A Rare Case of Pleural Epithelioid Mesothelioma With a Prominent Myxoid Stroma Reported With Morphology, Fluorescent In Situ Hybridization, and Ultrastructural Findings.

Herein, we report a rare case of pleural epithelioid malignant mesothelioma with a prominent myxoid stroma. To date, detailed morphological or molecular pathological findings have not been reported for this type of tumor. Hence, we aimed to describe the cytological, histological, immuno-cytohistological, electron-microscopic, and molecular pathological findings using fluorescence in situ hybridization (FISH) in such a case. The patient was a male in his mid-sixties with a history of asbestos exposure and had originally visited the hospital with a persistent cough and fever. Chest radiography revealed left pleural effusion, and laboratory examination revealed a high titer for hyaluronic acid in the effusion. Additionally, computed tomography revealed diffuse multinodular or cystic lesions in the left parietal pleura, and pleural effusion cytology revealed large epithelioid cells with mild nuclear atypia, which were considered reactive mesothelial cells. Cytologically, Giemsa staining revealed that these cells harbored variously sized intracytoplasmic vacuoles that were Alcian-blue-positive, suggesting hyaluronan production. Biopsy revealed large epithelioid cells that loosely proliferated against a prominent myxoid background. These cells were immuno-positive for calretinin, Wilms' tumor 1, D2-40, vimentin, and cytokeratin AE1/AE3 but not for carcinoembryonic antigen, Ber-EP4, or desmin. BRCA 1 associated protein 1 immunostaining showed nuclear loss, and FISH showed homozygous deletion of cyclin-dependent kinase inhibitor 2A (p16) on chromosome 9p21. Based on these findings, the lesion was diagnosed as an epithelioid mesothelioma with a prominent myxoid stroma. Electron-microscopy demonstrated a dense microvillus pattern on the surface of the tumor cells, indicating a mesothelial cell origin, and variously sized vacuoles in the cytoplasm, confirming the presence of intracytoplasmic vacuoles demonstrated on cytology. The tumor tissues obtained during surgery harbored prominent myxoid stroma, which proved that the present tumor was consistent with this type of mesothelioma. After informed consent was obtained, the patient and family wished for total resection of the tumor and postoperative chemotherapy, and the patient eventually died eight months after surgery.

A case of dumbbell-shaped accessory scrotum with concomitant lipoma.

BACKGROUND: Accessory scrotum is a congenital scrotal anomaly that is usually located anterior to the anus and frequently presents with a lipoma in a bead-like shape. Herein, we present an unusual case of an accessory scrotum with a lipoma connected by a narrow stalk and located posterior to the anus. CASE PRESENTATION: A 1-month-old boy was referred to our hospital for a perineal mass present at birth. He was born at 37 weeks and 2 days, with a birth weight of 2962 g. No abnormalities occurred during the perinatal period, and the birth was uneventful. The mass had an unusual shape, comprising two masses connected by a narrow stalk. The base of the mass was posterior to the anus and was connected to the rectal mucosa. The proximal mass was elastic and soft without skinfolds, whereas the distal mass was elastic and soft with a scrotum-like skinfolds. Magnetic resonance imaging showed no spina bifida. High-intensity adipose tissues in both masses and low-intensity vessels or fibrous stroma in cord-like structures between the two masses were found on T2-weighted images. At 3 months of age, the patient underwent resection in the prone jackknife position. No tumorous lesions were connected to the mass on the rectal and coccyx sides, and the mass was completely removed, preserving the anal sphincter. Histologically, the distal mass had characteristics of a scrotum, whereas the proximal mass was exclusively a lipoma. The connecting stalk had normal skin structures and a blood vessel with parallel-running nerve bundles. The postoperative course was uneventful, and the patient was discharged on postoperative day 6. CONCLUSIONS: This case of accessory scrotum was unusual in its location and the presence of a stalk connecting the accessory scrotum and lipoma. The mechanism underlying accessory scrotum development remains unclear, and our report may impact the discourse regarding the embryological development of the accessory scrotum.

Synchronous Double Primary Combined Hepatocellular-cholangiocarcinoma and Cholangiolocarcinoma in a Cirrhotic Liver.

Both combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and cholangiolocarcinoma are rare primary liver cancers. cHCC-CCA is believed to originate from transformed hepatocellular carcinoma or liver stem/progenitor cells. Cholangiolocarcinoma is characterized by ductular reaction-like anastomosing cords and glands resembling cholangioles or canals containing hepatocellular carcinoma components and adenocarcinoma cells. According to the 2019 revision of the World Health Organization criteria, a subtype with stem cell features as a subclassification of cHCC-CCA was abolished for lack of conclusive evidence of the stem cell origin theory. That led to the classification of cholangiolocarcinoma with hepatocytic differentiation as cHCC-CCA. Consequently, cholangiolocarcinoma without hepatocytic differentiation is classified as a subtype of small-duct cholangiocarcinoma and is assumed to originate from the bile duct. Herein, we report the first case of double primary cHCC-CCA and cholangiolocarcinoma without hepatocytic differentiation in different hepatic segments of a cirrhotic liver. We believe this case supports the validity of the new World Health Organization criteria because the pathological finding of cHCC-CCA in this case shows the transformation of hepatocellular carcinoma to cholangiocarcinoma. Furthermore, this case may demonstrate that immature ductular cell stemness and mature hepatocyte cell stemness in hepatocarcinogenesis can coexist in the same environment. The results provide valuable insights into the mechanisms of growth, differentiation, and regulation of liver cancers.

Assessment of intrathoracic lymph nodes by FDG PET/CT in patients with asbestos-related lung cancer.

BACKGROUND: This study explored the assessment of intrathoracic lymph node metastasis by 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography computed tomography (PET/CT) in patients with asbestos-related lung cancer (ARLC). METHODS: We retrospectively reviewed the data on 35 patients with ARLC who underwent preoperative FDG-PET/CT and surgical resection between January 2012 and December 2018. We collected medical information from medical records and imaging systems and examined the FDG uptake in each lymph nodal region resected by surgery and the presence or absence of pathological lymph node metastasis. RESULTS: Pathological lymph node metastases were detected in 14 (8.70%) of 161 nodal stations. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-PET/CT were 71.4% (10/14), 87.8% (129/147), 35.7% (10/28), 97.0% (129/133), and 86.3% (139/161), respectively. Six of the eight false-positive patients had bilateral accumulations, whereas all six true-positive patients had unilateral accumulation (P=0.006). On histopathological examination, the false-positive nodes showed disruption of lymphoid follicles in the cortex, infiltration of histiocyte-like cells in the medulla, fibrous micronodules, and severe anthracosis. CONCLUSIONS: PET/CT scans of patients with ARLC showed comparable sensitivity and specificity to those of PET/CT scans of patients with conventional lung cancer reported in the literature. Many false-positive cases also showed bilateral symmetric accumulation. This method can be used to evaluate lymph node involvement in lung cancer.

O-arm Navigation-Guided Surgical Resection and Posterior Fixation for a Large Sacral Schwannoma.

Sacral schwannoma is a rare tumor with relatively few symptoms; it thus tends to be large at diagnosis and is challenging to treat surgically. We present the case of a 12-year-old girl with a large sacral schwannoma that was successfully surgically resected using O-arm navigation in a two-stage operation. First, we performed tumor resection from the posterior aspect with assisted O-arm navigation. One week later, resection from the anterior aspect was conducted with posterior spinopelvic fixation and fibula graft. We performed partial resection of the tumor from the anterior and posterior aspects as much as possible. O-arm navigation contributed to precise and safe tumor resection and implant insertion.

[Two Cases of Stage â £ Occult Breast Cancer].

The first case is a 62-year-old female who complained of painful left axillary lymph node swelling. Six months later, a CT scan revealed multiple lung nodules. Biopsies of the axillary lymph node and lung showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph node and lung. ER(+), PgR(±), HER2(1+). Letrozole was administered, and effective control was achieved for 20 months. The second case is a 62-year-old female who presented with back pain. A CT scan revealed left axillary lymph node swelling and multiple osteolytic changes in the thoracolumbar spine and rib. Biopsies of the axillary lymph node and thoracic spine showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph nodule and bone. ER(+), PgR(+), HER2(1+). Fulvestrant and denosumab were administered. However, after 6 months, she discontinued the treatment. Our results suggested that effective control could be achieved through systemic therapy and local therapy was not necessary for Stage Ⅳ occult breast cancer.

[A Case of Breast Metastasis of Gastric Cancer after an Eight Year Latency Period].

A 66-year-old woman underwent distal gastrectomy because of gastric cancer(stage ⅠB)and received no adjuvant chemotherapy. Eight years after the operation, computed tomography showed a small nodule in the right breast. Mammography did not reveal any abnormalities. Ultrasound sonography showed a diffuse and gradual non-mass-like low echoic lesion. Core needle biopsy indicated a malignancy. Partial resection of the right breast was performed to obtain a diagnosis. On postoperative histopathological examination, signet-ring cells were found in the tumor, and immunohistochemical analysis showed that both the breast tumor and the gastric carcinoma were MUC5AC-positive and MUC1-negative. We diagnosed this breast tumor as metastasis from gastric cancer. The patient has received chemotherapy with no subsequent metastatic tumors, and good control has been achieved for 21 months after the detection of the breast metastasis.

[A Case of Long-Term Survival after Para-Aortic Lymph Node Recurrence Following the Curative Resection of Gastric Cancer Treated Using Multimodality Therapy Including Salvage Surgery].

This case was observed in a man in his 70s. Although symptomatic treatment was performed for epigastralgia, endoscopic examination revealed a type 3 tumor on the fornix of the stomach to the lesser curvature of the body just above the esophagogastric junction, and the patient was diagnosed with moderately differentiated tubular adenocarcinoma(cT4bN3aM0, cStage ⅣA). As esophageal and diaphragmatic invasion was suspected based on CT findings, S-1 plus CDDP was started as preoperative chemotherapy. Although the primary lesion and lymph node metastasis decreased in size, chemotherapy was discontinued after one course due to stenosis symptoms, and total gastrectomy and D2 dissection were performed. Postoperative adjuvant chemotherapy with S-1 was started. However, 6 months after starting the treatment, para-aortic lymph node recurrence was observed, and the treatment strategy was changed to weekly PTX. After 5 courses of weekly PTX, the lymph nodes continued to increase in size, and chemotherapy was discontinued per the patient's request. The patient was followed up with CT and PET-CT; however, no new recurrent lesions were found in other sites for approximately 1 year. Therefore, para-aortic lymph node dissection was performed as the salvage surgery. Pathological findings showed that gastric cancer metastasis was present in 1 swollen lymph node only, as confirmed by PET. At present, 6 years have passed since the first operation, and there has been no recurrence. In general, para-aortic lymph node metastasis is considered to result in poor prognosis in gastric cancer. However, in the absence of other noncurative factors, a good prognosis may be obtained with combined therapeutic modalities.

Prolonged Activated Partial Thromboplastin Time and False-Positive Results for Fibrinogen and Fibrin Degradation Products in a B-Cell Lymphoma Patient.

We report a unique case of a B-cell lymphoma patient in whom IgM monoclonal gammopathy resulted in a prolonged activated partial thromboplastin time (APTT) and false-positive results for fibrinogen and fibrin degradation products (FDPs). An 86-year-old man was referred to our hospital for further examination of abnormal cells in his peripheral blood. Laboratory data upon admission revealed an elevation of monoclonal IgM, presence of FDPs and marked prolongation of APTT (>180 s). Bone marrow examination revealed a predominant involvement of B lymphoma cells. In vitro examination revealed that IgM isolated from the patient's plasma had resulted in false-positive results for FDPs and APTT. Neither hemorrhagic nor thrombotic tendency was observed in this patient, suggesting that the abnormal coagulation data were due to interference by elevated monoclonal IgM levels.

HR23b expression is a potential predictive biomarker for HDAC inhibitor treatment in mesenchymal tumours and is associated with response to vorinostat.

Histone deacetylases (HDAC) are key players in epigenetic regulation of gene expression and HDAC inhibitor (HDACi) treatment seems to be a promising anticancer therapy in many human tumours, including soft tissue sarcomas. HR23b has been shown to be a potential biomarker for sensitivity to HDACi therapy in cutaneous T-cell lymphoma and hepatocellular carcinoma. We aimed to evaluate HR23b as a candidate biomarker for HDACi response in sarcomas and gastrointestinal stromal tumours (GIST). Therefore, HR23b expression was analysed comprehensively by western blot in sarcoma and GIST cell lines covering all major clinically relevant subtypes. MTT assay and ApoTox-Glo(TM) Triplex assay were performed after treatment with vorinostat, belinostat, mocetinostat and entinostat. HR23b protein expression was measured under HDACi treatment. Furthermore, HR23b expression levels were immunohistochemically determined in a large set of 523 clinical samples from sarcoma and GIST patients. Western blot analyses showed that sarcomas differ significantly in their expression of HR23b protein. All HDACi were able to regulate proliferation and apoptosis in vitro. Sensitivity to vorinostat correlated significantly with HR23b protein expression. Immunohistochemical prevalence screening in clinical samples of relevant adult-type tumours revealed that 12.5% of sarcomas (among them malignant peripheral nerve sheath tumours, pleomorphic liposarcomas, leiomyosarcomas, dedifferentiated liposarcomas, synovial sarcomas and angiosarcomas) and 23.2% of GIST show high HR23b expression. Therefore, HDACi have antiproliferative and proapoptotic effects in sarcomas depending on the expression level of HR23b. These findings suggest that HR23b represents a candidate biomarker for HDACi sensitivity in certain sarcoma types and in GIST.

Peritoneal malignant mesothelioma (PMM), and primary peritoneal serous carcinoma (PPSC) and reactive mesothelial hyperplasia (RMH) of the peritoneum. Immunohistochemical and fluorescence in situ hybridisation (FISH) analyses.

AIMS: Peritoneal malignant mesothelioma (PMM) is an uncommon tumour, accounting for only 7-9% of all mesotheliomas in Japan. Differential diagnosis between PMM and primary peritoneal serous carcinoma (PPSC), a high-grade serous carcinoma, may be difficult, and separating reactive mesothelial hyperplasia (RMH) from PMM can be even more challenging. METHODS: To help differentiate PMM from PPSC and RMH, we used immunohistochemistry to examine mesothelial-associated markers (calretinin, AE1/AE3, CK5/6, CAM5.2, D2-40, WT-1, HBME1, thrombomodulin), adenocarcinoma-associated markers (CEA, BerEP4, MOC31, ER (estrogen receptor), PgR, TTF-1, Claudin-4, Pax8), and malignant-related and benign-related markers (epithelial membrane antigen (EMA), desmin, GLUT-1, CD146 and IMP3), and FISH to examine for homozygous deletion of 9p21. We used formalin-fixed, paraffin-embedded blocks from 22 PMMs (M:F=18:4; subtypes: 16 epithelioid, 6 biphasic), 11 PPSCs and 23 RMHs. RESULTS: Seventeen of the mesotheliomas (four PMM from women) were classified as diffuse, while five were localised. Calretinin was 91% positive in PMM, but negative in PPSC (specificity, 100%). BerEP4, Claudin-4 and PAX8 were all 100% positive in PPSC (specificities, 100%, 95% and 95%, respectively, for excluding PMM). For distinguishing PMM and RMH, sensitivity for EMA in mesothelioma was 68%, while for IMP3 and GLUT-1 it was 64% and 50%, respectively, all with high specificities. FISH analysis revealed homozygous deletion of the 9p21 locus in 11/13 PMMs, but in 0/11 RMHs. CONCLUSIONS: Calretinin and BerEP4 may be the best positive markers for differentiating PMM from PPSC. EMA, in combination with IMP3 and desmin, is useful, and homozygous deletion of 9p21 may be helpful, for differentiating PMM from RMH.

Capsule Endoscope Aspiration after Repeated Attempts for Ingesting a Patency Capsule.

Capsule endoscope aspiration into the respiratory tract is a rare complication of capsule endoscopy. Despite the potential seriousness of this complication, no accepted methods exist to accurately predict and therefore prevent it. We describe the case of an 85-year-old male who presented for evaluation of iron deficiency anemia. He complained of dysphagia while ingesting a patency capsule, with several attempts over a period of 5 min before he was successful. Five days later, he underwent capsule endoscopy, where he experienced similar symptoms in swallowing the capsule. The rest of the examination proceeded uneventfully. On reviewing the captured images, the capsule endoscope was revealed to be aspirated, remaining in the respiratory tract for approximately 220 s before images of the esophagus and stomach appeared. To our knowledge, this is the first documented case of a patient who experienced capsule endoscope aspiration after ingestion of a patency capsule. This case suggests that repeated attempts required for ingesting the patency capsule can predict capsule endoscope aspiration. We presume that paying sufficient attention to the symptoms of a patient who ingests a patency capsule could help us prevent serious complications such as aspiration of the capsule endoscope. In addition, this experience implies the potential risk for ingesting the patency capsule. We must be aware that the patency capsule could also be aspirated and there may be more unrecognized aspiration cases.

Neoadjuvant Chemotherapy with or without Concurrent Hormone Therapy in Estrogen Receptor-Positive Breast Cancer: NACED-Randomized Multicenter Phase II Trial.

Although in the neoadjuvant setting for estrogen receptor (ER)-positive breast cancers, chemotherapy or hormone therapy alone does not result in satisfactory tumor response, it is unknown whether concurrent chemo-endocrine therapy is superior to chemotherapy alone in clinical outcomes. We conducted a randomized phase II trial to test the responses of ER-positive patients to concurrent administration of chemo-endocrine therapy in the neoadjuvant setting. Women with stage II-III, ER-positive, invasive breast cancer (n=28) received paclitaxel followed by fluorouracil, epirubicin, cyclophosphamide (T-FEC) and were randomized to receive concurrent chemo-endocrine therapy consisting of goserelin administered subcutaneously for premenopausal women or an aromatase inhibitor for postmenopausal women. The primary endpoint was the pathological complete response (pCR) rate after neoadjuvant therapy. Twenty-eight patients were randomized. There were no significant differences in pCR rate between the concurrent group (12.5%;2/16) and the chemotherapy alone group (8.3%;1/12). Tumor size after therapy was significantly reduced in the concurrent therapy group (p=0.035), but not in the chemotherapy-alone group (p=0.622). Neoadjuvant chemotherapy with concurrent hormone therapy provided no significant improvement in pCR rate in ER-positive breast cancers. These preliminary results should be followed up by further studies.

Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST).

Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT.

Clinicopathologic analysis of 6 lymphomatoid gastropathy cases: expanding the disease spectrum to CD4-CD8+ cases.

Lymphomatoid gastropathy, which was first reported in 2010, is a rare NK-cell proliferation of cyCD3, CD4, CD5, CD8, CD56 phenotypes with unknown etiology. The diagnosis is challenging, as there is histopathologic similarity to malignant lymphoma. In the 2010 report on 10 cases, all lesions were located in the stomach, and all regressed without any therapy. In the present study, we analyzed 6 cases of lymphomatoid gastropathy by investigating the clinicopathologic, immunohistochemical, and molecular findings. Endoscopic and morphologic appearances of all cases were consistent with previous reports, but 2 cases showed previously unreported unique immunophenotypes of CD4CD8. Three of 6 patients underwent lower gastrointestinal examination (1 case underwent double-balloon endoscopic examination), but no patient had lesions in the lower gastrointestinal tract. No obvious difference of histology was found between the cases of CD4-CD8-typical phenotype and ones of CD4CD8 phenotype. Both cases had similar clinical behavior as the other 4 cases, implying that the spectrum of the disease is broader than initially thought. Careful clinical and endoscopic follow-up is required for the diagnosis of lymphomatoid gastropathy, and additional case studies and molecular studies are warranted to further investigate the pathophysiology of this peculiar benign mimic of lymphoma.

[HER2-Positive Advanced Gastric Cancer with Disseminated Intravascular Coagulation and Diffuse Bone Marrow Carcinomatosis Successfully Treated with S-1/Trastuzumab Chemotherapy--A Case Report].

Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor 2 (HER2), has been proven to result in a survival benefit for the treatment of patients with HER2-positive advanced gastric cancer (AGC). However, data are lacking for the treatment of those with disseminated intravascular coagulation (DIC) and diffuse bone marrow carcinomatosis. A 77-year-old woman presented with back pain and fatigue since 2 months. Esophagogastroduodenoscopy showed a scirrhous lesion in the gastric corpus, which was biopsied and identified as signet-ring cell carcinoma with HER2 overexpression on immunohistochemistry. Laboratory testing, bone scintigraphy, and bone marrow biopsy were conducted, and she was diagnosed with HER2-positive AGC with DIC and diffuse bone marrow carcinomatosis. She underwent chemotherapy with the following regimen: oral administration of 80 mg/m2 S-1 for 2 weeks and 6 mg/kg trastuzumab infusion on day 6 every 3 weeks, which significantly improved the DIC. She was discharged from the hospital 73 days after admission and survived for 438 days after diagnosis. To the best of our knowledge, this is the first case report in which HER2-positive AGC complicated by DIC with diffuse bone marrow carcinomatosis was successfully treated with combined chemotherapy consisting of S-1 plus trastuzumab.

Low-grade B-cell lymphoma presenting primarily in the bone marrow.

Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma.