Pleomorphic mastocytoma associated with loss of chromosome 5, PDGFRA, and HRAS mutations: A case of cutaneous mastocytosis with severe atypia and indolent behavior.

A 21-year-old female presented with a 5-year history of an erythematous papule on her right breast. The biopsy showed a dense, dermal nodular infiltrate, extending focally into the subcutaneous tissue. The infiltrate was composed predominantly of pleomorphic cells with bi-lobed, multi-lobed, horseshoe, or ring-shaped nuclei. There was a smaller subset of monomorphous cells characterized by a round, reniform, or elongated single-lobed nucleus. Accompanying cells included few foamy histiocytes, lymphocytes, and numerous scattered eosinophils. No necrosis, vascular invasion, or ulceration was present. The pleomorphic and monomorphic granular cells were positive for Giemsa stain as well as for tryptase, CD117, CD68, CD2, and CD30 immunohistochemistry and negative for S100, CD1a, myeloperoxidase, lysozyme, and CD56. Clinical examination was negative for any additional similar lesions and serum tryptase was within normal limits. The bone marrow was not biopsied. In addition, fluorescent in situ hybridization revealed multiple clones with loss of number 5 chromosome and PDGFRA and HRAS mutations. The lesion did not recur or progress after a 6-year clinical follow-up. To our full knowledge, we report the first case of pleomorphic mastocytoma with loss of chromosome 5 and PDGFRA and HRAS mutations.

The Texas Immuno-Oncology Biorepository, a statewide biospecimen collection and clinical informatics system to enable longitudinal tumor and immune profiling.

A detailed understanding of the molecular and immunological changes that occur longitudinally across tumors exposed to immune checkpoint inhibitors is a significant knowledge gap in oncology. To address this unmet need, we created a statewide biospecimen collection and clinical informatics system to enable longitudinal tumor and immune profiling and to enhance translational research. The Texas Immuno-Oncology Biorepository (TIOB) consents patients to collect, process, store, and analyze serial biospecimens of tissue, blood, urine, and stool from a diverse population of over 100,000 cancer patients treated each year across the Baylor Scott & White Health system. Here we sought to demonstrate that these samples were fit for purpose with regard to downstream multi-omic assays. Plasma, urine, peripheral blood mononuclear cells, and stool samples from 11 enrolled patients were collected from various cancer types. RNA isolated from extracellular vesicles derived from plasma and urine was sufficient for transcriptomics. Peripheral blood mononuclear cells demonstrated excellent yield and viability. Ten of 11 stool samples produced RNA quality to enable microbiome characterization. Sample acquisition and processing methods are known to impact sample quality and performance. We demonstrate that consistent acquisition methodology, sample preparation, and sample storage employed by the TIOB can produce high-quality specimens, suited for employment in a wide array of multi-omic platforms, enabling comprehensive immune and molecular profiling.

Leiomyoma of the urinary bladder: a cytogenetic study of a case.

We report the first case of a leiomyoma of the urinary bladder studied by cytogenetics. In comparison with cytogenetic changes of leiomyomas of other sites, the karyotype of the tumor was unusual: 47,XX,+7/89 approximately 93,XXXX,-1,+7,+7,add(12)(q23.4),+add(12)(q23.4),-18,-21,+idic(21)(p11.2),-22.

A clonal t(8;12)(p11.2;q24.3) as the sole abnormality in a solitary fibrous tumor of the pleura.

A case of solitary fibrous tumor of the pleura with the karyotype 46,XY,t(8;12)(p11.2;q24.3) is reported. Although rearrangement of 12q15 approximately 24 is a recurring abnormality in solitary fibrous tumors, rearrangement of chromosome 8 was previously unreported in these tumors.

Deletion (21)(q21.2q22.12) as a sole clonal cytogenetic abnormality in a lobular capillary hemangioma of the nasal cavity.

A clonal deletion (21)(q21.2q22.12) was detected as a sole cytogenetic abnormality in a lobular capillary hemangioma (pyogenic granuloma) of the nasal cavity. This finding supports a neoplastic, rather than reactive, nature for this lesion. To our knowledge, these rare lesions have not previously been studied by cytogenetics.

A clonal translocation (7;8)(p13;q11.2) in a leiomyoma of the vulva.

We present the first case of a vulvar leiomyoma studied by cytogenetics. The tumor formed a 3.0-cm periurethral nodule in a middle-aged woman and was positive for the muscle markers desmin and caldesmon, and for estrogen and progesterone receptors. Its karyotype was 46,XX,t(7;8)(p13;q11.2). This translocation has not been described in previously reported leiomyomas, regardless of their site of origin. The transcription factor PLAG1 gene at 8q12 was not altered by the translocation.

A clonal dic(16;21)(p13.1;p11.2)del(16)(q11.1), with gains of several chromosomes and monosomy 21, in a case of splenic hamartoma: evidence for its neoplastic, not hamartomatous, origin.

Cytogenetic examination of a case of splenic hamartoma led to the discovery of a clonal population with the karyotype 47 approximately 58,XX,+X,+4,+5,+5,+6,+10,+12,+14,der(16)dic(16;21)(p13.3;p11.2), dic(16;21)del(16)(q11.1),+17,+19,+20,-21. This finding is indicative of a neoplastic, not hamartomatous, origin for this lesion.

Primary myeloid sarcoma of the testicle with t(15;17).

The first case of acute promyelocytic leukemia presenting as a solitary testicular mass (myeloid sarcoma) that relapsed in the contralateral testicle is described. The neoplastic cells strongly expressed chloroacetate esterase, myeloperoxidase, CD33, CD43, and weakly, CD117. The presence of many azurophil granules and Auer rods was detected by electron microscopy. Translocation (15;17)(q22;q21.1) was revealed by cytogenetics and was verified by fluorescence in situ hybridization. Contralateral testicle is a favorite site for recurrence in a subset of testicular myeloid sarcomas. Subclassification of all cases of myeloid sarcoma ought to be attempted.

Overexpression of the BCL2 gene in a Sertoli-Leydig cell tumor of the ovary: a pathologic and cytogenetic study.

A case of virilizing ovarian Sertoli-Leydig cell tumor overexpressing the BCL2 gene and including a novel clonal chromosomal rearrangement of chromosome 18, der(5)t(5;18)(p13;q12),+6,+12, der(18)r(5;18)(p15.3p13;p11.3q12) is described. Further studies of these rare tumors are necessary to ascertain the significance of the findings.

Cardiac myxoma: a cytogenetic study of two cases.

Two cases of cardiac myxoma, each arising in the left atrium, are presented. One tumor contained the clonal abnormality i(17)(q10),der(20)t(1;20)(q21;q11.2) and the second tumor contained add (9)(p22),+12. Such rearrangements have not been previously reported in these tumors.

Unusual histologic variant of a low-grade fibromyxoid sarcoma in a 3-year-old boy with complex chromosomal translocations involving 7q34, 10q11.2, and 16p11.2 and rearrangement of the FUS gene.

Low-grade fibromyxoid sarcomas are rare, histologically deceptive, cytologically bland tumors that are infrequently encountered in pediatric patients. Our knowledge of histologic spectrum of these tumors is limited. A histologically unusual variant of a low-grade fibromyxoid sarcoma arising in a 3-year-old boy and containing islands of cohesive epithelioid cells is described. The diagnosis was, given the patient's age and the presence of epithelioid islands, very difficult and was verified by the presence of 3-way chromosomal translocations involving 7q34, 10q11.2, and 16p11.2 by rearrangement of the FUS gene and by immunoreactivity for mucin 4.

Pericentric inversion (12)(p12q13-14) as the sole chromosomal abnormality in a leiomyoma of the vulva.

We present a case of a leiomyoma of the vulva with karyotype 46,XX,inv(12)(p12q13-14). It is noteworthy that the breakpoint at 12q13 approximately q14 is flanked by the HMGA2 gene. Although the gene remained intact, the presence of HMGA2 protein in the neoplastic cells indicates that it became activated by the rearrangement. It is curious that activation of the HMGA2 gene, while not restricted to smooth muscle tumors, was so far found only in genital leiomyomata (uterus, vulva, vagina) and not in any smooth muscle tumors arising in extragenital locations.

CD99-positive large cell neuroendocrine carcinoma with rearranged EWSR1 gene in an infant: a case of prognostically favorable tumor.

The first case of large cell neuroendocrine carcinoma arising in an infant is presented. The tumor arose at the anal verge of a 1-year-old girl. The diagnosis of this CD99-positive tumor was supported by expression of epithelial (keratins, EMA, and Ep-CAM) and neuroendocrine (chromogranin A, synaptophysin, and neuron-specific enolase) markers and absence of immunoreactivity for Fli-1. No fusion of EWSR1 with FLI-1 or ERG was detected by polymerase chain reaction. However, the split of the EWSR1 gene was demonstrated by fluorescence in situ hybridization. This case adds to the few epithelial tumors in which an EWSR1 rearrangement was demonstrated. Because the tumor was initially misclassified as an extraskeletal Ewing's sarcoma, the patient was treated according to the Ewing's sarcoma treatment protocol. She remains free of tumor 8 years after initial diagnosis.