The Diagnostic Utility of IDH2 R172 Immunohistochemistry in Tall Cell Carcinoma With Reversed Polarity of the Breast.

Tall cell carcinoma with reversed polarity (TCCRP) is a rare histologic type of low-grade breast cancer, consisting of tall columnar cells with reversed nuclear polarity and characterized by frequent IDH2 mutations. We herein report 3 cases of TCCRP with sequencing analyses of the IDH2 gene and immunohistochemical examination using monoclonal antibodies (11C8B1) against IDH2 R172. IDH2 R172 mutations were detected in all 3 resected tumors (R172S in 2 tumors and R172T in 1 tumor), and the presence of these mutations was confirmed by IDH2 R172 immunohistochemistry. Tumor cells of TCCRP showed strong and diffuse staining for the antibody against IDH2 R172. In 1 case, tumor tissue from 2 core needle biopsy samples collected on different days were also immunohistochemically positive for IDH2 R172. These results indicate that IDH2 R172 immunohistochemistry is suitable for the detection of TCCRP in both resection and biopsy samples. In addition, a literature review revealed that R172S and R172T account for 76% of IDH2 mutations in TCCRP, suggesting that 11C8B1, which reacts with R172S and R172T, was likely most sensitive for IDH2 -mutated TCCRP among many available antibodies for IDH2 R172. Furthermore, the combination of 2 or more antibodies against IDH2 R172 could be more effective for detecting TCCRP mutation. However, it is important to note that IDH2 R172 immunohistochemistry is not absolute, because IDH2 wild type is found in a small proportion (10%) of cases, and a few cases of IDH2 -mutated TCCRP may harbor rare subtypes of R172 that are not covered by available antibodies.

[Intravascular large B-cell lymphoma diagnosed by total hysterectomy].

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of non-Hodgkin B-cell lymphoma which occurs mainly in capillaries and small blood vessels. Successful diagnosis of IVLBCL is challenging since it lacks tumor formation and presents various clinical manifestations. An 82-year-old Asian female patient presented to our emergency department with a history of general fatigue, weight loss, and fever for two weeks. The patient's random skin biopsy was negative, and her bone marrow biopsy revealed hemophagocytic syndrome with no obvious involvement of lymphoma cells. Gallium scintigraphy showed mild uptake in the uterus, pelvis, and spine. The repetitive bone marrow biopsy result and the endometrial cytology/biopsy were negative; however, the pelvic MRI was compatible with lymphoma, revealing lesions in the corpus uteri, pelvis, and vertebral body. After laparoscopic-assisted vaginal total hysterectomy and bilateral salpingo-oophorectomy, the diagnosis of the Asian variant of IVLBCL was made. Although total hysterectomy remains controversial for elderly patients with declining performance status, we could successfully diagnose the condition and initiate the treatment. The patient's general condition improved soon after starting rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen on day 26, and she was discharged on day 45.

[A case of central nervous system primary lymphomatoid granulomatosis with multiple vascular lesions in the spinal cord and brain].

A 71-year-old man was hospitalized because of low back pain and weakness in both lower limbs. He presented with fever and stiff neck, and his cerebrospinal fluid sample contained blood. MRI revealed intramedullary and epidural hemorrhages in the spinal cord. Microhemorrhages occurred frequently in the central nervous system over a short period. A brain biopsy was performed. The diagnosis was primary lymphomatoid granulomatosis (LYG) of the central nervous system (grade 2). As a result of lymphocytic infiltration to the vascular walls in LYG, hemorrhages occurred in multiple sites in the central nervous system. The biopsy of samples from the sites of microhemorrhages proved useful for diagnosis even in the absence of mass lesions.

Is cell block technique useful to predict histological type in patients with ovarian mass and/or body cavity fluids?

The cell block (CB) technique is a generalized method utilized for the diagnostic evaluation of body cavity fluids. Ascites cytology is one of the most important diagnostic processes for epithelial ovarian cancer. However, in clinical practice, the usefulness of the CB method to diagnose this tumor remains unelucidated. Between 2008 and 2017, 15 peritoneal or pleural fluid samples obtained from patients with ovarian or peritoneal carcinoma or other gastrointestinal malignancies were preoperatively subjected to a diagnostic evaluation to predict the histological type and original organ. The CBs were made from 10% formalin neutral buffer solution fixed sediments of fluid samples after cytological smears were made by conventional method. Four-µm thickness sections were prepared from the cell blocks and stained with immunohistochemical method, using 16 kinds of antibodies and hematoxylin eosin staining method. The cellularity, architectural patterns, and morphological details were also studied. The median (range) age of patients was 73 (35-87) years. The clinical features were identified as follows: pleural effusion in 4, ovarian mass in 7, peritoneal dissemination in 12, para-aortic nodal swelling in one, and liver tumor in one (some overlapping). Five patients had a history of prior malignancy. Finally, we could accurately diagnose the histological type in 9 patients based on subsequent biopsy, surgery, and autopsy. In all 9 women, the clinical diagnosis, CB diagnosis and final pathological diagnosis were consistent. The CB technique may be a helpful modality for evaluating fluid cytology to obtain a final histopathologic diagnosis.

Molecular and immunohistologic analyses cannot reliably solve diagnostic variation of flat intraepithelial lesions of the urinary bladder.

We examined diagnostic variation of flat intraurothelial lesions with comparison with immunohistochemical and fluorescence in situ hybridization (FISH) analyses. Nine uropathologists diagnosed 23 biopsy samples from the urinary bladder. The samples were analyzed by immunohistochemical expression of cytokeratin 20, high-molecular-weight cytokeratin, Ki-67, p53, and p16(INK4a), and multicolor FISH using the UroVysion probe set (Vysis, Abbott, Des Plaines, IL). Diagnostic agreement for each classification and for nonneoplastic or neoplastic lesions was obtained in 8 (35%) and 16 (70%) of 23 lesions, respectively. The preference ratio of neoplasia to nonneoplasia (0.9 to 4.8) or carcinoma in situ to dysplasia (0.2 to 4.0) also varied among the pathologists. In 6 ancillary analyses, the majority of neoplastic lesions with diagnostic agreement indicated more than 2 aberrant results, whereas the majority of lesions without diagnostic agreement showed no or only 1 aberrant result. The molecular and immunohistochemical analyses can discriminate between neoplastic and nonneoplastic lesions; however, they cannot reliably solve diagnostic variation of flat intraepithelial lesions.

Endometrial atypical hyperplasia with clear cell change spreading throughout the endometrium.

An unusually rare case of atypical endometrial hyperplasia with clear cell change (metaplasia) spreading through almost the whole endometrium of a 37-year-old woman with infertility and abnormal bleeding is reported.

De novo cerebral aneurysms manifesting as repeated subarachnoid hemorrhage and cerebral ischemic stroke--case report.

A 29-year-old man suffered repeated subarachnoid hemorrhage and cerebral ischemic stroke over a period of 6 years. Cerebral angiography at each episode disclosed development of multiple de novo aneurysms at the bilateral middle cerebral arteries (MCAs), internal carotid arteries, right anterior cerebral artery, and right vertebral artery. Two of the ruptured aneurysms were treated by surgical and endovascular treatment, but he died of the effects of rupture of a de novo right MCA aneurysm. Histological examination at autopsy disclosed marked degenerative changes in all layers of the cerebral vessels, which were probably congenital in origin.