Gastroblastoma with a novel ACTB::GLI1 gene fusion in a 19-year-old male.

Gastroblastoma is a rare gastric biphasic tumor composed of mesenchymal and epithelial elements in variable proportions. These tumors usually arise in the gastric antrum of children and young adults and are reported to harbor a recurrent MALAT1::GLI1 fusion. Herein we report a case of gastroblastoma in a 19-year-old male who presented with intermittent epigastric abdominal discomfort. Antrectomy revealed a 5.6-cm multi-lobulated, tan-pink mass with solid and focally cystic areas involving the submucosa, muscularis propria, and subserosa. All tumor cells demonstrated immunoreactivity for GLI-1, CD56, and vimentin; epithelial elements expressed pancytokeratins (AE1/AE3 and Oscar), and mesenchymal cells demonstrated focal positivity for CD10. Next generation sequencing revealed a novel ACTB::GLI1 fusion without evidence of the recurrent MALAT1::GLI1 fusion. Nine months after surgery, the patient is well without evidence of recurrence or metastases. To our knowledge, this is the first case of gastroblastoma harboring this novel ACTB::GLI1 fusion.

Recommendations for Cell-Free DNA Assay Validations: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists.

Diagnosing, selecting therapy for, and monitoring cancer in patients using a minimally invasive blood test represents a significant advance in precision medicine. Wide variability exists in how circulating tumor DNA (ctDNA) assays are developed, validated, and reported in the literature, which hinders clinical adoption and may negatively impact patient care. Standardization is needed for factors affecting ctDNA assay performance and reporting, including pre-analytical variables, analytical considerations, and elements of laboratory assay reporting. The Association for Molecular Pathology Clinical Practice Committee's Liquid Biopsy Working Group (LBxWG), including organizational representation from the American Society of Clinical Oncology and the College of American Pathologists, has undertaken a full-text data extraction of 1228 ctDNA publications that describe assays performed in patients with lymphoma and solid tumor malignancies. With an emphasis on clinical assay validation, the LBxWG has developed a set of 13 best practice consensus recommendations for validating, reporting, and publishing clinical ctDNA assays. Recommendations include reporting key pre-analytical considerations and assay performance metrics; this analysis demonstrates these elements are inconsistently included in publications. The LBxWG recommendations are intended to assist clinical laboratories with validating and reporting ctDNA assays and to ensure high-quality data are included in publications. It is expected that these recommendations will need to be updated as the body of literature continues to mature.

Combining Panitumumab With Anti-PD-1 Antibody in Cutaneous Squamous Cell Carcinoma of the Head and Neck After Inadequate Response to Anti-PD-1 Antibody Alone.

Anti-epidermal growth factor receptor (EGFR) antibodies and anti-programmed cell death 1 protein (PD-1) antibodies have been used separately to treat metastatic cutaneous squamous cell carcinoma (cSCC). While two anti-EGFR antibodies have similar clinical activity, cetuximab is administered weekly, whereas panitumumab is administered every two weeks. This report details findings using panitumumab in combination with anti-PD-1 antibody in patients with relapsed refractory cSCC. Three consecutive patients with poor performance status and rapidly progressive recurrent cutaneous squamous cell carcinoma (cSCC) of the face or scalp signed informed consent to receive an anti-PD-1 antibody with the option to add panitumumab were there inadequate response. After 2, 5, and 7 cycles of anti-PD-1 antibody treatment, respectively, panitumumab was added and the combination was continued for 27, 7, and 5 cycles, respectively. Fatigue, rash, and hypomagnesemia were reported, consistent with expectations for either agent alone. All three patients achieved durable complete response. The favorable clinical outcomes support further evaluation of the combination of anti-PD1 and anti-EGFR antibodies to control refractory cSCC of the face or scalp. J Drugs Dermatol. 2021;20(8):901-904. doi:10.36849/JDD.6175.

Plaque-Like Dermatofibroma: Case Report of a Rare Entity.

A case of a well-demarcated plaque measuring 11 cm without satellites of several years' duration is presented. It showed typical histologic findings of dermatofibroma, prompting a diagnosis of plaque-like dermatofibroma. The relationship to multiple clustered dermatofibromas and plaque-like myofibroblastic tumor is discussed.

Concurrent Eosinophilic Solid and Cystic Renal Cell Carcinoma and Angiomyolipoma With Epithelial Cysts in the Setting of Tuberous Sclerosis Complex: A Rare Synchronous Occurrence of 2 Distinct Entities.

Eosinophilic solid and cystic renal cell carcinoma (ESCRCC) is a recently described distinct renal neoplasm known to occur almost exclusively in female patients with or without tuberous sclerosis complex (TSC). We report a case of ESCRCC with 2 synchronous angiomyolipomas, including 1 angiomyolipoma with epithelial cysts (AMLEC), a rare cystic variant of AML that typically arises sporadically in the absence of TSC, in a 46-year-old woman with TSC. Besides additional copy number alterations identified in ESCRCC via molecular karyotyping, we also report a unique histologic feature of TSC-associated ESCRCC previously not described in detail, with formation of semicircular multinucleated neoplastic giant cells engulfing an additional intact neoplastic cell, simulating emperipolesis. To the best of our knowledge, this is the first reported case of ESCRCC with concurrent AMLEC in a patient with TSC, confirmed through additional genetic testing showing a germline heterozygous mutation in TSC1. Awareness of ESCRCC helps avoid the pitfall of a diagnosis of unclassified renal cell carcinoma, a typically much more aggressive tumor.

Minocycline-Induced Hyperpigmentation Mimicking Aortic Dissection.

Minocycline-induced hyperpigmentation of tissues has been documented previously, but extensive cardiovascular involvement is rarely described in literature. We report a case of marked cardiovascular hyperpigmentation resulting from approximately 4 years of minocycline exposure. We will highlight how intraoperative differentiation of minocycline-induced hyperpigmentation from more sinister causes of discoloration led to the appropriate surgical management.

Association of microRNA expression with microsatellite instability status in colorectal adenocarcinoma.

MicroRNAs (miRNA), small noncoding RNAs, are potential diagnostic and prognostic markers, as well as therapeutic targets. miRNA profiles of colorectal carcinomas have not been studied extensively in the context of microsatellite instability (MSI) status. We therefore evaluated 55 paired colorectal adenocarcinomas (CRC) and non-neoplastic mucosa samples using a panel of 24 miRNAs selected by literature review and prior studies in our laboratory. Stem-loop reverse transcriptase quantitative (real-time) polymerase chain reaction assays were done on RNA extracted from formalin-fixed, paraffin-embedded tissue of resection specimens. When miRNA expression was compared with clinicopathologic features and MSI status, eleven miRNAs (miR-183, -31, -20, -25, -92, -93, -17, -135a, -203, -133b, and -223) were over-expressed in CRC relative to mucosa, and nine (miR-192, -215, -26b, -143, -145, -191, -196a, -16, and let-7a) were under-expressed in CRC. Relative expression of miR-92, -223, -155, -196a, -31, and -26b were significantly different among MSI subgroups, and miR-31 and miR-223 were overexpressed in CRC of patients with hereditary non-polyposis colorectal cancer syndrome (Lynch syndrome). Our findings indicate that miRNA expression in CRC is associated with MSI subgroups, including low MSI and HNPCC-associated cancers, and that miRNAs may have posttranscriptional gene regulatory roles in these MSI subgroups and possible effects on the clinicopathologic and biomarker characteristics.

Multiple ovarian cysts and oligomenorrhea as the initial manifestations of a gonadotropin-secreting pituitary macroadenoma.

OBJECTIVE: To report a case of a follicle-stimulating hormone (FSH)-secreting pituitary adenoma, which manifested with oligomenorrhea, dysmenorrhea, and multiple bilateral ovarian cysts. METHODS: We present a case report of a 29-year-old woman, including detailed laboratory, radiologic, and pathologic findings, who was diagnosed as having an FSH-secreting pituitary tumor. The pertinent literature is also reviewed. RESULTS: A 29-year-old woman, after experiencing oligomenorrhea and increasing abdominal girth for >1 year, presented with an acute abdomen. Ultrasonography revealed multicystic ovaries >15 cm in maximal diameter, causing bilateral adnexal torsion. After bilateral ovarian cystectomies, ultrasound study showed recurrence of the cysts. Relevant laboratory data were as follows: serum FSH 6.8 mIU/mL, luteinizing hormone 0.1 mIU/mL, prolactin 67 ng/mL, human chorionic gonadotropin <2 mIU/mL, progesterone 3.5 ng/dL, estradiol 237 pg/mL, thyrotropin 1.8 microIU/mL, testosterone <4 ng/dL, insulin 8.0 microIU/mL, and fasting plasma glucose 87 mg/dL. Magnetic resonance imaging (MRI) of the brain revealed a 2.5-cm pituitary mass, although the patient had no symptoms of pituitary dysfunction. Transsphenoidal removal of the mass was performed, and pathology studies were positive for FSH-secreting adenoma. Repeated MRI at 3 months showed an 0.8-cm residual tumor. The patient refused adjuvant radiotherapy. Regular menses resumed within 2 months postoperatively, and she later successfully became pregnant. Almost 3 years after treatment, the patient remained asymptomatic, results of pituitary function tests were normal, and follow-up MRI showed no signs of tumor regrowth. CONCLUSION: Although very uncommon, gonadotropin-secreting pituitary adenomas should be considered in the differential diagnosis of new-onset oligomenorrhea and dysmenorrhea, especially if associated with multicystic ovaries on ultrasound study, even in the absence of elevated levels of serum gonadotropins. Furthermore, we propose that it may be acceptable to withhold adjuvant radiotherapy in patients who are asymptomatic after transsphenoidal surgical excision of these tumors.