Benign metastasizing fumarate hydratase (FH)-deficient uterine leiomyomas: clinicopathological and molecular study with first documentation of multi-organ metastases.

Leiomyoma is the most prevalent benign tumor of the female reproductive system. Benign metastasizing leiomyoma (BML) is a rare phenomenon that presents at distant sites, typically the lungs, exhibiting histopathological features similar to the primary uterine tumor in the absence of malignancy features in both. Fumarate hydratase-deficient uterine leiomyoma (FH-d UL) is an uncommon subtype among uterine smooth muscle tumors (0.5-2%), showing distinctive histomorphology and FH inactivation. The majority of FH-d ULs are sporadic, caused by somatic FH inactivation, while a minority of cases occur in the context of the hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome caused by germline FH inactivation. Metastasizing FH-d UL has not been well documented and might be under-reported. Here, we present two cases (21- and 34-year-old females) who presented with metastasizing FH-d UL after myomectomy/hysterectomy with histologically proven multiple lung metastases in both, in addition to multi-organ involvement in one case (cervical-thoracic lymph nodes, left kidney, perihepatic region, left zygomatic bone, and soft tissues). Pathological examination confirmed FH-d leiomyomas in the primary/recurrent uterine tumors, multiple lung lesions, and a renal mass. The minimal criteria for diagnosis of leiomyosarcoma were not fulfilled. Genetic testing revealed germline pathogenic FH variants in both cases (c.1256C > T; p.Ser419Leu in Case 1 and c.425A > G; p.Gln142Arg in Case 2). These novel cases highlight a rare but possibly under-recognized presentation of FH-d BML. Our study suggests that FH-d BML cases might be enriched for the HLRCC syndrome.

Leiomyomatous Lesions of the Colon: Two Case Reports with Radiological Features, Pathological Correlations, and Literature Review.

Colonic leiomyomatous lesions are smooth muscle tumors including both benign leiomyoma and malignant leiomyosarcoma. They usually occur in elderly and middle-aged groups. They are rare, representing 3% of all gastrointestinal leiomyomas. Descending and sigmoid colon are the most commonly affected segments of colon. Patients are usually asymptomatic but occasionally they may present with abdominal pain, hemorrhage, and intestinal obstruction. Radiological findings for these lesions are variable and overlapping with other diagnoses but usually manifest as large lesions with lobulated margins, extra-colic growth, and heterogeneous enhancement. Final diagnosis is achieved by tissue diagnosis in which immunohistochemistry is used to differentiate them from other types of mesenchymal tumors like gastrointestinal stromal tumor. A complete surgical/endoscopic resection is usually curative with an excellent prognosis in cases of benign leiomyoma. In cases of leiomyosarcoma, post-surgical chemotherapy and radiotherapy are usually needed with a five-year survival of about 50%. We report the radiological findings with pathological correlation and literature review of two cases of colonic leiomyomatous lesions that presented with nonspecific abdominal pain. The lesions were resected surgically and confirmed histopathologically as leiomyoma and leiomyosarcoma of the colon, respectively. To the best of our knowledge, these cases are the first of colonic leiomyomatous lesions to be reported in Oman.

Biallelic variants of the first Kunitz domain of SPINT2 cause a non-syndromic form of congenital diarrhea and tufting enteropathy.

Biallelic SPINT2 pathogenic variants cause a syndromic form of congenital diarrhea and enteropathy (OMIM 270420). To date, 35 patients have been reported and all presented with additional extra-intestinal features, apart from one case. We report on a 5-year-old girl who presented early in life with diarrhea and was found to have a novel homozygous variant in SPINT2. Pathological studies confirmed tufting enteropathy, and during her 5 years of life, she has not developed any extra-intestinal features. Molecular analysis detected a homozygous variant (NM_021102.4: c.203A>G (p. [Tyr68Cys]) in SPINT2. This is the first missense variant reported in the first Kunitz domain (KD1) of SPINT2 in humans. In vitro functional studies of this variant confirmed the deleterious effect leading to the loss of inhibitory activity of the intestinal serine proteases. This is the first description of SPINT2-related diarrhea in a patient who lived without long-term total parenteral nutrition. This study expands the clinical and molecular characteristics of SPINT2-related conditions.

Dermatofibrosarcoma Protuberans Mimicking Primary Breast Neoplasm: A case report and literature review.

Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing mesenchymal neoplasm of the dermis and subcutaneous tissues that has a low-to intermediate-grade malignancy. DFSP commonly involves the trunk and extremities, and very rarely the breast skin, mimicking a primary breast neoplasm with few reported cases in the literature. We report a 35-year old female patient who was referred to the Royal Hospital, Muscat, Oman in 2017, with a two-year history of a slow growing left breast lump. Assessment of the breasts with mammography revealed a lobulated lesion in the left-upper-inner quadrant with neither microcalcification nor architectural distortion, mimicking a benign lesion. However, on ultrasound, the lesion had suspicious features with increased vascularity and hence, it was categorised as breast imaging reporting and data system (BIRAD) IV. The patient underwent left breast wide local excision and the histopathological diagnosis was dermatofibrosarcoma protuberans.