Iatrogenic immunodeficiency-associated lymphoproliferative disorders are rare. A small subset of these lesions resembles classical Hodgkin lymphoma (CHL), but there are few data in the literature about these lesions. We describe 10 patients with autoimmune diseases treated with immunomodulator therapeutic agents who developed CHL. The autoimmune diseases included rheumatoid arthritis (n=5), systemic lupus erythematosus (n=2), dermatomyositis (n=1), autoimmune hepatitis (n=1), and Crohn disease (n=1), and the immunomodulatory therapies were methotrexate, azathioprine, tumor necrosis factor-α inhibitors, and thalidomide alone or in various combinations. The study group included 9 women and 1 man with a median age of 50 years (range, 25 to 77 y). The histologic features supported CHL in all cases with Reed-Sternberg (RS) and Hodgkin (H) cells in an inflammatory cell background, although the neoplasm could only be subclassified in 3 patients: 2 nodular sclerosis and 1 mixed cellularity. Immunohistochemical analysis supported the diagnosis of CHL. In all cases the RS-H cells were CD30. Nine of 10 cases were CD15, whereas CD20 was expressed variably in 4/10 cases. CD45/LCA was negative in 8 cases assessed. In situ hybridization for Epstein-Barr virus-encoded RNA was positive in the RS-H cells in 8/10 cases. The microenvironment of these lesions depicted a predominance of T-regulatory cells and M2 histiocytes. Clinical follow-up data were available for 7 patients, with a median posttreatment period of 27 months (range, 12 mo to 7 y). In all 7 patients immunomodulatory drug therapy was discontinued, and chemotherapy for CHL was administered; 2 patients also received local radiation. All 7 patients achieved complete remission and are alive. We conclude that iatrogenic immunodeficiency-associated CHL is highly associated with Epstein-Barr virus infection, and patients usually have a good outcome after discontinuation of immunomodulatory agents and chemotherapy for CHL.

The B-Raf proto-oncogene (BRAF) encodes a cytoplasmic serine/threonine kinase with a key role in regulating the mitogen-activated protein kinase signal transduction pathway. An activating missense mutation in codon 600 of exon 15 (V600E) of BRAF gene has been identified in multiple neoplasms including melanoma, colorectal carcinoma, papillary thyroid carcinoma, hairy cell leukemia, and Langerhans cell histiocytosis. Patients with BRAF V600E-mutated melanoma respond to FDA-approved BRAF inhibitors. In addition, subsets of other BRAF V600E-mutated tumors may also benefit from BRAF inhibitor therapy. Currently, clinical laboratories typically use molecular-based methods for mutation analysis. However, recently a BRAF V600E mutation-specific antibody has become available as a cost-effective alternative method to DNA-based molecular testing. We analyzed multiple tumor types including melanoma, colorectal carcinoma, papillary thyroid cancer, hairy cell leukemia, and Langerhans cell histiocytosis using both DNA-based sequencing and the BRAF V600E mutation-specific antibody. Our results show a high degree of concordance between the 2 methods. However, the high concordance seems to be limited only to the V600E mutation since variant V600 mutations are missed by V600E mutation-specific immunohistochemistry.

Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines and produces H2O2. It facilitates the progression of gliomas and prostate cancer, but its expression and functional relevance have not been studied in lymphoma. Here, we evaluated MAOA in 427 cases of Hodgkin and non-Hodgkin lymphoma and in a spectrum of reactive lymphoid tissues by immunohistochemistry on formalin-fixed paraffin-embedded specimens. MAOA was expressed by Hodgkin Reed-Sternberg (HRS) cells in the majority of classical Hodgkin lymphomas (cHL) (181/241; 75%), with 34.8% showing strong expression. Weak MAOA was also noted in a minority of primary mediastinal large B-cell lymphomas (8/47; 17%) and in a mediastinal gray zone lymphoma. In contrast, no MAOA was found in non-neoplastic lymphoid tissues, nodular lymphocyte predominant Hodgkin lymphoma (0/8) or any other non-Hodgkin lymphomas studied (0/123). MAOA was more common in Epstein-Barr virus (EBV)-negative compared to EBV-positive cHL (P < 0.0001) and was especially prevalent in the EBV-negative nodular sclerosing subtype. Similar to primary human lymphoma specimens, most cHL-derived cell lines displayed MAOA activity, whereas non-Hodgkin-lymphoma derived cell lines did not. The MAOA inhibitor clorgyline reduced the growth of L1236 cells and U-HO1 cells, and shRNA knockdown of MAOA reduced the growth of L1236 cells. Conversely, ectopic overexpression of MAOA increased the growth of MAOA-negative HDLM2 cells. Combined treatment with clorgyline and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) was more effective in reducing cell growth than either regimen alone. In summary, MAOA is highly expressed in cHL and may reflect the distinct biology of this lymphoma. Further studies on the potential utility of MAOA as a diagnostic marker and therapeutic target are warranted.

The gene RUNX1 at chromosome 21q22 encodes the alpha subunit of Core binding factor (CBF), a heterodimeric transcription factor involved in the development of normal hematopoiesis. Translocations of RUNX1 are seen in several types of leukemia with at least 21 identified partner genes. The cryptic t(7;21)(p22;q22) rearrangement involving the USP42 gene appears to be a specific and recurrent cytogenetic abnormality. Eight of the 9 cases identified in the literature with this translocation were associated with acute myeloid leukemia (AML), with the remaining case showing refractory anemia with excess blasts, type 2. Herein, we present a patient with two preceding years of leukopenia and one year of anemia prior to the diagnosis of AML, NOS with monocytic differentiation (myelomonocytic leukemia) whose conventional cytogenetics showed an abnormal clone with 5q deletion. Interphase FISH using LSI RUNX1/RUNXT1 showed three signals for RUNX1. FISH studies on previously G-banded metaphases showed the extra RUNX1 signal on the short arm of chromosome 7. Further characterization using the subtelomeric 7p probe showed a cryptic 7;21 translocation. Our case and eight previously reported leukemic cases with the t(7;21)(p22;q22) appear to share similar features including monocytic differentiation, immunophenotypic aberrancies (often with CD56 and/or CD7), and a generally poor response to standard induction chemotherapy. About 80% of these cases had loss of 5q material as an additional abnormality at initial diagnosis or relapse. These findings suggest that t(7;21) may represent a distinct recurrent cytogenetic abnormality associated with AML. The association between the t(7;21) and 5q aberrancies appears to be non-random, however the pathogenetic connection remains unclear. Additional studies to evaluate for RUNX1 partner genes may be considered for AML patients with RUNX1 rearrangement and 5q abnormalities; however knowledge of the prognostic implications of this rearrangement is still limited.

A proportion of classical Hodgkin lymphomas harbor the Epstein Barr virus (EBV). We previously demonstrated that associations between Human Leukocyte Antigen (HLA) alleles and susceptibility to EBV+ classical Hodgkin lymphoma differ between European and Chinese populations. Data on Hispanic populations is missing. Here we examined the association between HLA type, tumor cell HLA expression and other characteristics in Hispanic Hodgkin lymphoma patients. Hispanic Hodgkin lymphoma patients diagnosed at the Los Angeles County-University of Southern California Medical Center from 2000–2012 were included (n = 65). Formalin-fixed paraffin-embedded tumor tissue was analyzed for EBV by in situ hybridization and for HLA class I and class II expression by immunohistochemistry. HLA typing was performed by HLA-A specific quantitative PCR of genomic DNA from tissue. Thirty patients (46%) had EBV+ tumors. Expression of HLA class I (p = 0.0006) was significantly associated with EBV+ tumor status in Hispanic patients, similar to Europeans and Chinese. A positive association between HLA class II expression and EBV+ tumor status, as present in large studies in Europeans, was not found (p = 0.06). The prevalences of the specific European HLA-A*01 risk and European HLA-A*02 protective types were not significantly associated with EBV+ tumors among these Hispanic patients, however numbers were too low to draw firm conclusions. The HLA-A*02:07 allele, that is associated with EBV+ Hodgkin lymphoma in Chinese, was absent. In conclusion, the association between EBV positivity in tumor cells and HLA class I expression appears to be consistent across different populations. Larger studies in Hispanics are needed to evaluate HLA allele susceptibility associations.

First identified as a distinct disease entity in HIV-positive patients, plasmablastic lymphoma is a rare aggressive disease which arises predominantly in men and is associated with immunodeficiency of all causes. Although its exact etiology is poorly understood, Epstein-Barr virus infection and MYC gene aberrations have been implicated in its development in both HIV-positive and HIV-negative patients. The disease typically involves extranodal sites with a predilection for the oral cavity but may occur in other locations. Here we present a case of plasmablastic lymphoma diffusely involving the omentum and peritoneal cavity of an immunocompetent woman, clinically mimicking an ovarian carcinomatosis. To the best of our knowledge, this is the first case in which plasmablastic lymphoma has presented as peritoneal lymphomatosis. Diagn. Cytopathol. 2017;45:243-246. © 2016 Wiley Periodicals, Inc.

Indeterminate cell histiocytosis (ICH) is an extremely rare disease and little is known about its etiology. Patients usually present with nodular, dermal proliferations of indeterminate cells, which characteristically resemble Langerhans cells but lack Birbeck granules. The clinical course is highly variable, ranging from spontaneous regression to rapid progression with reports of extracutaneous involvement, subsequent acute myeloid leukemias, and associated B-cell lymphomas. Rare cases of ICHlike reactions have been reported in the setting of scabies infestations as well as in patients who had been bitten by ticks and mosquitos. We present a successfully treated case of indeterminate cell-rich post scabietic nodules in an otherwise healthy 8-month-old boy and review the literature on similar cases. Clinical context is essential for correct interpretation of these indolent ICH-mimicking lesions, and to avert unnecessary patient anxiety and aggressive management. K E Y W O R D S histiocytosis, indeterminate cell histiocytosis, indeterminate dendritic cell tumor, postscabietic, scabies

Intravascular large B-cell lymphoma (IVLBCL) is a subtype of diffuse large B-cell lymphoma, where the neoplastic lymphoid proliferation resides predominantly within the lumens of blood vessels but with no or few circulating neoplastic cells in the peripheral circulation. Focal or subtle involvement in some cases can cause the diagnosis to be misinterpreted or even overlooked, delaying the initiation of appropriate treatment. Our report focuses on a 78-year-old woman with a progressively enlarging thyroid mass, verified by ultrasound. She underwent a hemithyroidectomy, and microscopic evaluation demonstrated nodular thyroid parenchyma with atypical large cells in an intravascular distribution pattern identified on high magnification. Thorough evaluation showed that the large intravascular cells were positive CD20, PAX-5, and Ki-67 by immunoperoxidase staining, which lead to the diagnosis of IVLBCL. This case emphasizes the subtle appearance of IVLBCL, which may be missed on low-power light microscopy, and the need for careful evaluation of thyroid resection specimens.