Cytokeratins and mesenchymal markers, including smooth muscle actin, desmin, and muscle specific actin, were coexpressed in the tumor cells, whereas EMA was negative. Reverse transcription-polymerase chain reaction analysis showed an EWS-WT1 fusion transcript. Both patients are alive and in complete remission at 3 and 13 years after diagnosis, respectively.
These tumors raise a variety of diagnostic possibilities. They could represent intra-abdominal desmoplastic small round cell tumor, with histologic features of epithelioid leiomyosarcoma or an unusual subtype of leiomyosarcoma with an EWS-WT1 transcript. Alternatively, they could represent an unrecognized subgroup of tumors with spindle cell morphology, bearing the same translocation as desmoplastic small round cell tumor, but characterized by a more favorable clinical course.
SPECIAL STAINS/
IMMUNOPEROXIDASECHARACTERIZATION EWS-WT1 FUSION GENE PRODUCT
Immunophenotype of Desmoplastic Small Round Cell Tumors as Detected in Cases with EWS-WT1 Gene Fusion Product.Zhang PJ, Goldblum JR, Pawel BR, Fisher C, Pasha TL, Barr FG.
University of Pennsylvania Medical Center (PJZ, TLP, FGB), Philadelphia, Pennsylvania.
Mod Pathol 2003 Mar;16(3):229-35 Abstract quote Desmoplastic small round cell tumor is a rare tumor typically involving peritoneum. Although the histogenesis of desmoplastic small round cell tumor has yet to be elucidated, immunophenotypical and morphological analysis shows a characteristic divergent phenotype overlapping with other round cell tumors such as Ewing's sarcoma/primitive neuroectodermal tumor, rhabdomyosarcoma, small cell mesothelioma, and carcinoma.
Detection of the EWS-WT1 gene fusion is characteristic of desmoplastic small round cell tumor and has been used reliably in tumor diagnosis. In this study, we evaluated the immunophenotype of 23 desmoplastic small round cell tumor cases with the EWS-WT1 gene fusion product identified by reverse transcription-polymerase chain reaction. Paraffin sections were stained with antibodies against calretinin, WT1 (C19), desmin, myoglobin, MyoD, Myf5, myogenin, placental alkaline phosphatase, cytokeratins, MIC2, HER2/neu and c-kit using standard immunohistochemical methods. Immunoreactivity was evaluated semiquantitively by light microscopy. Desmoplastic small round cell tumors showed reactivity with calretinin in 4/21, desmin in 21/23, myoglobin in 5/17, placental alkaline phosphatase in 17/21, HER2/neu in 7/18 (3+ in 1 and 1+ in 6), c-kit in 2/14, MIC2 in 13/23, WT1 in 16/23, CAM5.2 in 21/23, and AE1/3 in 16/23 cases.
The most sensitive myogenic and epithelial markers are desmin and CAM 5.2. Although nuclear reactivity of the early myogenic regulatory factors (MyoD, myogenin, Myf5) was not detected, myoglobin immunoreactivity was present in 29% of desmoplastic small round cell tumors. HER2/neu overexpression (3+) and c-kit expression are uncommon in desmoplastic small round cell tumors.
A panel of myogenic and epithelial markers should be used to detect the divergent phenotype in desmoplastic small round cell tumors, a key feature in the differential diagnosis. Detection of EWS-WT1 fusion becomes critical for the diagnosis when the characteristic divergent phenotype cannot be detected immunohistochemically.
A Comparative Study With Other Small Round Cell TumorsRaphaëlle Barnoud, M.D.; Jean-Christophe Sabourin, M.D., Ph.D.; Dominique Pasquier, M.D.; Dominique Ranchère, M.D.; Christiane Bailly, M.D.; Marie-Josée Terrier-Lacombe, M.D.; Basile Pasquier, M.D.
From the Service d'Anatomie-Pathologique (R.B., D.P., B.P.), Centre Hospitalier Universitaire de Grenoble; the Institut Gustave Roussy (J.-C.S, M.-J.T-L.), Villejuif; and the Centre Léon Bérard (D.R., C.B.), Lyon, France.
Am J Surg Pathol 2000;24:830-836 Abstract quote Desmoplastic small round cell tumors (DSRCTs) present a reciprocal chromosomal translocation, t(11;22)(p13;q12), that results in fusion of Ewing's sarcoma and Wilms' tumor (WT1) genes.
The authors evaluated 15 DSRCTs and 71 other tumors often considered in the differential diagnosis for immunoreactivity using a polyclonal antibody directed against the WT1 part of the chimeric protein resulting from this translocation. WT1 immunostaining was performed on paraffin material using the WT(C-19) antibody after heat-antigen retrieval. All the DSRCTs (15 of 15, 100%) demonstrated strong WT1 nuclear immunoreactivity. Ten of 14 nephroblastomas (71%) disclosed WT1-positive nuclei in accordance with the staining reported by others, and rare and focal nuclear positivity was detected in two of 17 rhabdomyosarcomas. WT1 immunoreactivity was not observed in Ewing's sarcoma/primitive neuroectodermal tumors (zero of 21, 0%), neuroblastomas (zero of 17, 0%), or rhabdoid tumors of the kidney (zero of two, 0%).
In nephroblastoma, differential diagnosis with DSRCT was not difficult: Clinical and morphologic data are not similar for these two entities. The current study validates WT1 immunoreactivity as a useful marker to separate DSRCT from other small round cell tumors.
Desmin 100% (39/39) Cytokeratin (CAM5.2 and AE1/AE3) 95% (37/39) EMA 96% (24/25) Vimentin 81% (22/27) CD57 (Leu7) 67% (10/15) NSE 72% (18/25) Synaptophysin 16% (3/19) CYTOKERATIN NEGATIVE Cytokeratin-negative desmoplastic small round cell tumor: a report of two cases emphasizing the utility of reverse transcriptase-polymerase chain reaction.
Trupiano JK, Machen SK, Barr FG, Goldblum JR.
Department of Anatomic Pathology, The Cleveland Clinic Foundation, Ohio 44195, USA.
Mod Pathol 1999 Sep;12(9):849-53 Abstract quote
Desmoplastic small round cell tumor (DSRCT) is a unique, highly aggressive neoplasm that chiefly affects male adolescents and young adults. This tumor is characterized by nests of small undifferentiated cells that show immunohistochemical evidence of epithelial, mesenchymal, and neural differentiation.
We report two cases of DSRCT that lacked immunohistochemical evidence of epithelial differentiation, but were found to have the fusion transcripts characteristic of this tumor. Both patients (a 41-year-old male and a 31-year-old female) presented with large intra-abdominal masses.
After diagnostic biopsy, both were treated with multi-agent chemotherapy. One patient expired 18 days after diagnosis, and the other is currently alive 28 months later. Histologically, both tumors had the characteristic features of DSRCT and were composed of small round cells with hyperchromatic nuclei and scanty cytoplasm. In one of the cases, perinuclear intracytoplasmic hyaline inclusions were seen. Immunohistochemically, neither case expressed any of the epithelial markers tested, including AE1/AE3, CAM 5.2 and EMA. Both tumors were diffusely immunoreactive for desmin with a prominent globoid "dot-like" pattern of staining in one case. Both tumors stained for vimentin, neuron specific enolase, and synaptophysin, but were negative for CD99, muscle-specific actin, and myogenin. Reverse transcriptase-polymerase chain reaction revealed EWS-WT1 fusion transcripts characteristic of this neoplasm.
In conclusion, we describe two cases of DSRCT that lacked immunohistochemical evidence of epithelial differentiation but had histologic and other immunohistochemical features which suggested this diagnosis. The ability to confirm the diagnosis of this rare tumor using molecular genetic techniques is particularly useful in those cases with unusual histologic or immunophenotypic features.
DIFFERENTIAL DIAGNOSIS DESMOPLASTIC TUMOR WITH DIVERGENT DIFFERENTIATION Desmoplastic primitive neuroectodermal tumor with divergent differentiation. Broadening the spectrum of desmoplastic infantile neuroepithelial tumors.
Yachnis AT, Rorke LB, Biegel JA, Perilongo G, Zimmerman RA, Sutton LN.
Department of Pathology, Children's Hospital of Philadelphia, PA 19104.
Am J Surg Pathol 1992 Oct;16(10):998-1006 Abstract quote
We report an unusual large, multicystic, posterior fossa neuroepithelial neoplasm involving the cerebellum, brain-stem, and quadrigeminal cistern of a 9-month-old girl. The neoplasm consisted of variably sized, sharply demarcated nests of small cells with a high nuclear-cytoplasmic ratio and moderately basophilic nuclei, embedded in a desmoplastic, immature-appearing, mesenchymal stroma. The nests contained mitoses but none were seen in the stroma. Glial fibrillary acidic protein (GFAP), neurofilament protein, synaptophysin, and cytokeratin (AE-1) were expressed in the nests. Mesenchymal cells were negative for neural markers but positive for vimentin and desmin.
The neoplasm was interpreted as a mixed mesenchymal and primitive neuroectodermal tumor (PNET) with histologic features reminiscent of a recently described intraabdominal desmoplastic small cell tumor. The tumor responded poorly to chemotherapy and a second operation was performed 1 year later. The second specimen bore no resemblance to the original and consisted of epithelial-like nests and clusters of neoplastic cells frequently interrupted by sinusoidal vessels. Tumor cells had medium-sized vesicular nuclei with small nucleoli, and a granular cytoplasm. Occasional less cellular islands of neuropil-like tissue contained larger cells having eccentric, vesicular nuclei with prominent nucleoli and abundant pink cytoplasm. Mitoses were not conspicuous. Many cells expressed synaptophysin, neurofilament protein, and GFAP. Neurofilament protein was strongly positive in the larger, neuron-like cells and synaptophysin stained the neuropil-like areas strongly but was less prominent in the neuronal perikarya. Unexpectedly, the neuropil-like areas expressed epithelial membrane antigen, whereas the neuronal cells were negative for chromogranin A.
The peculiar histologic picture, combination of phenotypic markers, and remarkable biologic behavior of this unusual tumor defies classification according to existing nomenclature and exemplifies the broad range of phenotypes expressed by primitive neuro-epithelial neoplasms.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS Aggressive with a poor prognosis
5 Year Survival 16/22 patients dead within 8-50 months after initial therapy TREATMENT Due to the diffuse spread of the disease, complete surgical removal is often impossible
Multiagent chemotherapy with a multidisciplinary approach
GENERAL
The desmoplastic round cell tumor: a new solid tumor of childhood.Crombleholme TM, Harris BH, Jacir NN, Latchaw LA, Kretschmar CS, Rosenfield CG, Wolfe LC, Cendron M, Trask C, Wolfe HJ.
Department of Pediatric Surgery, Tufts University School of Medicine, Boston, MA.
J Pediatr Surg 1993 Aug;28(8):1023-5 Abstract quote Three patients with a new, pathologically distinct solid tumor of childhood have been treated recently. The disease is characterized by male predominance, adolescent onset, an extensive abdominal primary tumor, and aggressive metastases to regional lymph nodes, liver, and lung. Two patients presented with vague abdominal pain and the third with testicular pain.
All three noted fatigue and malaise of less than two months' duration with minimal associated weight loss. Computed tomography (CT) scans of the abdomen and chest were obtained for initial preoperative staging, and then all three underwent surgical exploration. Widespread disease was found in each case. In no instance was complete tumor extirpation possible because of extensive peritoneal spread and lymphatic and hepatic metastases.
Histologically, all three tumors consisted of round blue cells with a dense desmoplastic reaction and focal rhabdoid features. Immunohistochemical markers for epithelial, neural, and muscle elements were positive. Aggressive multidrug chemotherapeutic regimens were used in each case, and all three patients are alive and well but with known residual disease.
We conclude that in cases of the desmoplastic round cell tumor of childhood, CT scans underestimate the extent of disease, and exploratory laparotomy is necessary for diagnosis and appropriate staging. Surgery is usually palliative because of extensive spread. Awareness of this newly recognized aggressive solid tumor of childhood is essential to define its natural history and guide the development of effective multidisciplinary therapeutic regimens.
IRINOTECAN Successful clinical response to irinotecan in desmoplastic round blue cell tumor.
Rosoff PM, Bayliff S.
Division of Hematology-Oncology, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
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