Synovial sarcoma: defining features and diagnostic evolution

PEComa: morphology and genetics of a complex tumor family ☆

The Universal Protein Resource (UniProt) provides a stable, comprehensive, freely accessible, central resource on protein sequences and functional annotation. The UniProt Consortium is a collaboration between the European Bioinformatics Institute (EBI), the Protein Information Resource (PIR) and the Swiss Institute of Bioinformatics (SIB). The core activities include manual curation of protein sequences assisted by computational analysis, sequence archiving, development of a user-friendly UniProt website, and the provision of additional value-added information through cross-references to other databases. UniProt is comprised of four major components, each optimized for different uses: the UniProt Knowledgebase, the UniProt Reference Clusters, the UniProt Archive and the UniProt Metagenomic and Environmental Sequences database. UniProt is updated and distributed every three weeks, and can be accessed online for searches or download at http://www.uniprot.org.

The universal protein resource (UniProt)

Epithelioid sarcoma (ES) is a rare, aggressive soft-tissue neoplasm of uncertain differentiation, characterized by nodular aggregates of epithelioid cells, which are immunoreactive to cytokeratins (CKs) and epithelial membrane antigen, and often for CD34. It has a propensity for multifocal disease at presentation, local recurrence, and regional metastasis. These are aggressive neoplasms with particularly poor prognosis after regional or distant metastatic disease, for which surgical resection is still the mainstay of treatment, and options for patients with metastatic disease remain undefined. There are 2 distinct variants: classic ES, which typically presents as a subcutaneous or deep dermal mass in the distal extremities of young adults and comprises nodular distributions of relatively uniform epithelioid cells with central necrosis, and the proximal variant, which has a predilection for proximal limbs and limb girdles and the midline of the trunk, which is composed of sheets of larger, more atypical cells with variable rhabdoid morphology. Both classic and proximal-type ESs are associated with the loss of SMARCB1/INI1 protein expression, but appear otherwise molecularly relatively heterogeneous. We review classic and proximal-type ES, discussing morphology, immunohistochemical and genetic findings, the differential diagnosis, and the future potential for targeted therapies.

Epithelioid Sarcoma: Diagnostic Features and Genetics.

Myoepithelial (ME) tumors of soft tissue and bone display a heterogeneous histologic spectrum and in about half of the cases harbor EWSR1 gene rearrangements Despite rare case reports, the prevalence of fused in sarcoma (FUS) gene abnormalities and its related fusion partners remains undetermined among ME tumors Therefore, we screened 66 EWSR1-negative ME tumors for FUS abnormalities by fluorescence in situ hybridization (FISH) In an index FUS-rearranged case, 3'-rapid amplification of cDNA ends (RACE) was applied to identify the fusion partner Results were further confirmed by reverse transcription-PCR, followed by FISH screening the entire cohort of FUS-rearranged and EWSR1-positive ME lesions lacking a known fusion partner The correlation between genotype and clinicopathological features was also investigated As a result, six (9%) FUS-rearranged cases were identified, spanning divergent age groups, tumor locations, and morphologic features A novel FUS-KLF17 fusion was identified by 3'-RACE in an 11-year-old girl with a foot lesion associated with locoregional metastases Three additional cases with FUS-KLF17 fusions were identified and one KLF17 rearrangement (63%) was found among the 16 EWSR1-positive cases tested The KLF17-related ME tumors affected younger patients and often exhibited trabecular growth in a myxohyaline stroma, but this genotype did not correlate with a malignant phenotype In conclusion, a small subset of ME tumors harbor FUS rearrangements, two thirds of them being associated with KLF17 fusion FUS FISH analysis is recommended in EWSR1-negative lesions in which a ME diagnosis is suspected KLF17 is also a rare gene fusion partner to EWSR1-rearranged ME tumors

/pdf/novel-fus-klf17-and-ewsr1-klf17-fusions-in-myoepithelial-5g65i4nekc.pdf

Novel FUS-KLF17 and EWSR1-KLF17 fusions in myoepithelial tumors.

Primary soft tissue myoepithelial tumours (METs) are rare. Recent studies have shown EWSR1 rearrangement in certain METs. We present clinicopathological, immunohistochemical and molecular features of 14 primary soft tissue METs. Fourteen tumours, five benign and nine malignant, occurred in 12 men and two women, with an age range of 18–60 years (mean, 39.2); in upper extremities, four (29 %); chest wall, three (21 %); paraspinal region, three (21 %); pelvis, two (14 %) and lower extremities, two (14 %). Tumour size varied from 2 to 21.6 cm (mean, 8.7). Microscopically, most tumours were at least focally circumscribed. Morphological heterogeneity was noted, commonest patterns being cord-like and diffuse arrangement of polygonal cells in a myxoid stroma. By immunohistochemistry, tumours were positive for epithelial membrane antigen (EMA) (10/12, 83 %), cytokeratin (CK)/MNF116 (3/12, 25 %), p63 (7/10, 70 %), CD10 (4/6, 67 %), calponin (6/6, 100 %), S-100P (11/13, 85 %), glial fibrillary acidic protein (GFAP) (6/12, 50 %), smooth muscle actin (SMA) (3/9, 33 %), INI1/SMARCB1 (6/10, 60 %), brachyury (0/11), CD34 (0/5) and vimentin (4/4, 100 %), implying 93 % positivity for at least one epithelial marker. EWSR1 gene rearrangement was detected in 3/6 (50 %) METs (one benign and two malignant) and in an eccrine porocarcinoma which was included for reasons of comparison. Outcome details were available for six patients all surgically treated; three tumours (two malignant and one benign) resected with unknown marginal status recurred; two patients died and a single patient with myoepithelial carcinoma, who underwent a wide excision, is disease-free. This study illustrates the wide morphological spectrum of soft tissue METs, including benign and malignant subtypes. EMA and S-100P are optimal markers that should be supplemented with broad spectrum keratins, such as AE1/AE3, along with p63, GFAP and calponin in case of need but the results must be correlated with morphological features. Brachyury is useful in separating parachordoma/myoepithelioma from chordoma. EWSR1 rearrangement mostly occurs in METs that are deep-seated, irrespective of benign or malignant behaviour. Most malignant METs are INI1 negative.

Histopathological, immunohistochemical and molecular spectrum of myoepithelial tumours of soft tissues

Purpose
Hemangiopericytoma is a rare tumor of CNS with potential for recurrence and widespread metastasis, even outside CNS with even rare involvement of spinal cord This case series presents five patients to evaluate the clinical presentation, radiological features, management, pathology and outcome of spinal hemangiopericytomas

Spinal hemangiopericytoma: an institutional experience and review of literature.

Essential interpretations of bioinformatics in COVID-19 pandemic.

Background: Primary mediastinal malignant germ cell tumour (PMMGCT) is rare with unsatisfactory prognosis and pose difficulty in management due to lack of guidelines. Methods: All cases of PMMGCT diagnosed and treated between years 2014 to 2018 were retrospectively evaluated for clinico-pathological features, multimodality treatment and follow up. Results: Among a total of five PMMGCT cases, three were seminomatous and two were non seminomatous tumour [Yolk- sac tumour (n-1) and Mixed tumour (n-1)]. Four of these cases were non - metastatic with locally advancement and another one presented with metastasis to supraclavicular lymph node. All patients received platinum based induction chemotherapy. Post-induction chemotherapy, two cases of non seminomatous tumours underwent surgery. Among the three seminoma cases, one patient showed complete metabolic response; one with metastasis succumbed to the disease and the in-operable case of seminoma received local radiotherapy. Conclusion: PMMGCT needs a multi-disciplinary approach for appropriate diagnosis and management. Clinicopathological features like tumour site, extension, histopathological type, tumour stage and serum tumour marker are necessary for prognostication and decision making of further treatment plan.

/pdf/primary-malignant-mediastinal-germ-cell-tumors-a-single-f6au2ejr8v.pdf

Mukund Sable

Papers

Histopathological, immunohistochemical and molecular spectrum of myoepithelial tumours of soft tissues

Spinal hemangiopericytoma: an institutional experience and review of literature.

Essential interpretations of bioinformatics in COVID-19 pandemic.

Primary malignant mediastinal germ cell tumors: A single institutional experience.

Megakaryocytic emperipolesis: A histological finding in myelodysplastic syndrome