Ewing sarcoma is a rare aggressive malignant round cell tumor, primarily presenting in bone and soft tissues. This study presents two cases of this tumor in unusual locations, one in right colon which presented with intussusception and other in ovary which presented clinically as carcinoma ovary. Both the cases showed histomorphology of primitive round cell tumor with characteristic immunohistochemical profile and was confirmed on molecular analysis. We aim to highlight the importance of considering Ewing sarcoma in the differential diagnoses in these locations as they have dismal prognosis with no standard treatment modality.
Keywords: Colon, Ewing sarcoma, ovary, primitive neuroectodermal tumor
|How to cite this article:
Modi S, Vasdev N, Gupta P, Goyal H. Ewing sarcoma arising in colon and ovary––Two rare sites of presentation. Indian J Pathol Microbiol 2022;65:433-6
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Modi S, Vasdev N, Gupta P, Goyal H. Ewing sarcoma arising in colon and ovary––Two rare sites of presentation. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 May 5];65:433-6. Available from: https://www.ijpmonline.org/text.asp?2022/65/2/433/343198
Ewing sarcoma (ES) and peripheral primitive neuroectodermal tumor (PNET) were originally regarded as distinct entities, but are now considered a single pathological entity as they share common cytogenetic alterations. Although primarily present in bone and soft tissues, some cases have been documented at unconventional sites. Herein we present two cases of ES, one in right colon and other in ovary, which form extremely uncommon sites for this tumor. Both cases presented with non-specific clinical manifestations and imaging findings, so it was quite challenging to diagnose and required molecular studies for confirmation.
32 years old male presented with complaints of pain abdomen. USG abdomen revealed a hypoechoic lesion near mesentery, followed by a CECT which revealed a colocolic intussusception with a polypoidal lesion at the leading edge. The patient underwent right hemicolectomy in August 2019.
Grossly, a nodular polypoidal intraluminal growth in the cecum and ascending colon was seen measuring 5 × 5 cm [Figure 1]a. Microscopically, the tumor comprised of nests and sheets of primitive round to oval tumor cells, involving all the layers [Figure 1]b and [Figure 1]c. One lymph node was involved (1/14). Immunohistochemically, the tumor cells were negative for CK and Vimentin, while positive for CD99, FLI 1 and synaptophysin, Ki67 was 30-40%. [Figure 2]. EMA, LCA, S 100, CD3, CD20, CD10, CD34, CD56, Chromogranin, Desmin, CD117, DOG1, CD30 and PLAP were negative. Diagnosis of Ewing sarcoma/PNET was suggested. Fluorescence in situ hybridization (FISH) was done which showed EWSR1 (22q12) translocation, thus confirming the diagnosis [Figure 5a]. PETCT ruled out any other metabolic active disease. Patient was started on chemotherapy with VAC-IE protocol (Vincristine, doxorubicin, cyclophosphamide alternating with Ifosfamide and etoposide) from November 2019. The patient is doing well till now post 12 cycles of chemotherapy.
|Figure 1: (a) Gross image revealing a polypoidal mass in cecum and ascending colon; (b) Sections reveal a malignant round cell tumor involving colonic wall (Hematoxylin and eosin, original magnification x 100); (c) nests of monotonous primitive round cells with inconspicuous nucleoli (Hematoxylin and eosin, original magnification x 200)|
|Figure 2: Immunohistochemical results of colonic tumor. (a) CK, negative (x100) (b) Vimentin, negative (x100) (c) CD99, diffuse membranous (x400) (d) FLI1, diffuse nuclear (x400) (e) Synaptophysin, focal (x400) (f) Ki67(x400)|
31 years old female presented with complaints of pain and abdominal distension for 1 month. PETCT revealed FDG avid bilateral adnexal masses, measuring 9.2 × 8.4 × 9.7 cm on right and measuring 2.0 × 2.0 × 3.4 cm on left with FDG avid omental thickening, peritoneal and serosal deposits with ascites, suggesting possibility of ovarian carcinoma [Figure 3]a and [Figure 3]b. Serum Ca125 was 602 IU/ml. Provisional diagnosis of Carcinoma ovary Stage III was made and the patient was administered 6 cycles of chemotherapy (Paclitaxel and Carboplatin). Serum Ca125 returned to normal. Post chemotherapy PETCT showed no significant treatment response. MRI findings showed enhancing marrow infiltrative lesions in multiple bones suggestive of metastatic lesions. Multidisciplinary tumor board discussion was done and surgery was advised.
|Figure 3: (a) PETCT highlighting ovarian mass, axial section; (b) PETCT, sagittal section. (c) Sections of right ovary revealing homogenous population of primitive round tumor cells (Hematoxylin and eosin, original magnification x 400) (d) tumor infiltrating small intestinal wall (Hematoxylin and eosin, original magnification x 200)|
The patient underwent laparoscopic assessment followed by cytoreductive surgery in June 2017. Grossly, left ovary appeared unremarkable and right ovary was enlarged and nodular with solid, yellowish-white cut surface. Segment of small intestine was densely adhered to left colonic segment with an intervening serosal mass. Multiple other serosal deposits and lymph nodes were isolated.
Microscopically, right ovary showed homogenous population of primitive round tumor cells in nests and sheets [Figure 3]c. Left ovary showed a 5 mm focus of similar tumor. The tumor was invading through serosa up to muscle coat of colon and up to mucosa of jejunum [Figure 3]d. Multiple serosal deposits seen. Lymph nodes were uninvolved.
Immunohistochemically, the tumor cells were diffusely positive for Vimentin, CD99, FLI-1 and CD56 while focally positive for CK and Pax8 [Figure 4]. CK7, CK20, CA125, ER, LCA, EMA, Synaptophysin, Chromgranin, PLAP, Inhibin, Calretinin and Desmin were negative.
|Figure 4: Immunohistochemical results of ovarian tumor. (a) Vimentin, diffuse positive (x400) (b) CD99, diffuse membranous (x400) (c) FLI1, nuclear (x400) (d) CD56, diffuse positive (x400) (e) CK, focal (x400) (f) Pax8, focal (x400) (g) Desmin, negative (x200) (h) EMA, negative (x200)|
Diagnosis of PNET was suggested. FISH analysis indicated the presence of EWSR1 (22q12) translocation, thus confirming the diagnosis [Figure 5]b.
|Figure 5: EWSR1 dual colour, break-apart probe showing EWSR1 gene rearrangement. (a) colon tumor (b) ovarian tumor|
The patient received six cycles of VAC-IE till November 2017. PETCT after chemotherapy showed progressive disease. She was then started on next line of chemotherapy i.e., Irinotecan/Temozolomide. The patient again presented with subacute intestinal obstruction. MRCP revealed hepatic parenchymal deposits with mass at porta hepatis. Despite all supportive measures, patient’s condition continued to deteriorate. She was lost to follow-up after December 2017.
Ewing family of tumors has traditionally been subclassified as classical ES and PNET, the latter showing varying degrees of neuronal differentiation. However, the term PNET is no longer included in the most recent WHO classification of tumors of soft tissue and bone as they share common cytogenetic alterations.
The majority of ES affect children and young patients with a male predominance. Though ES may involve any location, it primarily involves bone and soft tissues. Among other sites, ES may also arise in gastrointestinal and female genital tract. We are presenting two such cases in these locations.
To the best of our knowledge, only seven cases of colorectal ES/PNET have been reported with only two cases reported in right colon.,,,,,, We reviewed data of ES cases arising in colorectum [Table 1]. It included 6 males and 2 females with an average age of 36 years (range 17-59) and average tumor size of 8.4 cm. ES of colorectum has the characteristics of non-specific clinical manifestations, rapid development and poor prognosis.
ES/PNET can also involve female genital tract, most common site being ovary followed by uterine corpus. Only a small number of cases of ovarian ES/PNET have been reported in literature.
Ovarian ES/PNET are highly aggressive tumors that frequently cause diagnostic dilemma because of their rarity. Most of the reported cases in the literature were in advanced stages at the time of presentation. Involvement of pelvic cavity or distant metastasis to lung, bone and bone marrow are the most common ways of spread. Clinical stage is the most important prognostic factor and the outcome is generally poor.
Chao et al. reviewed 19 cases of ovarian PNET. Median age was 25 years (range 13-79) and median diameter was 13.4 cm (range 5-30). The main clinical manifestations were abdominal pain and/or abdominal distension and pelvic/abdominal mass.
The non-specific clinical presentations and imaging of ES arising in these unconventional visceral sites make early diagnosis and differential diagnosis very challenging. Making an accurate diagnosis is critical for optimal patient management and prognostication. Also there are no surrogate blood markers. Immunohistochemical positivity with CD99 and FLI1 is being used for the diagnosis of ES/PNET. Now, NKX2.2 gene, an important target of EWS-FLI1, is considered a valuable marker for PNET.
The genetic hallmark is the presence of a specific translocation t(11;22) (q24;q12), which is expressed in approximately 85% of cases, that fuses EWSR1 to FLI1 to generate EWSR1-FLI1 oncoprotein. In other cases, alternate translocations fuse EWSR1 to other ETS family members including ERG, ETV1, ETV4 or FEV.
Because of the rarity of ES/PNET in visceral locations, no standard treatment plan exists to date. ES is treated aggressively with combination chemotherapy, as well as surgical resection and/or radiation therapy for the primary tumor. Combination chemotherapy has traditionally included vincristine, doxorubicin, cyclophosphamide and dactinomycin. The addition of ifosfamide and etoposide to a standard regimen significantly improves the outcome for patients with non-metastatic ES.
ES/PNET arising in visceral sites is very rare and should be carefully identified and diagnosed in order to choose the best therapeutic approach. Documentation of more such cases would propel further research on their prognosis and treatment options.
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