SMARCB1 (INI1) Deficient Tumours of the Uterine Cervix: Report of Two Cases, Including One Associated With an NTRK Fusion.

Pathogenic variants (mutations) and other molecular events involving subunits of the SWItch/Sucrose Non-Fermentable chromatin remodelling complex are common in a wide variety of malignancies. Many of these neoplasms are characterized by undifferentiated morphology. They arise at a variety of sites in the female genital tract but have rarely been reported in the uterine cervix. We report 2 primary cervical neoplasms arising in young women (ages 28 and 29 yr) exhibiting loss of nuclear immunoreactivity with SMARCB1 (INI1). In one case, which had a mixture of epithelioid and spindle cells, molecular studies revealed no SMARCB1 pathogenic variant, but showed a SPECCL1::NTRK 3 fusion, in keeping with an NTRK fusion sarcoma. The second case exhibited rhabdoid morphology and molecular testing confirmed a SMARCB1 pathogenic variant (c.425 T>G:p.(Leu142Ter) which, interpreted in conjunction with the morphology and immunohistochemistry, resulted in classification as a proximal-type epithelioid sarcoma. To our knowledge, this is the first reported cervical neoplasm exhibiting a SMARCB1 pathogenic variant and the first NTRK fusion sarcoma showing SMARCB1 protein loss. We discuss the diagnostic challenges and complexities of the molecular findings.

Cervical Small Cell Variant of Paraganglioma With Sarcomatous Transformation: Report of a Unique Case.

We report a unique primary cervical neoplasm in a 44-yr-old woman which we believe, based on the morphology and immunophenotype, represents an extremely unusual small cell variant of paraganglioma. This represents the first report of a primary cervical paraganglioma. Following chemoradiation treatment, the tumor underwent malignant transformation into an S100 and SOX10 positive sarcoma, morphologically and immunohistochemically resembling a malignant peripheral nerve sheath tumor, which we believe represents a sarcoma derived from the sustentacular cells of the paraganglioma. Mutational analysis detected a nonsense mutation of NF1 gene in the sarcoma. This further supports the diagnosis as both somatic and germline NF1 mutations have been associated with paragangliomas and malignant peripheral nerve sheath tumors. Targeted RNA sequencing (ARCHER, expanded sarcoma panel) covering many known genes implicated in sarcoma development, did not reveal any other molecular alteration (fusion or internal tandem duplication).

An audit of indications and complications associated with elective hysterectomy at a public service hospital in South Africa.

OBJECTIVE: To assess relationships between clinical indication for hysterectomy and postoperative histologic findings, and to audit complications of hysterectomy at the gynecologic surgical unit of a public-service hospital in South Africa. METHODS: Surgical indications and details, histologic findings, and postoperative course were reviewed and analyzed for 335 patients who underwent hysterectomy at Groote Schuur Hospital, Cape Town, South Africa, in 2007. RESULTS: Hysterectomy was performed abdominally in 265 patients (79.1%) and vaginally in 70 (20.9%) patients (5 of these procedures were laparoscopically assisted). The most common indication was fibroid-related menorrhagia (23%), followed by abnormal uterine bleeding (14.9%). The incidence of intraoperative complications was 6-fold greater among patients with malignant disease than among those with a benign condition (P=0.001). The incidence of postoperative complications was greater following abdominal rather than vaginal surgery, whether traditional or laparoscopic (P=0.02). CONCLUSION: Most hysterectomies were carried out abdominally rather than vaginally, in part because many patients presented with advanced cancer or other condition that warranted this approach. Because of resource constraints, patients with benign conditions were more likely to be offered surgery if they had a clearly defined condition.