Does maternal separation accelerate maturation of perineuronal nets and parvalbumin-containing inhibitory interneurons in male and female rats?

Early life adversity impacts on a range of emotional, cognitive, and psychological processes. A recent theoretical model suggests that at least some of these effects are due to accelerated maturation of specific physiological systems and/or neural circuits. For example, maternal separation (MS), a model of early life adversity in rodents, accelerates maturation of memory systems, and here we examined its impact on maturation of perineuronal nets (PNNs) and parvalbumin (PV)-containing inhibitory interneurons. PNNs are specialized extracellular matrix structures suggested to be involved in stabilizing long-term memories and in the closure of a sensitive period in memory development. PV-containing inhibitory interneurons are the type of cell that PNNs preferentially surround, and are also thought to be involved in memory. In Experiment 1, with male rats, there was an increase in PNNs in both the amygdala and prefrontal cortex with age from infancy to juvenility. Contrary to prediction, MS had no impact on either PNN or PV expression. The same pattern was observed in female rats in Experiment 2. Taken together, these data show that the early maturation of memory in MS infants is not due to an accelerated maturation of PNNs or PV-containing cells in either the amygdala or prefrontal cortex.

Clinical prognostic factors and outcomes of essential thrombocythemia when transformed to myelodysplastic syndromes and acute myeloid leukemia.

Transformation of essential thrombocythemia (ET) to myelodysplastic syndromes or acute myeloid leukemia is infrequent, comprising 1-5% of cases with dismal clinical outcome. Studies on prognosis in ET patients with leukemic transformation are limited. The large cohort included 40 patients (1990-2014) with ET transformation (median age of 59 years, M:F of 1:1). Median time from ET diagnosis to transformation was 76 months (26-481) with median follow-up time of 15 years. Advanced age, myelofibrosis (grade 2-3), and leukocytosis at the time of transformation were associated with inferior OS from transformation (p<0.05). Given rarity of the clinical scenario, multicenter efforts are encouraged.

Follicular lymphoma with progression to diffuse large B-cell lymphoma and concurrent CD5-negative mantle cell lymphoma-3 entities in a lymph node.

A 68-year-old woman with a history of follicular lymphoma had pathological findings of grade 3B follicular lymphoma, mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL) identified in 1 lymph node. The DLBCL appeared to be a transformation of the follicular lymphoma. The nodules were diffusely and strongly positive for CD20, BCL6, and BCL2. CD43 highlighted smaller lymphocytes in a fraction of the nodules. BCL1 staining was variable with a mixture of nodular and mantle zone patterns. The diffuse areas showed weaker positivity for CD10, BCL2, and BCL6. CD3 and CD5 highlighted intermixed T cells. The Ki-67 proliferative index was overall estimated to be 60%. Fluorescent in situ hybridization performed on the lymph node was positive for CCND1/IGH. The patterns of BCL1 and BCL6 staining demonstrated 2 separate populations of neoplastic B lymphocytes.

B-lymphoblastic leukemia/lymphoma associated with t(8;13)(p11;q12)/ ZMYM2 (ZNF198)-FGFR1 : rare case and review of the literature.

Myeloid and lymphoid neoplasms with fibroblastic growth factor receptor-1 (FGFR1) abnormalities originate from mutated pluripotent stem cells and have a heterogeneous clinical presentation. There are 12 identified partner genes commonly involved in FGFR1 translocation at an 8p11 breakpoint. In FGFR1-related neoplasms, T-lymphoblastic lymphoma with eosinophilia is the most common clinical scenario, whereas acute B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is rare. To date, only 7 cases of B-ALL/LBL with FGFR1 abnormalities have been reported. Here, we report an additional case of a 64-year-old gentleman with leukocytosis, eosinophilia and diffuse mediastinal and general lymphadenopathy. Bone marrow examination showed patchy infiltrates of immature precursors/blasts, along with myeloid/eosinophilic hyperplasia. Immunophenotyping confirmed increased B lymphoblasts (30-40%). Karyotyping revealed cytogenetic abnormalities, including t(8;13)(p11;q12)/ZMYM2 (ZNF198)-FGFR1 and trisomy 21. The patient did not respond to hyper-CVAD chemotherapy and within 4 months developed acute myelomonocytic leukemia and expired 11 months after the initial diagnosis. Similar cases from the literature are reviewed.

Malignant histiocytosis of the skin: a case report and review of the literature.

BACKGROUND: Malignant histiocytosis is a rare neoplasm composed of abnormal histiocytes typically affecting the liver, spleen, lymph nodes, and bone marrow. This entity has been rarely documented involving the skin and has never been reported confined to the skin. MAIN OBSERVATIONS: A 74-year-old white man presented to the dermatology clinic with complaints of a non-healing ulcerated lesion on his cheek of several months duration. Histopathological examination revealed a poorly circumscribed neoplasm consisting of pleomorphic epithelioid cells with abundant foamy cytoplasm. Immunohistochemistry was positive for CD-43, CD-68, and lysozyme, but negative for CD-3, CD-20, CD-30, CD-34, SMA, CD-1a or S-100. The prominent CD-68 and lysozyme staining along with the histological features, the clinical presentation of erythematous nodules with diffuse erythematous plaques, and absence of bone marrow findings, led to the diagnosis of malignant histiocytosis confined to the skin. CONCLUSION: Malignant histiocytosis involving the skin is rare. The presence of large pleomorphic epithelioid cells with foamy cytoplasm, with or without engulfed erythrocytes should alert the dermatopathologist to the possibility of malignant histiocytosis. Appropriate immunohistochemical evaluation, including CD-43, CD-68, CD-1a, S-100, and lysozyme, should be completed to confirm the diagnosis.

Acetylcholine receptor expression in Merkel cell carcinoma.

Neurocrest-derived tissues express muscarinic and nicotinic acetylcholine receptors (mAChR and nAChR respectively). These receptors are critical for migration of neurocrest-derived cells to their corresponding tissues during development. Recent reports demonstrate neurocrest-derived melanoma and numerous non-Merkel cell neuroendocrine tumors express both muscarinic and nicotinic receptors. In light of the controversy surrounding the origin and pathogenesis of Merkel cell carcinoma (MCC), we investigated the immunohistochemical expression of both mAChR and nAChR in MCC. Fifteen cases of primary non-metastatic cutaneous MCC archived at a large veterans' hospital and tertiary referral dermatopathology service were retrieved by computer-assisted search. Immunohistochemistry was utilized to evaluate the presence of M3, M5 and beta 2 nAChR expression. All the cases were confirmed prior to study by a single board certified dermatopathologist (MBM). Fifteen cases of primary cutaneous MCC were diffusely positive for M3 and M5 mAChR staining. All cases lacked immunohistochemical staining for the beta 2 nAChR. Despite the limited number of cases, MCC appears to uniformly express M3 and M5 receptors. These receptors have been linked to cell proliferation and migration which may confer a potential therapeutic target.