Desmoplastic small round cell tumor of the pancreas: An unusual primary site for an uncommon tumor.

Pancreas is a rare location for desmoplastic small round cell tumor. The present case highlights the dilemma in diagnosis and ascertaining the site of tumor origin. Morphologic and immunohistochemical features were complemented with the molecular markers and tumor origin which was initially nebulous was subsequently confirmed on exploratory laparotomy.

INTRODUCTION

Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive neoplasm. It has a propensity for serosal surfaces, especially the peritoneal cavity, but usually without an organ base. Also the rarity and varying morphologic appearances of DSRCT often make it vulnerable for diagnostic errors.[12]

CASE REPORT

A 16-year-old girl presented with an asymptomatic abdominal lump which became apparent since the preceding one month. A computed tomography (CT) scan revealed a large lobulated heterogeneous mass extending from the splenic hilum to the dome of the urinary bladder measuring about 21 × 15 × 10 cm in its maximum cranio-caudal, transverse and antero-posterior extents [Figure 1]. The mass displaced the stomach, small bowel and abutted the pancreatic body and tail. No definite organ of origin could be determined due to the large size. However, it appeared to be arising from the retroperitoneum. The tumor volume was estimated to be 4205.8 cubic cm. A core biopsy revealed a malignant round cell tumor. The tumor cells expressed vimentin and Mic-2. The clinicopathological features favored a primitive neuroectodermal tumor (PNET). The metastatic work-up including bone marrow studies, bone scan, and CT scan of thorax was negative.

Figure 1

(a, b): Coronal and sagittal CT scan images showing a large lobulated mass occupying the gastro-splenic and gastro-pancreatic regions and extending inferiorly. Tortuous portal vein, SMV and splenic vein are noted

Combination chemotherapy was initiated as per the institutional protocol for PNET comprising of a six drug regimen of vincristine, doxorubicin, cyclophosphamide, actinomycin D, ifosfamide and etoposide. After the initial nine weeks of induction therapy, CT scan showed a persistent mass with no change in the extent of the disease.

On exploratory laparotomy, the mass was densely adherent to the greater curvature of the stomach and the transverse colon was draped over the anterior surface. After extensive and meticulous dissection, the mass was found to be arising from the body and tail of pancreas. Distal pancreatectomy with splenectomy and transverse colon resection was performed and the bowel continuity restored with an end-to-end colocolic anastomosis. Thorough search of the peritoneal cavity revealed a few peritoneal nodules on the posterior wall of the pylorus, porta, and peripancreatic region which were also resected.

Grossly, the mass measured 24 × 17 × 9 cm and the cut surface largely consisted of areas of necrosis with lobulated fleshy, white areas [Figure 2]. Microscopically, the tumor was composed of small round malignant cells with focal fibrous septa and necrosis. The tumor cells were also seen invading the intestine and the splenic hilum [Figure 3]. The portal and peripancreatic nodules also showed viable tumors. On immunohistochemistry, the tumor cells expressed desmin. Immunostaining with CD99 was equivocal and the cells showed cytoplasmic, but not nuclear, expression of WT1. The histologic and immunohistochemical features were overlapping with those of PNET and DSRCT. Hence molecular studies were performed. Reverse transcriptase polymerase chain reaction (RTPCR) using RNA extracted from formalin fixed paraffin embedded revealed EWS-WT1 gene fusion chimeric transcript, confirming a diagnosis of DSRCT. RT-PCR for EWS-FLI1 translocation was negative.

Figure 2

Gross specimen showing the mass along with spleen and transverse colon draped over it. Pancreatic stump is also seen (held with forceps)

Figure 3

a) A malignant small round cell tumor infiltrating the b) pancreas and c) the wall of the colon. d) Strong cytoplasmic positivity for antibody to desmin on immunohistochemistry. e) EWS-WT1 fusion transcript as demonstrated by RT-PCR

The patient received abdominopelvic radiotherapy along with concurrent chemotherapy following which maintenance chemotherapy was initiated. The patient developed intractable upper gastrointestinal bleeding manifested by hematemesis and melena, which significantly curtailed maintenance chemotherapy. The exact cause of the bleeding could not be ascertained but was attributed to the abdominopelvic radiotherapy. The patient, however, responded to prolonged conservative management and is now on regular follow-up with serial ultrasound examination. At 14 months from the last chemotherapy, the patient remained disease-free.

DISCUSSION

DSRCT is a rare and highly aggressive neoplasm described as a separate entity by Gerald and Rosai in 1989.[1] The exclusivity of DSRCT is due to its distinct clinical, histologic and immunophenotypic features and rarity, which makes it an often misdiagnosed neoplasm of children and adolescents.[2] It has a propensity for serosal surfaces, especially in the peritoneal cavity, characterized by the presence of large abdominal masses without any obvious organ base and widespread peritoneal involvement. However, the present case is unique, wherein the abdominal disease though extensive originated from the pancreas and infiltrated the colon, splenic hilum and greater curvature of the stomach; although, on critical review of the CT scan in retrospect, pancreatic origin could be conjectured it became apparent only on exploratory laparotomy [Figure 4]. Even though the extent of disease necessitated a substantial resection, a preoperative diagnosis of pancreatic origin would have helped in careful planning for the surgery considering the complex nature of surgery of the pancreas. A systematic review of indexed, English medical literature revealed only three previously published reports of DSRCT arising in the pancreas.[3-5]

Figure 4

Axial image shows the probable attachment of the mass to the pancreatic body and tail

The rarity of this tumor and the similarities it shares with other small round cell tumors makes the diagnosis challenging. It has a polyphenotypic immunostaining profile; however, the chromosomal abnormality is very specific for DSRCT.[6] In the present case, the diagnosis of DSRCT was confirmed with a positive EWS-WT1 fusion transcript on RT-PCR. An accurate diagnosis is essential in planning the therapy, anticipation of distinct tendencies (serosal spread) and importantly prognostication of the disease. Evidently this was not possible in the present case due to limitations in the initial diagnosis.

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.[7] 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 the present case, although contemporary curative treatment had been offered, but the treatment toxicity was a limiting factor in dispensing comprehensive therapy, thereby justifying the need for alternate less toxic treatment modalities.

In conclusion, although there were no misadventures in our case despite the lacunae, we reiterate the significance and advocate endeavor for achieving diagnosis and ascertaining the primary site of tumor origin.