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A 72-year-old man presented with weakness, lightheadedness, and weight loss. He had an episode of loss of consciousness 7 days prior to his presentation. Physical exam showed pallor and splenomegaly. Laboratory evaluation revealed anemia and leukopenia. A peripheral blood smear revealed hypochromic red blood cells with dacrocytes and few schistocytes. A bone marrow biopsy was performed and was hypercellular, with a relative increase in blasts. Megakaryocytes were mildly increased and showed dysplastic features. Mature erythroid and myeloid elements were present in decreased numbers. Flow cytometry showed 16% myeloid blasts. The gated population was positive for CD11C, CD13, CD33, CD34, CD38, and CD117 and partially positive for cytoplasmic myeloperoxidase. The combined immunophenotypic and morphologic analysis was consistent with a high-grade MDS of the MDS-EB2 (previously RAEB-2) type. Cytogenetic and FISH analyses revealed monosomy 7, as well as a t(3;8) rearrangement with a MYC-EVI1 rearrangement. The patient showed poor response to treatment and remained transfusion dependent. Following recurrent hospitalizations and no improvement, he declined further treatment and elected to receive home hospice care. MYC, a transcription factor located on chromosome 8q24.1, is involved in the expression regulation of 15% of human genes. EVI1, located on chromosome 3q26.2, is a transcription factor essential for regulation of self-renewal of hematopoietic stem cells and is one of the dominant oncogenes associated with myeloid leukemia. MYC rearrangements are a rare event in myeloid neoplasms, and the EVI1-MYC fusion has not yet been described to our knowledge. Both genes, when involved in hematologic malignancies, are associated with poor response to treatment and worse prognosis. This translocation may represent a small subset of cases with an aggressive clinical course, possibly requiring early identification, personalized treatment, and close follow-up

Mammary myofibroblastoma is a benign spindle cell tumor that can show variable morphologic patterns and lines of differentiation. Diffuse and strong immunohistochemical expression of CD34 is a characteristic of myofibroblastoma and greatly aids in confirming a diagnosis. Myofibroblastoma has been shown to belong to a family of CD34-positive tumors with similar morphology that show a deletion of 13q14, which includes RB1 and FOXO1A genes. The purpose of this study was to better understand a subset of myofibroblastomas that is characteristically CD34-deficient by immunohistochemistry. Six myofibroblastomas were studied by immunohistochemistry and fluorescence in situ hybridization (FISH) for RB1. Patients included five women and one man, aged 41-85 years (median, 52.5). Tumor size ranged from 0.4 to 1.5 cm (mean, 0.95). Tumors showed spindle cell morphology in five cases and epithelioid features in one case. Two tumors showed complete lack of CD34 staining. The remaining showed weak focal or weak patchy CD34 staining. Dichotomous staining was seen in one case with CD34-positive spindle cell areas and CD34-negative myxoid areas. All six tumors showed ER expression, five of six showed desmin expression, and four of six showed bcl-2 positivity. Two of six (33.3%) tumors showed deletion of RB1 by FISH, including one that showed loss of Rb immunohistochemical staining. Myofibroblastomas uncommonly show absent/focal expression of CD34, a potential diagnostic pitfall, particularly in small samples. Characteristic staining with other immunohistochemical markers is seen which can aid in confirming the diagnosis. These tumors may harbor deletion of RB1, similar to CD34-positive myofibroblastomas, and this deletion may not correlate with loss of Rb by immunohistochemistry.

Mammary myofibroblastoma is a benign spindle cell tumor that can show variable morphologic patterns and lines of differentiation. Myofibroblastoma belongs to a family of CD34-positive tumors with similar morphology that show a deletion of 13q14, which includes RB1 and FOXO1A genes. A subset of these tumors demonstrates distinct smooth muscle differentiation. We aimed to characterize 4 cases of the leiomyomatous variant of myofibroblastoma arising in the breast by clinicopathological, immunohistochemical, and molecular means. All 4 examples arose in women aged 41 to 62 years (median, 46.5 years). Tumors ranged in size from 1.7 to 2.5 cm (median, 2.2 cm). Morphologically, all tumors were characterized by bundles of smooth muscle cells with elongated cigar-shaped nuclei and eosinophilic cytoplasm. All 4 tumors showed diffuse positive staining with desmin, caldesmon, smooth muscle actin, estrogen receptor, and Bcl-2. CD34 staining was diffusely positive in 2 cases, was weak and patchy in 1 case, and was negative in 1 case. Two (50%) of 4 tumors showed deletion of RB1 by fluorescence in situ hybridization. Loss of Rb staining was seen in 1 tumor with RB1 deletion by fluorescence in situ hybridization, whereas intact Rb staining was observed in 1 nondeleted case studied. In conclusion, this rare variant of myofibroblastoma is a distinct subgroup of tumors among an already uncommon category of (smooth muscle) breast tumors. Some reported examples of "parenchymal leiomyoma" may represent the leiomyomatous variant of myofibroblastoma.

Aggressive extracutaneous B-cell lymphomas span the various stages of B-cell ontogeny and include B-cell lymphoblastic lymphoma, Burkitt lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma. Diffuse large B-cell lymphomas represent the most common histologic subtype of non-Hodgkin lymphomas, comprising 30% of adult non-Hodgkin lymphomas in the United States. A distinctive form of diffuse large B-cell lymphoma is the double-hit lymphoma, with most cases exhibiting a combined MYC and BCL2 rearrangement, leading some hematopathologists to propose the term MYC/BCL2 lymphoma. More recently, MYC rearrangement with multiple copies/gain of BCL2 or multiple copies/gain of MYC with a BCL2 rearrangement have been described and exhibit a very similar clinical course to conventional double-hit lymphomas. We report the seventh case of diffuse large B-cell lymphoma exhibiting this distinct cytogenetic abnormality and the first reported case in the skin. The patient's clinical course was aggressive, succumbing to disease 18 months after his initial presentation.

OBJECTIVES/OBJECTIVE:Cytogenetic studies on cutaneous lymphomas are rare, and very little is known about their prognostic value. We present a rare case of primary cutaneous follicle center lymphoma (PCFCL) with a complex translocation presenting with cutaneous and extracutaneous dissemination in the lymph node. METHODS:Morphologic, immunohistochemical, conventional cytogenetic, and fluorescence in situ hybridization (FISH) studies were performed on this patient. RESULTS:A combination of cytogenetic and FISH analysis identified a complex novel four-way t(2;14;9;3) (p11.2;q32;p13;q27) translocation involving rearrangements of BCL6, immunoglobulin light and heavy chain genes, and an unknown gene on 9p. CONCLUSIONS:Our report elaborates the morphologic and immunohistochemical features in combination with cytogenetic and molecular cytogenetic analysis of PCFCL, which provide additional insight into the clinical and biologic behavior of this lesion.

The BCR-PDGFRA fusion is a very rare event. To date, only eight cases of hematolymphoid neoplasms with the BCR-PDGFRA fusion gene have been reported. All cases except one had eosinophilia. We present the first case of T acute lymphoblastic leukemia with a t(4;22)(q12;q11.2) involving the BCR and PDGFRA genes, without associated eosinophilia. Radiology showed splenomegaly and extensive lymph node involvement. The patient rapidly achieved complete remission with treatment protocol for Philadelphia chromosome-negative acute lymphoblastic leukemia.