Owing to the rarity of deciduoid mesotheliomas, few studies have reported detailed morphological analyses. Here, we report a case of deciduoid mesothelioma along with cytological, histological, immunohistochemical, fluorescent in situ hybridization (FISH), and electron microscopic findings. The patient was a 75-year-old man with a history of asbestos exposure. Computed tomography revealed multiple nodular shadows in the left pleura, and pleural effusion. Pleural effusion cytology revealed large epithelioid tumor cells with high nuclear atypia, suggesting epithelioid mesothelioma. A biopsy revealed that the tumor tissue consisted of sheets of highly atypical, large epithelioid cells of various sizes. Immunostaining revealed that the tumor cells were positive for mesothelial cell markers, including calretinin, Wilms tumor 1, and podoplanin, and showed loss of expression of BRCA1-associated protein 1, methylthioadenosine phosphorylase, and merlin/neurofibromatosis 2. Furthermore, cyclin-dependent kinase inhibitor 2A-FISH revealed a high frequency of homozygous deletions. Based on these findings, the tumor was diagnosed as a deciduoid mesothelioma. Reflecting the histological features, electron microscopy revealed that the tumor exhibited sheets of large epithelioid cells containing round nuclei with single or multiple distinct nucleoli, and intracytoplasmic intermediate filaments; however, microvillous structures were not evident. After the diagnosis was confirmed, the patient was treated with a combination of immune checkpoint inhibitors and chemotherapy. Long-term follow-up is required, although no disease progression was observed seven months after the initiation of therapy.

We report a rare case of thymoma with extensive clear cell components, and discuss the histogenesis of clear cell transformation. Although thymic clear cell carcinoma is classified as a subtype of thymic carcinoma, thymoma with extensive clear cell components has not been recognized as a subtype in the World Health Organization classification (2021). Therefore, such thymomas may be erroneously misdiagnosed as clear cell carcinoma. Thymic clear cell carcinomas are positive for glycogen, with a high Ki67 index, whereas the clear cell component of the present tumor was negative, with a low index; this difference may help to distinguish thymomas with extensive clear cell components from thymic clear cell carcinomas. In this tumor, spindle cells predominantly proliferated in the center, whereas clear cells were densely distributed in the periphery. Hence, the initial tumor likely consisted of spindle cells, some of which transformed into clear cells as the tumor grew larger. In addition, nuclei of the clear cells were occasionally positive for autophagy-related 4 cysteine peptidase. Electron microscopically, clear cells with eccentrically located nuclei and cytoplasm contained large vacuoles, in which irregularly shaped membranous structures were observed. The histology, immunohistochemistry, and ultrastructure suggest that clear cell transformation represents a type of cellular degeneration.

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. 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. 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.

Both combined hepatocellular-cholangiocarcinoma (cHCCCCA) 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.

Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a rare tumor that typically affects women with Hashimoto’s thyroiditis. The present case was a man in his late 50s who was diagnosed with Graves’ disease at the age of 10 and was given antithyroid hormone for five years. The computed tomography scan revealed a nodular lesion in the right lobe, and the lesion was cytologically suspected as papillary carcinoma. No lymph node metastases or distant metastases were found. Before total thyroidectomy, high serum anti-thyroid peroxidase (TPO) and antithyroglobulin (TG) antibody titers, with no eosinophilia were detected. In a few small areas of the tumor center, small tumor cell foci with mild to moderate atypia, displaying mucous glandular cell and squamous cell differentiation, were found. The tumor was completely replaced by prominent sclerosing fibrosis, which was accompanied by tumor cell infiltration. The tumor had invaded the adjacent parenchyma and perithyroidal fatty tissue. In addition to lymphocytes and plasma cells, a large number of eosinophils were observed within the tumor. Immunohistochemically, tumor cells were strongly positive for p63, 34βE12, and TTF-1, but weakly for PAX8. Using fluorescence in situ hybridization (FISH), no MAML2 translocation was detected. Taken together with these findings, the present tumor was diagnosed as primary thyroid sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE). This case is the first to report thyroid SMECE associated with Graves’ disease. IL-5 immunostaining was performed to identify eosinophilia within the present tumor. As a result, the tumor cells were found to be positive for IL-5. The present tumor is also the first to indicate IL-5 production of SMECE.

Salivary gland neoplasms are uncommon, and their epidemiology in Japan has not been well described. We conducted a retrospective review of salivary gland tumors registered in the Hiroshima Tumor Tissue Registry over a period of 39 years. The subjects were 5015 cases ranging in age from 6 to 97 (mean, 54.3) years old. The incidence of both benign tumors and malignant tumors increased with age until 60–69 years and then declined. Among the 5015 salivary gland neoplasms, 3998 (80%) were benign and 1017 (20%) were malignant. Pleomorphic adenoma (PA) was the most frequent benign tumor (68%), followed by Warthin tumor (26%). Adenoid cystic carcinoma (ACC) (27%) and mucoepidermoid carcinoma (MEC) (26%) were the two most frequent malignant tumors. Characteristically, there was a very low incidence of polymorphous adenocarcinoma in Japan. The average annual age-adjusted incidence rate per 100,000 population was 3.3 for benign tumors and 0.8 for malignant tumors. This is the large-scale multi-institutional analysis to describe the characteristics of salivary gland neoplasms, based on the pathological tissue registry data. We hope that the present data can contribute to early diagnosis and effective treatment of salivary gland tumors and to cancer prevention.

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.

背景 : ラブドイド細胞の出現を伴う甲状腺未分化癌はきわめてまれである. 今回, 最近経験した 1 例の穿刺吸引細胞診所見, 転写法による免疫細胞化学的所見, 腫瘍の組織学的および電顕所見について報告する.

症例は53歳の男性で，主訴は黄疸であった．腹部CTで肝内肝外胆管・主膵管の拡張，十二指腸乳頭部腫瘤を認めた．術前の生検では腺癌が疑われ，亜全胃温存膵頭十二指腸切除術を施行した．病理組織は上皮様細胞が充実性，索状に増殖し，腺管構造は認めず，免疫染色検査ではCD56（+），chromogranin A（−），synaptophysin（−）であった．腺癌や内分泌細胞癌は否定的で，未分化癌と診断した．最終診断は十二指腸乳頭部未分化癌，露出腫瘤型，15 mm，pT3a，pN0，pM0，pStage IIAであった．術後はS-1で補助化学療法を開始したが，肝転移・リンパ節転移を認め，gemcitabineとS-1併用療法に変更した．十二指腸乳頭部未分化癌は非常にまれで悪性度が高く予後不良である．予後改善には術後補助化学療法が有効とされるが，一定の見解はなく今後のさらなる検討が望まれる．

症例は63歳の男性．2カ月前から出現した左頸部リンパ節腫脹のため他院で頸部リンパ節生検を行ったが診断できず，確定診断および治療目的で他院より紹介となった．CT・PET検査では，甲状腺左葉の5cm大の腫瘤と左頸部から上縦隔にかけての複数のリンパ節腫大のみを認めた．甲状腺左葉腫瘤の穿刺細胞診は鑑別困難であった．低悪性度甲状腺悪性リンパ腫および左頸部～上縦隔リンパ節浸潤との術前診断で，確定診断と一期的な治療を兼ねて甲状腺全摘およびリンパ節郭清を施行した．リンパ節浸潤を伴うgrade1相当のBCL2陰性限局期甲状腺濾胞性リンパ腫と診断され，追加治療は行うことなく良好な経過が得られている．予後の良いBCL2陰性限局期甲状腺濾胞性リンパ腫では，甲状腺全摘術単独治療も治療選択肢の一つになる可能性があると考えられた．

症例は73歳，男性．5年前に2cmであった甲状腺右葉腫瘤が4cmに増大し，自覚症状もあって当院を再受診．甲状腺超音波検査では境界明瞭で内部エコーレベルは低く均質な腫瘤であり，穿刺細胞診によって鑑別困難と診断された．CT検査では周囲臓器浸潤，リンパ節腫大，肺肝骨への遠隔転移や他臓器の腫瘤性病変も認めなかった．悪性腫瘍診断で甲状腺全摘術+D2aを行った．病理組織学的所見より，筋膜炎様の間質を伴う甲状腺乳頭癌，T4a，N1a，M0，Ex2（気管），Stage IVAと診断した．術後1年4カ月で，頸部局所再発，左前頭葉孤立性脳転移，多発骨転移・多発肺転移・多発肝転移をきたし，病状の急速な悪化で永眠された．PTC-FSは急速に予後不良な経過を辿る可能性があると考えられ，診断後迅速に治療を行うことが肝要である．

症例は73歳の女性で，腹痛・嘔吐を主訴に2012年9月当院を受診した．膵酵素の上昇，膵尾部の腫大・毛羽立ち像とその中枢側に14 mm大の腫瘤を認め，腫瘍随伴性急性膵炎と診断した．擦過細胞診で低分化腺癌を認め，膵体尾部切除を施行した．出血を伴う充実性腫瘍で，膵管癌の成分とともに反応性の多核巨細胞を交えた膵退形成癌（破骨細胞様巨細胞型）であった．2014年5月，残膵に占居性病変が出現したものの，再発の診断には至らず，慎重に観察していた．2014年11月，膵酵素の上昇を伴う腹痛を自覚した．残膵の腫瘤は増大，擦過細胞診で多核化した腫瘍細胞を認めた．残膵再発と診断し，2014年12月，残膵全摘を施行した．病理組織学的にも退形成癌の再発であることが示された．急性膵炎をじゃっ起する膵癌は多くはない．さらに，退形成癌は比較的まれで，かつ予後不良とされており，初回手術後に再発巣の再切除が可能であった例は極めてまれである．

目的 : 体腔液中に出現する collagenous stroma を伴う反応性中皮細胞集塊 (以下 : CS 集塊) の臨床細胞学的特徴を明らかにする. 方法 : 対象は 288 例 (胸水 200 例, 腹水 88 例) である. CS 集塊の出現頻度とパパニコロウ染色標本 1 枚当たりの個数を, 悪性細胞が認められた「細胞診陽性群」と, 認められなかった「細胞診陰性群」の 2 群に分類し, 両者を比較検討した. さらに, CS 集塊を構成する反応性中皮の数, CS 集塊の層数, collagenous stroma (以下 : CS) の大きさなどの形態学的所見について検討した. 成績 : CS 集塊の出現頻度は, 「細胞診陽性群」が 91 例中 19 例 (20.9%) にみられ, 「細胞診陰性群」は 197 例中 7 例 (3.6%) であり, 前者が有意に高かった (p<0.001). CS 集塊の出現個数は, 「細胞診陽性群」が平均 17.9 個で「細胞診陰性群」の平均 5.0 個よりも有意に多かった (p=0.012). CS 集塊の層数は 1 層と 2 層が, CS 集塊を構成する細胞の数は 19 個以下が多くみられ, CS は大小不同を呈した. 結論 : CS 集塊は, 小型で平面的な出現様式を示し, 癌性腔水症でみられる反応性中皮の形態学的特徴の一つと考えられた.

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.

症例は77歳の女性で，血便を主訴に近医を受診した．精査にて直腸癌を指摘され，2014年8月に直腸癌に対して手術施行された．この術前より肝腫瘤を指摘されていたため，切除目的に当科紹介となった．腹部造影CTでは肝臓S8にring enhancementを伴う11 mm大の結節影を認めた．Ethoxybenzyl-MRI（EOB-MRI）ではT1 強調像で低信号，T2強調像で高信号，拡散の低下を認め，肝細胞相で低信号を呈した．同病変はFDG-PETにても集積の亢進を認めたため，転移性肝癌に矛盾しない所見であり，術前診断は直腸癌同時性肝転移とした．手術はS8の肝部分切除術を施行した．病理組織学的検査ではreactive lymphoid hyperplasia（以下，RLHと略記）とされた．肝臓に発生したまれなRLHを経験したため，報告する．

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.

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.

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.

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.