Immunohistochemistry is a technique that uses antigen-antibody interactions to detect specific proteins in cells. This technique has several essential applications in lymphoma diagnosis, including identifying the cell lineage and phase of maturation, detecting specific genetic alterations, visualizing the degree of cell proliferation, and identifying therapeutic targets. CD3 is a pan T-cell marker expressed on most of the mature T/NK-cell lymphomas, except for anaplastic large cell lymphoma, whereas CD20 is a pan B-cell marker that is expressed on most of the mature B-cell lymphomas. CD79a may be a good alternative to CD20, compensating for its loss owing to the plasmocytic differentiation of tumor cells or history of rituximab administration. CD56, a neuroendocrine marker, is used as an NK cell marker in lymphoma diagnosis. Characteristic translocations occurring in follicular lymphoma (BCL2) and mantle cell lymphoma (CCND1) can be detected by the overexpression of Bcl-2 and cyclin D-1 in immunohistochemistry, respectively.Ki-67 reflects the degree of tumor cell proliferation by indicating cells in cell cycle phases other than G0. With the development of immunotherapy, several antibodies against markers such as programmed death-ligand 1 (PD-L1), CD19, and CD30 have been used as biomarkers to identify therapeutic targets. It is critical to properly fix the specimens to obtain accurate immunohistochemical results. Therefore, all processes, from tissue collection to the final pathological diagnosis, must be performed appropriately for accurate lymphoma diagnosis.

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma (GC), as defined by the novel classification recently proposed by The Cancer Genome Atlas. EBVaGC has several clinicopathological features such as longer survival and higher frequency of lymphoepithelioma-like carcinoma (LELC) and carcinoma with Crohn's disease-like lymphoid reaction that distinguish it from EBV-negative GC. The intensity and pattern of host cellular immune response in GC have been found to significantly correlate with the prognosis of patients with GC, suggesting that immune reaction and tumor microenvironment have critical roles in the progression of GC, and in particular, EBVaGC. Here, we reviewed the cellular and molecular mechanisms underlying prominent immune reactions in patients with EBVaGC. In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra- or peritumoral immune cell infiltration. The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial. Overall, the underlying mechanisms and clinical significance of the host cellular immune response in patients with EBVaGC have not been thoroughly elucidated. Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.
Classification ; Genome ; Herpesvirus 4, Human ; Humans ; Immunity, Cellular ; Prognosis ; Stomach Neoplasms ; Tumor Microenvironment

Congenital peribronchial myofibroblastic tumor (CPMT) is a benign pulmonary spindle cell neoplasm of intrauterine and perinatal period, which is thought to arise from primitive peribronchial mesenchyme. We present a case detected incidentally in a one-month-old infant. The solid and partially necrotic tumor involved the right middle and lower lobes of the lung with extension to the diaphragm. Histologically, the tumor was composed of fasciculated monotonous spindle cells, proliferating peribronchiolar cartilage and round cells with rich vasculature, and high mitotic activity was identified in the round cell area. Immunohistochemical and electron microscopic studies showed that the spindle cells were myofibroblastic in phenotype. Although the tumor showed several malignant pathological features, recurrence was not observed in the two-year follow-up period, consistent with the benign clinical behavior of CPMT.
Cartilage ; Diaphragm ; Electrons ; Follow-Up Studies ; Humans ; Infant ; Lung ; Mesoderm ; Myofibroblasts ; Phenotype ; Recurrence

Background: The implication of the presence of tumor-infiltrating T lymphocytes (TIL-T) in diffuse large B-cell lymphoma (DLBCL) is yet to be elucidated. We aimed to investigate the effect of TIL-T levels on the prognosis of patients with DLBCL. Methods: Ninety-six patients with DLBCL were enrolled in the study. The TIL-T ratio was measured using QuPath, a digital pathology software package. The TIL-T ratio was investigated in three foci (highest, intermediate, and lowest) for each case, resulting in TIL-T–Max, TIL-T–Intermediate, and TIL-T–Min. The relationship between the TIL-T ratios and prognosis was investigated. Results: When 19% was used as the cutoff value for TIL-T–Max, 72 (75.0%) and 24 (25.0%) patients had high and low TIL-T–Max, respectively. A high TIL-T–Max was significantly associated with lower serum lactate dehydrogenase levels (p < .001), with patient group who achieved complete remission after RCHOP therapy (p < .001), and a low-risk revised International Prognostic Index score (p < .001). Univariate analysis showed that patients with a low TIL-T–Max had a significantly worse prognosis in overall survival compared to those with a high TIL-T–Max (p < .001); this difference remained significant in a multivariate analysis with Cox proportional hazards (hazard ratio, 7.55; 95% confidence interval, 2.54 to 22.42; p < .001). Conclusions Patients with DLBCL with a high TIL-T–Max showed significantly better prognosis than those with a low TIL-T–Max, and the TIL-T–Max was an independent indicator of overall survival. These results suggest that evaluating TIL-T ratios using a digital pathology system is useful in predicting the prognosis of patients with DLBCL.

BACKGROUND: The amplification of murine double minutes (MDM2) is the primary feature of well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS), while DDIT3 rearrangement is the main one of myxoid liposarcomas (MLPS). Our aim was to evaluate the added value of MDM2 amplification and DDIT3 rearrangement in making a diagnosis and classifying lipogenic tumors. METHODS: Eighty-two cases of liposarcoma and 60 lipomas diagnosed between 1995 and 2010 were analysed for MDM2 amplification and DDIT3 rearrangement using a fluorescence in situ hybridization (FISH). The subtypes of liposarcoma were reclassified according to the molecular results, whose results were reviewed with an analysis of the relevant histologic and immunohistochemical findings. RESULTS: One case of lipoma (1.67%) was reclassified as a WDLPS. Of the liposarcomas, 13.4% (16/82) were reclassified after the molecular testing. Five cases of MLPS were reclassified as four cases of DDLPS and one case of myxoid lipoma. Two cases of WDLPS were reclassified as one case of spindle cell lipoma and another case of myxofibrosarcoma. Four cases of DDLPS were reclassified as two cases of leiomyosarcoma, one case of angiomyolipoma and another case of fibroinflammatory lesion. Of the six cases of pleomorphic liposarcoma, five were reclassified as DDLPS. CONCLUSIONS: In our series, a critical revision of diagnosis was found at a rate of 3.5% (5/142) after a review of the lipomatous lesions. The uses of molecular testing by MDM2 and DDIT3 FISH were valuable to make an accurate subtyping of liposarcomas as well as to differentiate WDLPS from benign lipomatous tumor.
Angiomyolipoma ; Fluorescence ; In Situ Hybridization ; In Situ Hybridization, Fluorescence ; Leiomyosarcoma ; Lipoma ; Liposarcoma ; Liposarcoma, Myxoid

Primary acinic cell carcinoma (ACC) of the lung is very rare and this tumor is thought to arise from pluripotent cells of the submucosal glands of the tracheobronchial tree. We report here on a case of primary ACC of the lung in a 68-year-old man who had a solitary pulmonary nodule in the left lower lobe. The patient was symptomless and the lesion was found on a chest X-ray taken during a regular health checkup. The video assisted thoracoscopic surgery wedge resection revealed an ovoid yellow tan solid mass that was 1.8 cm at the largest diameter. Microscopically, the neoplastic cells grew in solid sheets of round cells with eccentric nuclei and abundant basophilic granular cytoplasm. There were no mitotic figures or areas of pleomorphic or anaplastic cells. Immunohistochemical staining for cytokeratin (AE1/AE3) was positive, but the staining for chromogranin A and CD56 was negative. Ultrastructural examination revealed polyhedral cells with many zymogen granules of varying electron density. The patient is well 4 months postoperatively.
Acinar Cells ; Aged ; Basophils ; Carcinoma, Acinar Cell ; Chromogranin A ; Cytoplasm ; Electrons ; Humans ; Keratins ; Lung ; Lung Neoplasms ; Secretory Vesicles ; Solitary Pulmonary Nodule ; Thoracic Surgery, Video-Assisted ; Thorax ; Triacetoneamine-N-Oxyl

Erdheim-Chester disease (ECD), also known as non-Langerhans cell histiocytosis, is a multi-systemic disease with unclear pathogenesis. Based on a small number of case studies, pegylated interferon-α (PEG-IFN-α) has been used as the front-line treatment option. However, there are limited data regarding administration of ropegylated-interferon α-2b (ROPEG-IFN-α 2b) for ECD patients. Herein, we report two cases of severe ECD treated with two types of PEG-IFN-α. One patient with heart and skeleton involvement and BRAF V600E mutation was treated with weekly PEG-IFN-α 2a. Another patient with bone involvement and no BRAF V600E mutation was administered monthly ROPEG-IFN-α 2b. The two types of PEG-IFN-α showed excellent disease control, excellent survival outcomes, and manageable toxicities in ECD patients. These results suggest that ROPEG-IFN-α 2b could be used equivalently to PEG-IFN-α 2a for management of advanced ECD.

BACKGROUND: The p16INK4a gene methylation has been reported to be a major tumorigenic mechanism. METHODS: We evaluated the methylation status of the p16INK4a genes in 231 invasive breast cancer and 90 intraductal carcinoma specimens using a methylation-specific polymerase chain reaction and p16 protein expression using immunohistochemistry. The quantity of cell-free methylated p16INK4a DNA in the plasma samples of 200 patients with invasive breast cancer was also examined using a fluorescence-based real-time polymerase chain reaction assay. RESULTS: The frequencies of p16INK4a methylation in invasive and intraductal tumors were 52.8% (122/231) and 57.8% (52/90), respectively. The p16 protein was overexpressed in 145 of the 231 invasive carcinomas (62.8%) and 63 of the 90 intraductal carcinomas (70%). High p16 expression in invasive carcinomas correlated significantly with a high histologic grade, a negative estrogen receptor and progesterone receptor status, p53 immunoreactivity and high Ki-67 expression with immunohistochemistry. In addition, the methylation index of p16INK4a was significantly higher in the cancer patients than the normal controls (p<0.001). CONCLUSIONS: High p16 immunoreactivity correlated with a loss of differentiation in breast carcinomas and high frequency of p16INK4a promoter methylation in both invasive and intraductal carcinomas, suggesting it may be involved in the pathogenesis of breast cancer.
Breast ; Breast Neoplasms ; Carcinoma, Intraductal, Noninfiltrating ; DNA ; Estrogens ; Genes, p16 ; Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Methylation ; Plasma ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; Receptors, Progesterone

Malakoplakia is a characteristic inflammatory condition, which is usually seen in the urogenital tract, and less frequently in the gastrointestinal tract. We present a case of colonic malakoplakia in an immunocompromised patient. A 55-year-old female visited the outpatient clinic for routine cancer surveillance. Her past medical history was significant for kidney transplantation 11 years ago, and she had been taking immunosuppressants. A colonoscopy revealed several depressed flat lesions and elevated polyps, which were 0.3 to 0.4 cm in size and accompanied by whitish exudates. A biopsy revealed an infiltration of histiocytes with ample granular eosinophilic cytoplasm, with some lymphocytes and plasma cells. Many histiocytes had the characteristic morphology, described as Michaelis-Gutmann bodies: one or several round basophilic structures of approximately 1 to 10 microm in size with some being laminated, some appearing homogeneous, and others having a dense central core with a targetoid appearance. These Michaelis-Gutmann bodies were positively stained on von Kossa stain, and were diagnostic for malakoplakia.
Ambulatory Care Facilities ; Basophils ; Biopsy ; Colon ; Colonoscopy ; Cytoplasm ; Eosinophils ; Exudates and Transudates ; Female ; Gastrointestinal Tract ; Histiocytes ; Humans ; Immunocompromised Host ; Immunosuppressive Agents ; Kidney ; Kidney Transplantation ; Lymphocytes ; Malacoplakia ; Plasma Cells ; Polyps ; Transplants

Progressive multifocal leukoencephalopathy (PML) is a rare and fatal disease caused by JC virus. We report a case of PML which developed in a 61-year-old female patient with myasthenia gravis (MG) and thymoma. After 6 years of immunotherapy and chemotherapy she presented with hand weakness followed by progressive decline of consciousness. Serial brain MRI showed rapidly progressive multifocal white matter changes. The JC virus DNA was detected on cerebrospinal fluid. This is a third report of PML in MG.
Brain ; Consciousness ; DNA ; Female ; Hand ; Humans ; Immunotherapy ; JC Virus ; Leukoencephalopathy, Progressive Multifocal ; Middle Aged ; Myasthenia Gravis ; Thymoma