Background Twenty percent of patients with classical Hodgkin Lymphoma (cHL) have aggressive disease defined as relapsed or refractory disease to initial therapy. At present we cannot identify these patients pre-treatment. The microenvironment is very important in cHL since non-cancer cells constitute the majority of the cells in these tumors. Non-cancer intra-tumoral cells such as tumor-associated macrophages (TAMs) have been shown to promote tumor growth in cHL via crosstalk with the cancer cells. Metabolic heterogeneity is defined as high mitochondrial metabolism in some tumor cells and glycolysis in others. We hypothesized that there are metabolic differences between cancer cells and non-cancer tumor cells such as TAMs and tumor-infiltrating lymphocytes in cHL and that greater metabolic differences between cancer cells and TAMs are associated with poor outcomes. Methods A case-control study was conducted with 22 tissue samples of cHL at diagnosis from a single institution. The case samples were from 11 patients with aggressive cHL who had relapsed after standard treatment with adriamycin bleomycin vinblastine and dacarbazine (ABVD) or were refractory to this treatment. The control samples were from 11 patients with cHL who achieved a remission and never relapsed after ABVD. Reactive non-cancerous lymph nodes from 4 subjects served as additional controls. Samples were stained by immunohistochemistry for three metabolic markers: translocase of the outer mitochondrial membrane 20 (TOMM20), monocarboxylate transporter 1 (MCT1) and monocarboxylate transporter 4 (MCT4). TOMM20 is a marker of mitochondrial oxidative phosphorylation (OXPHOS) metabolism. Monocarboxylate transporter 1 (MCT1) is the main importer of lactate into cells and is a marker of OXPHOS. Monocarboxylate transporter 4 (MCT4) is the main lactate exporter out of cells and is a marker of glycolysis. The immunoreactivity for TOMM20, MCT1 and MCT4 was scored based on staining intensity and percentage of positive cells, as follows: 0 for no detectable staining in > 50% of cells; 1+ for faint to moderate staining in > 50% of cells, and 2+ for high or strong staining in >50% of cells. Results TOMM20, MCT1 and MCT4 expression was significantly different in Hodgkin and Reed Sternberg (HRS) cells, which are the cancerous cells in cHL compared to tumor associated macrophages (TAMs) and tumor-associated lymphocytes. HRS have high expression of TOMM20 and MCT1 while TAMs have absent expression of TOMM20 and MCT1 in all but 2 cases. Tumor-infiltrating lymphocytes have low TOMM20 expression and absent MCT1 expression. Conversely, high MCT4 expression was found in TAMs, but absent in HRS cells in all but 1 case. Tumor-infiltrating lymphocytes had absent MCT4 expression. Reactive lymph nodes in contrast to cHL tumors had low TOMM20, MCT1and MCT4 expression in lymphocytes and macrophages. High TOMM20 and MCT1 expression in cancer cells with high MCT4 expression in TAMs is a signature of high metabolic heterogeneity between cancer cells and the tumor microenviro...

Automated hematology analyzers generate accurate complete blood counts (CBC) results on nearly all specimens. However, every laboratory encounters, at times, some specimens that yield no or inaccurate result(s) for one or more CBC parameters even when the analyzer is functioning properly and the manufacturer’s instructions are followed to the letter. Inaccurate results, which may adversely affect patient care, are clinically unreliable and require the attention of laboratory professionals. Laboratory professionals must recognize unreliable results, determine the possible cause(s), and be acquainted with the ways to obtain reliable results on such specimens. We present a concise overview of the known causes of unreliable automated CBC results, ways to recognize them, and means commonly utilized to obtain reliable results. Some examples of unreliable automated CBC results are also illustrated. Pertinent analyzer-specific information can be found in the manufacturers’ operating manuals.

Metabolic heterogeneity between neoplastic cells and surrounding stroma has been described in several epithelial malignancies; however, the metabolic phenotypes of neoplastic lymphocytes and neighboring stroma in diffuse large B-cell lymphoma (DLBCL) is unknown. We investigated the metabolic phenotypes of human DLBCL tumors by using immunohistochemical markers of glycolytic and mitochondrial oxidative phosphorylation (OXPHOS) metabolism. The lactate importer MCT4 is a marker of glycolysis, whereas the lactate importer MCT1 and TOMM20 are markers of OXPHOS metabolism. Staining patterns were assessed in 33 DLBCL samples as well as 18 control samples (non-neoplastic lymph nodes). TOMM20 and MCT1 were highly expressed in neoplastic lymphocytes, indicating an OXPHOS phenotype, whereas non-neoplastic lymphocytes in the control samples did not express these markers. Stromal cells in DLBCL samples strongly expressed MCT4, displaying a glycolytic phenotype, a feature not seen in stromal elements of non-neoplastic lymphatic tissue. Furthermore, the differential expression of lactate exporters (MCT4) on tumor associated stroma and lactate importers (MCT1) on neoplastic lymphocytes support the hypothesis that neoplastic cells are metabolically linked to the stroma likely via mutually beneficial reprogramming. MCT4 is a marker of tumor-associated stroma in neoplastic tissue. Our findings suggest that disruption of neoplastic-stromal cell metabolic heterogeneity including MCT1 and MCT4 blockade should b studied to determine if it could represent a novel treatment target in DLBCL.

Non-Hodgkin lymphoma may occasionally contain large transformed cells resembling Hodgkin and Reed-Sternberg cells (HRS cells). We report a 63-year-old man with HRS cells in a recurrent mantle cell lymphoma (MCL). The patient initially presented with orbital MCL and recurred after 8 years with widespread involvement. The HRS cells were present in the recurrent disease but not in the initial orbital lesions, suggesting a transformed event after a prolonged disease course. Morphologically, the HRS cells were single cells and small clusters among the MCL cells and were frequently accompanied by histiocytes but without eosinophils or other inflammatory cells. The HRS cells showed a phenotype of classic Hodgkin lymphoma (cHL). The HRS cells were clonally related to the MCL, which was demonstrated by the presence of identical t(11;14) that resulted in productive cyclin D1 expression in both cell types. Review of the literature identified 7 additional MCL cases that showed a spectrum of clinical and pathologic features ranging from scattered HRS cells to true composite MCL and cHL. The HRS cells were clonally related to MCL in 4 cases (including the current case) and unrelated in 2 cases. These findings suggest MCL with HRS cells is a heterogeneous group that may represent a spectrum of transformation at the various stages. Proof of clonal relationship between HRS cells and MCL is useful to distinguish these cases from true composite MCL and cHL.

Thalidomide has shown efficacy in relapsed or refractory patients of multiple myeloma (MM). We present the adverse effect profile of thalidomide in 23 relapsed or refractory MM patients treated with this drug over a period of 15 months. Constipation (100% incidence) and sedation (87%) were the most common adverse effects. Neuropathy had low incidence and was late in onset (>12 months). Tolerance developed to sedation, constipation and skin lesions. All the adverse drug reactions were tolerable and did not warrant decrease or termination of therapy, except for peripheral neuropathy. Contrary to Western reports, peripheral neuropathy in Indian patients developed at a cumulative dose of 200 g or more after 10 months or more of therapy. Therapy was discontinued in one patient due to marked elevation of liver enzyme that was later attributed to acute hepatitis C infection. Only one patient dropped out of the trial for unknown reasons. Overall, thalidomide was found to be a relatively safe drug that can be used over a prolonged period of time.

VE1 immunohistochemistry is a useful and convenient surrogate for detecting BRAF V600E mutation in BM biopsy specimens decalcified with hydrochloric or formic acid-based solutions.

IntroductionAlveolar adenomas are extremely rare, benign, primary lung tumors of unknown histogenesis that are characterized by proliferative type II alveolar epithelium and septal mesenchyma. Mostly incidental, they are clinically important as they can imitate benign primary and secondary malignant tumors and at times are difficult to differentiate from early-stage lung cancer. We describe the case of a 59-year-old man with an incidental microscopic alveolar adenoma coexisting with poorly differentiated lung carcinoma.Case presentationA 59-year-old Caucasian man with a medical history of smoking and chronic obstructive pulmonary disease was incidentally found to have a right upper lobe mass while undergoing a computed tomographic chest scan as part of a chronic obstructive pulmonary disease clinical trial. Our patient underwent a right upper lobectomy after a bronchoscopic biopsy of the mass revealed the mass to be a carcinoma. A pathological examination revealed an incidental, small, 0.2 cm, well circumscribed lesion on the staple line margin of the lobectomy in addition to the carcinoma. Histopathological and immunohistochemical examinations revealed the lesion to be an alveolar adenoma.ConclusionsWe report the rare presentation of a microscopic alveolar adenoma coexisting with lung carcinoma. Alveolar adenoma is an entirely benign incidental neoplasm that can be precisely diagnosed using immunohistochemical analysis in addition to its unique histopathological characteristics.

The sensitivity of the DM96 for detecting PLT clumps can be maximized to 82.8% by reviewing the entire white blood cell screen and the entire PLT screen. Microscopic review of the blood smears yielded a PLT-clump detection rate of 99.0% when we examined the feather edge and the readable area of the smear.