The expanding clinical spectrum of desmoplastic small round-cell tumor: A report of two cases with molecular confirmation

The Expanding Clinical Spectrum of Desmoplastic Small Round-Cell Tumor: A Report of Two Cases With Molecular Confirmation ANGELIQUE N. WOLF, MD, MARC LADANYI, MD, GERSON PAULL, MD, JAMES E. BLAUGRUND, MD, AND WILLIAM H. WESTRA, MD Desmoplastic small round cell tumor (DSRCT) is an aggressive neoplasm characterized by a consistent histological appearance, a unique immunohistochemical profile, and a specific chromosomal translocation. DSRCT is also hallmarked by distinctive clinical features. Most tumors arise in adolescent or young adult males, present as bulky abdominal masses, and diffusely spread along the peritoneal surface. We report two cases of DSRCT that do not fit this typical profile. One case involved the abdominal cavity of a 76-year-old woman. The other case arose in the parotid of a 22-year-old man. Histologically, the tumors showed the characteristic features of DSRCT. Immunohistochemically, the tumors showed positivity for

cytokeratin, desmin, and neuron-specific enolase. Genetically, the tumors expressed the EWS-WT1 chimeric transcript. These two cases expand the differential diagnosis for poorly differentiated small-cell tumors that involve elderly patients or arise in the parotid. Moreover, they challenge the popular notion that DSRCT is a "blastomatous" tumor derived exclusively from the primitive mesothelium. HUM PATHOL30:430-435. Copyright © 1999 byW.B. Saunders Company Key words: parotid, sialoblastoma, desmoplastic round small-cell tumor, EWS-WT1. Abbreviations: DSRCT, desanoplastic small round cell tumor; CT, computed tomography; RT-PCR, reverse transcriptase pulymerase chain reaction.

Desmoplastic small round-cell tumor (DSRCT) is an aggressive, usually fatal tumor that was recently described as a distinct entity by Gerald and Rosai. 1,2 Although comprised of nondescript poorly differentiated r o u n d cells, DSRCT can be distinguished from other primitive r o u n d cell tumors on the basis of its unique combination of morphological, immunohistochemical, and genetic findings. Histologically, DSRCT is characterized by angulated nests of small cells embedded within a fibrotic stroma. 1 Immunohistochemically, DSRCT shows a rather unique immunohistochemical profile characterized by positivity for cytokeratin, desmin, and neuron-specific enolase. 1 At the cytogenetic level, DSRCT harbors a novel reciprocal translocation at t(11;22) (p13;q12), 3~ which has b e e n shown at the molecular level to represent a fusion of the EWS and WT1 genes. 4 DSRCT is also characterized by a distinctive clinical profile. 1,6Males are affected more cormnonly than females, at a ratio of approximately 4:1. Patients are affected during adolescence or early adulthood. The median patient age is approximately 21 years, and to our knowledge, only one well-documented case has been reported in a postmenopausal woman. 1,7 Finally, patients typically present with

widespread involvement of the abdomen or pelvis. DSRCT has a predilection for growth along the peritoneum, and organ involvement is an inconsistent and secondary phenomenon. Although DSRCTs sometimes arise in extraabdominal sites such as the tunica vaginalis or the pleura, s-l° they consistently maintain an intimate association with a mesothelial lining. Given its primitive appearance, its tendency for multidirectional differentiation, and its segregation to young individuals, DSRCT is often grouped with the family of pediatric neoplasms known as "small round-cell tumors." Some have appropriately stressed consideration of DSRCT in the differential diagnosis of small round-cell tumors of children and young adults, particularly those showing diffuse spread along mesothefial-lined cavities. 6 Although the histogenic origin of DSRCT is unclear, its association with mesotheliallined surfaces has pointed to the primitive mesothelium or submesothelial mesenchyrne as the tissue from which they most likely arise. 1,a° In essence, DSRCT is regarded as a "mesothelioblastoma."l We report two cases of DSRCT that expand the clinical spectrum of this tumor. One tumor arose in the pelvic/ abdominal cavity of a 76-year-old woman. The other case arose in the parofid of a 22-year-old man. These cases emphasize that the diagnosis of DSRCT should not be dismissed solely on the basis of unusual clinical features such as advanced patient age or primary involvement of a non-mesothelial-lined organ. Furthermore, the notion that DSRCTs invariably arise from primitive mesothelium or submesothelial mesenchyme should be reconsidered.

From the Departments of Pathology and Otolaryngology, Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD; the Departments of Pathology and Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY; and the Departments of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, CA. Accepted for publication November 18, 1998. Address correspondence and reprint requests to William H. Westra, MD, The Johns Hopkins Hospital, Department of Pathology, 600 North Wolfe St, Baltimore, MD 2128%6417. Copyright © 1999 by W.B. Saunders Company 0046-8177/99/3004-0012510.00/0

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CASE REPORTS Case 1 A 76-year-old woman was evaluated by a general surgeon for a right lower quadrant mass. On physical examination, a

DESMOPLASTiC SMALL ROUND-CELL TUMOR (Wolf et al) Postoperatively, the patient underwent one cycle of chemotherapy consisting of cisplatinum, adriamycin, and VP-16. She then declined additional therapy. The patient is alive with residual disease 10 months after surgery.

large n o n t e n d e r abdominal mass was palpated in the right lower quadrant. A computed tomographic (CT) scan of the abdomen and pelvis showed a 13 × 12-cm heterogeneous mass filling the pelvic cavity and extending into the lower abdominal cavity (Fig 1A). There was no evidence of paraaortic or iliac adenopathy. At laparoscopy, the mass appeared to be centered around the fundus of the uterus, and there was extensive spread along the peritoneal surface with encasem e n t of the cecum and appendix. Multiple satellite nodules were noted in the mesentery and along the peritoneal surface of the sigmoid colon. The tumor was surgically debulked.

Case 2 A 23-year-old man presented to an outside hospital with a slowly growing mass over the angle of the left jaw. A C T scan showed a 5 × 5-cm heterogeneous mass involving the superficial and deep lobes of the left parotid (Fig 1B). CT scans did not show any additional masses in the head and neck, chest, abdomen, or pelvis. At surgery, the mass was noted to be densely fibrotic and adherent to surrounding structures such that the facial nerve could not be identified. An incisional biopsy was performed. The patient was referred to The Johns Hopkins Hospital for further evaluation and treatment. Three cycles of chemotherapy were administered, consisting of cytoxan, adriamycin, and vincristine; this was followed by two cycles of ifosfamide and VP-16. Follow-up CT scans showed no significant change in the size of the mass and again did not show any masses in the abdomen or pelvis. A left radical parotidectomy with a left neck dissection was performed. At surgery, the tumor was centered in the parotid and extended into the surrounding soft tissues with encasement of the internal jugular vein and the spinal accessory nerve. The entire tumor was removed, although subsequent histological evaluation showed microscopic extension of tumor to the soft tissue margins. Postoperatively, the patient was treated with local radiation and an additional cycle of chemotherapy. The patient is alive and free of disease 10 months after surgery.

MATERIALS AND METHODS For both cases, tissues had been fixed in 10% neutralbuffered formalin, embedded in paraffin, and stained with hematoxylin and eosin. A representative tissue block of each case was selected for immunohistochemical studies and, in case 1, for molecular genetic analysis. Frozen tumor tissue was available in case 2 for molecular genetic studies. Immunoperoxidase studies were performed by the avidin-biotin-peroxidase technique. The tissue sections were incubated with the panel of antibodies shown in Table 1. Molecular studies were performed at the Memorial Sloan Kettering Cancer Center. Tumor RNA was extracted and reverse transcribed as previously described for frozen 4 and formalin-fixed and paraffin-embedded tissues. 11 RNA extracted from a well-characterized DSRCT, previously shown to harbor the EWS-WT1 gene fusion resulting from the reciprocal translocation at t(11;22) (p13;q12), served as a positive control. The forward primer for EWS exon 7 was 5'TCCTACAGCC&AGCTCCAAGTC-3'. The reverse primer for WT1 exon 8 was 5'-ACCTTCGTTCACAGTCCTTG-3'.4 Two types of negative controls were used: controls lacking RNA and controls lacking reverse transcriptase.

RESULTS FIGURE 1. Computed tomographic (CT) findings. (A) This CT scan of the pelvis (case 1) shows a large mass filling the pelvic cavity and displacing the pelvic structures to the left (arrows outline the mass). (B) This CT scan of the head (case 2) shows global and asymmetric enlargement of the left parotid (An asterisk indicates the center of the mass, and arrows outline its ill-defined border).

431

Morphological

Findings

T h e m o r p h o l o g i c a l f i n d i n g s were similar i n b o t h cases. Grossly, the t u m o r s were m u l t i n o d u l a r . B a n d s o f fibrosis s e p a r a t e d t u m o r n o d u l e s a n d e x t e n d e d i n t o the s u r r o u n d i n g soft tissues. T h e c u t surfaces were t a n a n d

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TABLE 1.

Volume 30, No. 4 (April 1999)

Antibodies Used in This Study Resul~

Antibody

Type

Source

Dilution

Case 1

Case 2

C y t o k e r a t i n (AEI:AE3) Epithelial membrane antigen Desmin Smooth muscle actin Neuron-specific enolase Chromogranin Synaptophysin O 1 3 (MIC2) S100 H M B 45

M M M M M M M M P M

Boehringer Mannheim, Indianapolis, IN DAKO, C a r p i n t e r i a , CA DAKO DAKO DAKO Boehringer Mannheim Boehringer Mannheim SIGNET, D e d h a m , M A DAKO DAKO

1:2000 1:1000 1:100 1:50 1:500 1:9000 1:50 1:400 1:6000 1:195

+ + + +++ + + + -

+ + + + +++ + + + -

A b b r e v i a t i o n s : M, m o n o c l o n a l ; P, p o l y c l o n a l .

nodular without grossly visible necrosis. The t u m o r from case 1 studded the peritoneal surface. T h e tumor from case 2 was centered in the parofid but e x t e n d e d into surrounding soft tissues. Microscopically, the tumors were composed of sharply outlined nests o f cells separated by zones o f fibrous and fibromyxoid stroma (Figs 2 and 3). Central necrosis was present in some o f the cellular islands. T h e t u m o r cells were closely packed and had r o u n d to oval nuclei without nucleoli. A subpopulafion o f cells in case 2 had a " r h a b d o i d " appearance. These cells were characterized by distention of the cytoplasm and displacement of the nucleus by eosinophilic inclusions. I m m u n o h i s t o c h e m i c a l Findings

T h e immunohistochemical findings are summarized in Table 1. In both cases, the tumor cells were immunoreacfive for cytokerafin, desmin, and neuronspecific enolase (Fig 3). Staining was strong and diffuse for desmin and neuron-specific enolase. Staining for cytokeratin was also strong but was present in a more patchy distribution. Most of the t u m o r cells showed a diffuse cytoplasmic pattern of staining for these mark-

ers. A perinuclear dot-pattern o f desmin positivity was not prominent. T h e t u m o r cells were focally immunoreactive for epithelial m e m b r a n e antigen. T h e t u m o r cells were not immunoreacfive for acfin, chromogranin, synaptophysin, O13 (MIC2), HMB-45, or S-100. M o l e c u l a r G e n e t i c Findings

Fusion of the EWS and WT1 genes results in the expression of a chimeric transcript. Detection of the chimeric transcript by reverse transcriptase polymerase chain reaction (RT-PCR) is a specific aid in confirming the diagnosis of DSRCT) 2,13Moreover, RT-PCR also can detect the chimeric transcripts from tissues fixed in formalin and e m b e d d e d in paraffin provided that the amplification targets are small (less than 200 base pairs).11 Using a primer from exon 7 o f EWS and an antisense primer from exon 8 of WT1, the 103-base-pair EWS/WT1 chimeric amplification p r o d u c t was detected in both cases using RNA extracted from a paraffin block in case 1 (Fig 4A) and from frozen tissue in case 2 (Fig 4B). T h e same 103-base-pair amplification product was also present in control tissue from a DSRCT previously

FIGURE 2. (A) The tumor from case 2 infiltrates the parotid parenchyma. (B) The tumor is composed of nests of small and round tumor cells embedded within a fibrotic stroma. 432

DESMOPLASTIC SMALL ROUND-CELL TUMOR (Wolf et al)

FIGURE 3. Immunohistochemical findings (case 1). (A) Nests of tumor celts are separated by a desmoplastic stroma (hematoxylin and eosin). The tumor cells are immunoreactive for (B) keratin (AE 1:AE3), (C) neuron-specific enolase, and (D) desmin.

A

-RT M

I

1

2

+RT 3

I

I

4

5

B 6

I

1

310~ 281 234 194 118~

2

3

-.,e,,,l

FIGURE4. Reverse transcriptase-polymerase chain reaction analysis of tumor RNA for the EWS-WT1 chimeric transcript. (A) Case 1. The size of DNA fragments (M) are shown in base pairs, Reverse transcriptase (RI") was a d d e d in lanes 4 through 6 (+RY), but it was not a d d e d in lanes 1 through 3 (-R1), Lanes 1 and 4: Negative control lanes with no RNA added. Lanes 2 and 5: Positive control lanes showing the standard 103-bp product obtained from a previously characterized desmopiastic small round-cell tumor (DSRC1) amplified with this primer pair. Lanes 3 and 6: Tumor RNA extracted from case 1, The arrow indicates the position of the amplification product. (B) Case 2. Lane 1: Negative control lane with no RNA added. Lane 2: Positive control lane showing the standard 103-bp product obtained from the previously characterized DSRCTamplified with this primer pair. Lane 3: Tumor RNA extracted from case 2. The arrow indicates the position of the amplification product.

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shown to express the EWS/WTI chimeric transcript by RT-PCR analysis of a fresh-frozen sample of this tumor.

DISCUSSION In 1991 Gerald et aP detailed the pathological and clinical findings of a desmoplastic small round-cell t u m o r (DSRCT). As additional cases were published, it became increasingly clear that the clinicopathologic spectrum of this t u m o r was broader than initially appreciated. We r e p o r t two cases that considerably expand the clinical scope o f DSRCT. One case involved a patient who was 76 years of age. The other case arose in the parotid, an organ far removed from the abdominal cavity and entirely unassociated with a serosal lining. The morphological and immunohistochemical features of DSRCT were well developed in both cases, and both tumors expressed the typical EWS/WT1 chimeric transcript. The presence of this chimeric transcript is highly specific for DSRCT. DSRCT almost invariably arises in adolescents or young adults. In their comprehensive literature review, Kretschmar et al 6 reports that the median age of 101 reported patients was 21 years, and the oldest patient was 38 years. T h e predilection of these tumors for young patients has firmly e n t r e n c h e d DSRCT as a m e m b e r of the "small round-cell tumors," a family of neoplasms sharing a small round-cell morphology and a tendency to concentrate in the pediatric population. Accordingly, DSRCT is now included in the expanding differential diagnosis of small round-celt tumors of children and young adults. 6 At the same time, DSRCT should not be eliminated from the differential diagnosis solely on the basis of advanced patient age, particularly for tumors showing diffuse spread along mesotheliallined cavities. Mead et al 7 reported a DSRCT involving the abdominal cavity of a 52-year-old postmenopausal woman, and we now r e p o r t a DSRCT involving the abdominal/pelvic cavity of a 76-year-old woman. If not considered in the differential diagnosis, these DSRCTs involving older patients might easily be confused with other types of adult neoplasms such as malignant mesothelioma and poorly differentiated carcinomas of Mfillerian origin. Parkash et aP ° speculated that some DSRCTs may have been previously misclassified as small cell mesotheliomas. This conjecture is certainly strengthe n e d by the finding that DSRCT sometimes can involve the same adult patient population that is affected by malignant mesotheliomas. In postmenopansal women, DSRCT might readily be mistaken for undifferentiated ovarian carcinomas of the surface epithelium. 7 Like ovarian carcinomas, DSRCTs sometimes present as ovarian masses and can even produce CA 125. 7,14,1~ Although most DSRCTs arise within the abdominal/ pelvic cavity, origin outside of the abdominal cavity is well recognized. Most of these extra-abdominal tumors are located in the tunica vaginalis or the pleura and, like their intra-abdominal counterparts, are intimately associated with a serosal membrane. 8~° We report the first case of DSRCT to arise within the parotid, a site not related to a mesothelial-lined surface. Evidence suggests

434

that this t u m o r originated in the parotid rather than metastasized from an abdominal or pelvic site. First, metastatic spread to the head and neck is u n c o m m o n for DSRCT. Head and neck involvement has been reported only when there is widespread t u m o r dissemination, and in such cases, head and neck implants typically involve cervical lymph nodes, s,16,17 A solitary metastasis to the parotid has not been reported. Second, extensive imaging studies and nearly 1 year of close patient follow-up have failed to uncover a primary neoplasm elsewhere. The differential diagnosis for DSRCT routinely encompasses the Ewing's sarcoma/primitive neuroectodermal t u m o r group, embryonal and alveolar rhabdomyosarcoma, neuroblastoma, and malignant lymphoma. When DSRCT arises within an organ, the differential diagnosis is e x p a n d e d in a site-specific fashion. In the salivary glands, DSRCT must be distinguished from solid variant of adenoid cystic carcinoma and primary or metastatic small cell undifferentiated carcinoma. In most cases, careful integration of the clinical, histological, and immunohistochemical findings should allow distinction of DSRCT from these o t h e r tumors. For example, small cell undifferentiated carcinoma, either of primary salivary gland origin or metastatic from some other site, occurs in older patients. Unlike DSRCT, small cell carcinoma lacks immunohistochemical staining for desmin but often stains for specific markers of n e u r o e n d o c r i n e differentiation (eg, chromogranin, synaptophysin, and Leu 7), In the solid variant of adenoid cystic carcinoma, the focal but consistent presence of cribriform or tubular growth patterns usually permits distinction from DSRCT at the microscopic level. Care should be taken not to confuse DSRCT and adenoid cystic carcinoma based on immunohistochemical findings. Both tumors may be immunoreactive for cytokeratin, desmin, and neuron-specific enolase; but adenoid cystic carcinomas do not show the dotlike pattern of desmin staining, and cytokeratin staining is either weak or negative in the solid areas, is,l° The consistent association of DSRCT with the mesothelium and submesothelial mesenchyme has provided very compelling evidence for the mesothelial origin of DSRCT. The notion that DSRCTs exclusively arise from a mesothelial-lined surface, however, was u n d e r m i n e d by two recent reports of DSRCT occurring in sites entirely unrelated to a mesothelial-lined surface. Tison et al 2° reported a t u m o r arising in the posterior cranial fossa, and Antonescu et a121 reported a t u m o r involving the bone and soft tissues of the right hand. We now report the third case o f a DSRCT arising in a site far removed from a mesothelial lining. Although DSRCT appears to arise from undifferentiated cells with a potential for simultaneous differentiation along multiple lines, these cells may be less site restricted than previously supposed. Primitive analog-type tumors of the salivary glands are referred to as sialoblastomas. 22-24 Like DSRCT, sialoblastoma is characterized by nests of primitive basaloid cells set in a fibrous or fibromyxoid background. Taylor2~ argued that sialoblastomas originate

DESMOPLASTIC SMALL ROUND-CELL TUMOR (Wolf et al)

from the primitive blastema and, like blastomas arising in other organs, are capable of differentiation along more than one cell line. By this definition, DSRCT of the parotid gland could be conceptualized as a form of malignant sialoblastoma. Classic sialoblastoma, however, differs from DSRCT clinically and pathologically. Sialoblastoma is generally seen at or shortly after birth, but not in adolescents or young adults. At the morphological and immunohistochemical levels, sialoblastomas, to some degree, resemble fatal salivary gland tissue and show mixed ductal and myoepithelial elements. Sialoblastomas show varying degrees of tumor differentiation and clinical aggressiveness, and it is likely that the term sialoblastoma (or " e m b r y o m a " ) has been used to encompass a diverse group of tumor types. Some have proposed that sialoblastoma be divided, at the very least, into benign and malignant s u b t y p e s . 22,23 Could other examples of DSRCT have been previously published as malignant sialoblastomas? We have found no convincing evidence to support this possibility. Malignant primitive salivary gland tumors are exceedingly rare in adolescents and young adults. In their review of 73 salivary gland tumors in children and young adults collected over a 17-year period, Donath et a126 identified only one malignant "embryonal" salivary gland carcinoma. This particular tumor arose in the parotid o f a 12-year-old boy, had a primitive morphological appearance, and behaved in a highly aggressive fashion, but it does not resemble DSRCT on review of the published microscopic, immunohistochemical, and ultrastructural findings. 26 Too few cases are available to establish whether DSRCTs arising within viscera are associated with the same dismal prognosis as their counterparts in the abdomen, where bulky tumor growth and diffuse peritoneal spread render complete surgical removal unattainable. Earlier presentation of more superficially located tumors and the absence of diffuse serosal spread may translate into a higher likelihood of complete surgical removal and extended disease-free survival. Our one patient with a parotid-based tumor remains free of recurrent disease 10 months after surgery. Acknowledgment. T h e a u t h o r s t h a n k William G e r a l d for critical r e a d i n g o f t h e m a n u s c r i p t , P e d r a m A r g a n i f o r assisting with t h e figures, a n d A i m e e H a m e l i n for t e c h n i c a l assistance.

REFERENCES 1. Gerald WL, Miller HK, Battifora H, et al: Intra-abdominal desmoplastic small round-cell tumor. Am J Surg Pathol 15:499-513, 1991 2. Gerald WL, Rosai J: Desmoplastic small cell tumor with divergent differentiation. Pediatr Pathol 9:177-183, 1989 3. Biegel JA, Conard K, Brooks JJ: Translocation (11:22) (p13; q12): Primary change in intra-abdominal desmoplastic small round cell tumor. Genes Chromosom Cancer 7:119-121, 1993

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4. Ladanyi M, Gerald WL: Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor. Cancer Res 54:2837-2840, 1994 5. Sawyer JR, Tryka AF, Lewis JM: A novel reciprocal chromosome translocation t(11;22) (p13;q12) in an intraabdominal desmoplastic small round cell tumor. A m J Surg Patho116:411-416, 1992 6. Kretschmar CS, Colbach C, Bhan I, et al: Desmoplastic small cell tumor: A report of three cases and a review of the literature. J Pediatr Hematol Oncol 18:293-298, 1996 7. Mead M, Jones MA, Decain M, et al: Intra-abdominal desmoplastic small round-cell tumor in a postmenopausal female: Report of a case and review of the literature. EurJ Gynaecol Oncol 15:267-271, 1994 8. Cummings OW, Ulbright TM, Young RH, et al: Desmoplastic small round cell tumors of the paratesticular region: A report of six cases. AmJ Surg Patho121:219-225, 1997 9. Furman J, Murphy WM, Wajsman Z, et al: Urogenital involvement by desmoplastic small round-cell tumor. J Urol 158:1506-1509, 1997 10. Parkash V, Gerald WL, Parma A, et al: Desmoplastic small round cell tumor of the pleura. AmJ Surg Pathol 19:659-665, 1995 11. Argani P, Zakowski MF, Klimstra DS, et al: Detection of the SYT-SSX chimeric RNA of synovial sarcoma in paraffin-embedded tissue and its application in problematic cases. Mod Pathol 11:65-71, 1998 12. Argatoff LH, O'Connell JX, Mathers JA, et al: Detection of the EWS/WI'I gene fusion by reverse transcriptase-polymerase chain reaction in the diagnosis ofintra-abdominal desmoplastic small round cell tumor. AmJ Surg Patho120:406-412, 1996 13. de Alava E, Ladanyi M, RosaiJ, et al: Detection of chimeric transcripts in desmoplastic small round cell tumor and related developmental tumors by reverse transcriptase polymerase chain reaction: A specific diagnostic assay. A m J Pathol 147:1584-1591, 1995 14. Ordonez NG, Sahin AA: CA 125 production in desmoplastic small round cell tumor: Report of a case with elevated serum levels and prominent signet ring morphology. HUM PATHOL 29:294-299, 1998 15. Zaloudek C, Miller TR, Stern JL: Desmoplastic small cell tumor of the ovary: A unique polyphenotypic tumor with an unfavorable prognosis. IntJ Gynecol Patho114:260-265, 1995 16. Amato RJ, EllerhorstJA, Ayala AG: Intraabdominal desmoplastic small cell tumor: Report and discussion. Cancer 78:845-851, 1996 17. PratJ, Matias-Guiu X, Algaba F: Desmoplastic small roundcell tumor. A m J Surg Patho116:306-307, 1992 18. Chen JC, Gnepp DR, Bedrossian CW: Adenoid cystic carcinoma of the salivary glands: An immunohistochemical analysis. Oral Surg Oral Med Oral Patho165:316-326, 1988 19. Takahashi H, Tsuda N, Fujita S, et al: Immunohistochemical investigation ofvimentin, neuron-specific enolase, alpha 1-antichymotrypsin and alpha 1-antitrypsin in adenoid cystic carcinoma of the salivary gland. Acta PatholJpn 40:655-664, 1990 20. Tison V, Cerasoli S, Morigi F, et al: Intracranial desmoplastic small-cell tumor: Report of a case. A m J Surg Pathol 20:112-117, 1996 21. Antonescu CR, Gerald WL, Magid MS, et al: Molecular variants of the EWS-WT1 gene fusion in desmoplasfic small round cell tumor. Diagn Mol Pathol 7:24-28, 1998 22. Batsakis JG, Frankenthaler R: Embryoma (sialoblastoma) of salivary glands. Ann Otol Rhinol Laryngo1101:958-960, 1992 23. Harris MD, McKeever P, RobertsonJM: Congenital tumours of the salivary gland: A case report and review. Histopathology 17:155-157, 1998 24. Hsueh C, Gonzalez-Crussi F: Sialoblastoma: A case report and review of the literature on congenital epithelial tumors of salivary gland origin. Pediatr Pathol 12:205-214, 1992 25. Taylor GP: Congenital epithelial tumor of the parofid: Sialoblastoma. Pediatr Pathol 8:447-452, 1988 26. Donath K, Seifert G, LentrodtJ: The embryonal carcinoma of the parotid gland: A rare example of an embryonal tumor. Virchows Arch 403:425-440, 1984