Primary pancreatic Ewing sarcoma: a cytomorphologic and histopathologic study of 13 cases.

INTRODUCTION: Ewing sarcoma (ES) is a small, round cell sarcoma that rarely occurs in solid organs, including the pancreas. A diagnostic overlap exists with other primary pancreatic neoplasms, especially for specimens from small biopsies and fine needle aspiration (FNA). To improve the diagnosis of this rare pancreatic tumor, we have reported a series of 13 cases of primary pancreatic ES and reviewed the cytopathologic, surgical pathology, clinical, and radiologic features of these neoplasms. MATERIALS AND METHODS: We performed a retrospective case review of 13 patients with a diagnosis of pancreatic ES from 2 tertiary academic medical centers. A combination of cytology and histopathologic slides were reviewed, and the patient demographics, clinical information, somatic genetics, and radiologic findings were obtained from the electronic medical records. RESULTS: Five FNA specimens from 5 patients and 8 surgical biopsy or resection specimens were identified and reviewed. The patients included 9 males and 4 females, with a median age of 27 years (range, 15-78 years). The cytology smears were highly cellular and showed a combination of complex tissue fragments and singly dispersed small round blue cells. The final diagnosis was ES for all 5 FNA specimens in accordance with the characteristic cytomorphology, diffuse and/or strong membranous immunolabeling for CD99, membranous ß-catenin, and molecular confirmation of EWSR1 using fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction. CONCLUSIONS: The cytologic diagnosis of ES is challenging, especially in unusual locations such as the pancreas. However, the correct cytologic diagnosis is important because these patients will require neoadjuvant therapy before surgery. Confirmatory molecular studies should be required to render the diagnosis of pancreatic ES.

Review with novel markers facilitates precise categorization of 41 cases of diagnostically challenging, "undifferentiated small round cell tumors". A clinicopathologic, immunophenotypic and molecular analysis.

BACKGROUND: Despite extensive immunohistochemical (IHC) and molecular studies combined with morphologic findings, a group of round/ovoid cell tumors histologically similar to Ewing sarcomas (ES) but lacking EWSR1-rearrangements may remain unclassifiable. DESIGN: We retrospectively analyzed 41 Ewing-like tumors (formalin-fixed, paraffin-embedded) previously determined as negative or non-informative for EWSR1-rearrangements by FISH and/or RT-PCR. A new histopathology revision and additional IHC and molecular analyses were carried out in order to investigate whether additional IHC and/or molecular testing in combination with the morphological findings may help in reaching a definitive diagnosis. RESULTS: Almost all the tumors (n=40) involved soft tissue and/or bone and half the patients died of disease. In the archival cases all diagnoses were Ewing sarcoma (ES), Ewing-like sarcoma (ELS), myoepithelial tumor and undifferentiated sarcoma (US). In the new review all the tumors were re-classified as, ES (n=16), Ewing-like tumor with EWSR1 rearrangement and amplification and possible EWSR1-NFATC2 gene fusion (n=1), CIC-rearranged sarcomas or undifferentiated sarcoma, most consistent with CIC-rearranged sarcoma (n=7), sarcoma with BCOR-alteration or undifferentiated sarcoma, consistent with BCOR-associated sarcoma (n=3), neuroblastoma (n=2), unclassifiable neoplasm with neuroblastic differentiation (n=1), malignant rhabdoid tumor (n=2), lymphoblastic lymphoma (n=1), clear cell sarcoma of the gastrointestinal tract (n=1), small cell carcinoma (n=1), sclerosing rhabdomyosarcoma (n=1), desmoplastic small round cell tumor (n=1), malignant peripheral sheath nerve tumor (n=1), poorly-differentiated synovial sarcoma (n=1), Possible gastrointestinal stromal tumor/GIST with predominant round cells (n=1) and possible SMARCA4-deficient-sarcoma (n=1). NKX2.2, ETV4 and BCOR immunoreactivity was observed in all ES, CIC-rearranged sarcomas and sarcomas with BCOR alteration, respectively. CIC-rearrangement by FISH was observed in many of the CIC-rearranged sarcomas. CONCLUSION: Our analysis of 41 Ewing-like tumors confirms that there may be a significant pathological and IHC overlap among Ewing-like tumors, with prognostic and therapeutic impacts. Additional IHC (NKX2.2, ETV4 and BCOR) and molecular studies including FUS, CIC or BCOR analysis may support the final diagnosis when FISH or RT-PCR fail to detect EWSR1-rearrangements. Any molecular findings should always be interpreted in relation to the specific clinical and pathological context.

A case report of CIC-rearranged undifferentiated small round cell sarcoma in the cerebrum.

CIC-rearranged undifferentiated small round cell sarcoma (CIC-rearranged USRCS) is a recently established type of Ewing-like small round cell sarcomas, characterized by CIC gene rearrangement, most commonly CIC-DUX4 fusion. This report presents the second case of CIC-rearranged USRCS arising primarily in the cerebrum. A 64-year-old otherwise healthy woman presented with a 1 × 1 cm sized hemorrhagic subcortical tumor in the left temporo-parietal lobe. The tumor repeatedly recurred, and the patient underwent three surgeries, chemotherapy with doxorubicin and ifosfamide, and radiotherapy, as well as gamma knife surgery. Systemic examination revealed no other extracranial masses. Imprint cytology revealed small to moderate-sized round-to-ovoid tumor cells with mild pleomorphism and variations in size and shape. The nuclei contained finely granular chromatin, and some had easily-recognizable nucleoli. The tumor exhibited a mainly cytoplasmic pattern of CD99 immunostaining, rather than a diffuse membranous pattern. The tumor also exhibited diffuse positivity for calretinin and p16, as well as partial positivity for WT1 (nuclear and cytoplasmic staining pattern) and D2-40. FISH assessment showed CIC split signals. In conclusion, CIC-rearranged USRCSs can occur primarily in the cerebrum. It would be impossible to diagnose them through cytology alone, but cytology would be useful to rule out other small round cell brain tumors including gliomas, lymphomas, carcinomas, and germinoma. Immunohistochemical analysis including tests for CD99, calretinin, and WT1 would help to suggest CIC-rearranged USRCSs and distinguish them from Ewing sarcomas. Additionally, immunohistochemistry for p16 might be useful in the diagnosis. Diagn. Cytopathol. 2016;44:828-832. © 2016 Wiley Periodicals, Inc.

Response to vinorelbine and low-dose cyclophosphamide chemotherapy in two patients with desmoplastic small round cell tumor.

We report two cases of abdominal desmoplastic small round cell tumor (DSRCT) that showed a clinical response to the vinorelbine/low-dose cyclophosphamide combination that has been claimed to be effective for rhabdomyosarcoma. This observation may prompt further investigation into the activity of such a regimen in DSRCT patients with recurrent or refractory disease, with a view to a possible future role as maintenance therapy in controlling minimal residual disease in patients who achieve complete remission with intensive induction multimodality therapy.

Interventional radiology cases from the royal hospital for sick children, glasgow: percutaneous metal biliary stent placement for palliation of intra-abdominal desmoplastic small round-cell tumour in a child.

Percutaneous placement of metal biliary stents for palliation of malignant processes affecting the porta hepatis is a well established technique in adults. We describe a case where the technique has been used successfully to treat obstructive jaundice in a ten-year-old boy suffering from intra-abdominal desmoplastic small round-cell tumour.

Desmoplastic small round cell tumor presenting in the ovaries: report of a case and review of the literature.

Desmoplastic small round cell tumor is a recently recognized clinical entity with specific morphologic, immunocytochemical, and genetic features. Though this tumor is mostly described to involve serosal surfaces, we report a case with ovarian involvement. The clinical presentation and differential diagnoses as well as the treatment including aggressive surgical debulking and multiagent chemotherapy are discussed.

Pathology quiz: small cell osteosarcoma.

A 15-year-old black male presented with shortness of breath, leg weakness, and pain in his back and rib cage. Four years previously he had noticed a lump in his upper back and complained of pain when playing basketball, especially on contact to that area. Recently, the pain had become more constant and increased in intensity. This was associated with loss of control in his legs, weakness, and paraesthesia. General physical examination revealed a palpable mass in the right midline upper back. Laboratory results were within normal limits. Radiographic scans demonstrated a destructive soft tissue mass at T6 vertebral body with scattered stippled calcification (Figure 1). The patient underwent a biopsy followed by excision of the mass (Figure 2) and decompressive laminectomy with reconstruction.

Diagnostic imaging of primitive neuroectodermal tumour of the chest wall (Askin tumour).

OBJECTIVES: To describe the radiological features of primitive neuroectodermal tumour (PNET) of the chest wall (Askin tumour) at diagnosis and to analyse the radiological changes occurring as a consequence of treatment and during follow-up. MATERIALS AND METHODS: Nine children with histologically proven PNET were studied. At diagnosis, all patients underwent chest X-ray (CXR), chest CT and bone scintigraphy; three patients also had MR and three had US. During treatment and follow-up, CT was performed in all patients. RESULTS: CT demonstrated a solid heterogeneous chest wall mass in all children at diagnosis and six had a rib lesion. Small nodular densities in the extra-pleural fat were identified in three patients at diagnosis. US, performed in three patients, excluded tumour infiltration of the lung or diaphragm, which had been suspected on CT. On MR, the lesions showed high signal intensity in T1-weighted/proton-density images and intermediate/high signal intensity in T2-weighted images compared with muscle. Minimal chest wall involvement was demonstrated in one case by MRI. Extensive necrosis of tumour mass with pseudo-cystic appearance was documented in the five patients who underwent chemotherapy. Macroscopically complete resection was performed in five patients but there was early local recurrence after surgery in two, identified by CT in one and by MR in the other. CONCLUSIONS: PNET of the chest wall should be considered in a child with a chest wall mass. CT is valuable for evaluating tumour extension at diagnosis, the effects of chemotherapy and assessing tumour recurrence after surgery. However, CT can overestimate pleural, lung or diaphragmatic infiltration, which are better evaluated by US. MR was superior to CT in the evaluation of tumour extension in one of three patients and may be considered complementary to CT, particularly in very large chest wall tumours.

Gallium and thallium scintigraphy in pediatric peripheral primitive neuroectodermal tumor (Askin tumor) of the chest wall.

A 3.5-yr-old child presented with a large thoracic mass which showed avid accumulation of 67Ga and 201Tl was studied. Histology showed a peripheral neuroectodermal tumor of the chest wall typical of the malignancy described as the Askin tumor. The 201Tl studies were a more accurate method of following tumor response to therapy than 67Ga scintigraphy.