Akinobu Ohno

Aberrant expression of monocarboxylate transporter 4 in tumour cells predicts an unfavourable outcome in patients with hepatocellular carcinoma

The tumour cell microenvironment, which includes local oxygen saturation, pericellular pH and stromal cells, can modulate tumour progression. This study determined the prognostic impact of infiltrating tumour‐associated macrophages and the expression of monocarboxylate transporter 4 (MCT4) and glypican 3 (GPC3) in hepatocellular carcinoma (HCC) clinical specimens.

High preoperative levels of serum glypican‐3 containing N‐terminal subunit are associated with poor prognosis in patients with hepatocellular carcinoma after partial hepatectomy

Glypican‐3 (GPC3) is a glycosylphosphatidylinositol‐anchored cell surface glycoprotein overexpressed in hepatocellular carcinoma (HCC) cells and may serve as a potential molecular target for therapeutic intervention. This study evaluated the prognostic significance of serum GPC3 in HCC patients receiving curative surgery. A novel sandwich enzyme‐linked immunosorbent assay for the quantitative and sensitive determination of serum GPC3 N‐terminal subunit antigen (sGPC3N) was developed and used to measure sGPC3N levels in 25 healthy volunteers and 115 HCC patients who underwent curative partial hepatectomy. The relationships between sGPC3N and clinicopathologic features were analyzed and the prognostic impact on overall survival (OS) or disease‐free survival (DFS) was also investigated. Mean and median levels of sGPC3N in healthy controls were 110.12 and 115.95 pg mL−1, respectively, with 185.52 pg mL−1 (mean + 2 SD) being set as the upper limit of the normal range. In HCC patients, sGPC3N levels were significantly increased (mean/median, 405.16/236.19 pg mL−1) compared to healthy controls (p < 0.0001), and 60% of HCC cases (69/115) showed sGPC3N levels that were higher than the upper normal limit. High sGPC3N levels were significantly associated with serum AFP level, high Child‐Pugh score and positive HCV. Kaplan–Meier analysis indicated that elevated pre‐operative sGPC3N was associated with shorter OS and DFS after hepatectomy (p ≤ 0.01). Multivariate analysis revealed elevated sGPC3N as an independent poor prognostic marker for OS (p < 0.05) and DFS (p < 0.01). The pre‐operative sGPC3N level serves as an independent prognostic biomarker in HCC patients.

Intraoperative squash and touch cytology of chondroid chordoma of the skull base. Report of a case with immunocytochemical and immunohistochemical studies.

BACKGROUND Chondroid chordoma is a rare variant of chordoma and is usually located in the sphenooccipital region. This tumor shows clinical and histologic features common to both conventional chordoma and low grade chondrosarcoma and has a better prognosis than either of those lesions. To our knowledge, there has been no English language report describing its cytologic features. CASE The cytologic features of skull base chondroid chordoma observed in intraoperative crush and touch preparations from a 33-year-old female are reported. Touch cytology revealed round or stellate cells distributed in a mucoid background without a typical epithelial cordlike arrangement. The cells had variably vacuolated cytoplasm and round or oval nuclei and showed slight cellular pleomorphism. May-Giemsa staining was superior to Papanicolaou staining in demonstrating the mucoid matrix and vacuolated cytoplasm of the tumor cells. Additionally, crush preparations were effective in demonstrating well-differentiated chondroid elements. Immunocytochemistry with positivity for S-100 protein and cytokeratins was an essential adjunct in the cytologic diagnosis of chordoma and helped in distinguishing it from other chondrogenic tumors. CONCLUSION It is possible and advantageous to diagnose chondroid chordoma with a combination of cytologic and immunocytochemical studies of intraoperative crush and touch preparations in conjunction with clinical and radiographic information.

Cytology of primary cutaneous Langerhans cell histiocytosis with a malignant phenotype. A case report.

BACKGROUND Langerhans cell histiocytosis (LCH) is a proliferative disorder of Langerhans cells, but the nature of LCH, whether reactive, benign, or malignant and neoplastic, is controversial. We encountered a case of LCH showing a malignant phenotype initially localized in the skin of an elderly woman. Since there is no other report on the cytologic appearance of primary cutaneous LCH or on LCH with a malignant phenotype, we compared the cytologic features of this case with those of benign cases at other sites reported in the literature. CASE A 74-year-old woman presented with a gradually enlarging and partially ulcerated skin lesion expanding both sides of her right hand. On histologic and ultrastructural analyses of surgically resected tissue, we diagnosed the lesion as Langerhans cell histiocytosis originating in the skin. Although the patient had no recurrence or metastases for six months after surgical resection of the primary skin lesion and radiation therapy, the tumor extended multisystemically, and the patient died of multiple organ failure 14 months after the initial diagnosis. CONCLUSION Imprint and scrape cytology of multiple skin lesions six months after surgery was useful in immediately diagnosing the recurrent LCH. The tumor cells had indented, twisted or grooved nuclei, and some had intranuclear inclusions. Immunocytochemically the cells were positive for CD1a and S-100 protein. Numerous eosinophils were seen in the background.

Russell body gastritis with Dutcher bodies evaluated using magnification endoscopy

Russell body gastritis (RBG) is an unusual type of chronic gastritis characterized by marked infiltration of Mott cells, which are plasma cells filled with spherical eosinophilic bodies referred to as Russell bodies. It was initially thought that Helicobacter pylori (H. pylori) infection was a major cause of RBG and that the infiltrating Mott cells were polyphenotypic; however, a number of cases of RBG without H. pylori infection or with monoclonal Mott cells have been reported. Thus, diagnostic difficulty exists in distinguishing RBG with monoclonal Mott cells from malignant lymphoma. Here, we report an unusual case of an 86-year-old-Japanese man with H. pylori-positive RBG. During the examination of melena, endoscopic evaluation confirmed a 13-mm whitish, flat lesion in the gastric antrum. Magnification endoscopy with narrow-band imaging suggested that the lesion was most likely a poorly differentiated adenocarcinoma. Biopsy findings were consistent with chronic gastritis with many Mott cells with intranuclear inclusions referred to as Dutcher bodies. Endoscopic submucosal dissection confirmed the diagnosis of RBG with kappa-restricted monoclonal Mott cells. Malignant lymphoma was unlikely given the paucity of cytological atypia and Ki-67 immunoreactivity of monoclonal Mott cells. This is the first reported case of RBG with endoscopic diagnosis of malignant tumor and the presence of Dutcher bodies.

A case of a pleomorphic hyalinizing angiectatic tumor of soft parts with intracytoplasmic hemosiderin pigment apparent upon fine‐needle aspiration cytology

Pleomorphic hyalinizing angiectatic tumors of soft parts are extremely rare low‐grade mesenchymal lesions that frequently occur subcutaneously, especially in the lower extremity. The tumor is histologically characterized by sheets of plump, spindled or rounded cells, and clusters of ectatic blood vessels. It also has a number of previously characterized cytological features such as pleomorphic cells, intranuclear pseudoinclusion, and intracytoplasmic hemosiderin pigments. However, intracytoplasmic hemosiderin has not been carefully evaluated in cytology specimens. Here, we report the case of a 56‐year‐old Japanese man with an encapsulated pleomorphic hyalinizing angiectatic tumor of soft parts that included fine and coarse hemosiderin‐laden tumor cells. The tumor was clinically followed up as a hematoma, but malignant tumors, including malignant melanoma, were suspected because aspiration cytology specimens contained pleomorphic cells with intracytoplasmic brown pigments. The tumor was closely associated with an intratumoral hematoma and a few microscopic satellite lesions. Pleomorphic hyalinizing angiectatic tumor of soft parts should be included in the differential cytological diagnosis of soft tissue tumors if the three cytological features described earlier are present. Enucleation therapy could facilitate local recurrence, as the tumor may have the potential to infiltrate surrounding soft tissue or form satellite lesions. Diagn. Cytopathol. 2015;43:407–411.

Diagnosis of pediatric neuroblastoma by urine cytology: A case report

Neuroblastomas are embryonal tumors arising from the neuronal crest cells of the synaptic nervous system. Findings from aspiration cytology have been reported, but there have been no reports of urine cytology findings. Here, we report a case of pediatric neuroblastoma characterized by urine cytology. A 2‐year‐old boy presented with abdominal pain, nausea, and loss of appetite. Computed tomography revealed a large tumor in the left suprarenal region with massive infiltration into the kidney. Urinary cytology showed highly cellular clusters composed of small, round, atypical cells with little cytoplasm and high nuclear/cytoplasmic ratio; nuclear molding was also noted in some places. Immunocytochemical staining was positive for synaptophysin and chromogranin A, and neuroblastoma was suggested by urine cytology. A biopsy of the left adrenal tumor later confirmed a diagnosis of poorly differentiated neuroblastoma. Urine cytology may be useful for rapid diagnosis and management of similar cases.

Cytological findings and BCL10 expression in pancreatic acinar cell carcinoma: A Case Report.

BCL10 was recently demonstrated to be a biomarker for pancreatic acinar cell carcinoma, but whether altered BCL10 expression can be detected in cell block specimens is unclear. Here, we report a pancreatic acinar cell carcinoma with cytological findings that showed BCL10 expression in a cell block. A 72‐year‐old man presented with a pancreatic tumor and underwent endoscopic ultrasound‐fine needle aspiration (EUS‐FNA) with additional passes performed for cell block preparation. The EUS‐FNA cytology showed loose cohesive clusters with focal acinar‐ or gland‐like‐structures and prominent nucleoli. The preoperative diagnosis was well differentiated adenocarcinoma, and he underwent a pancreaticoduodenectomy. Histological examination revealed an acinar tumor structure with tumor cells staining positive for BCL10 and trypsin. The cell block specimen also demonstrated strong and diffuse BCL10‐positive staining. Based on these findings, this tumor was diagnosed as acinar cell carcinoma of the pancreas. This case demonstrates that BCL10 expression within cell blocks facilitates a differential diagnosis of acinar cell carcinoma. Diagn. Cytopathol. 2017;45:247–251.

A case of intracranial chondrosarcoma, with special reference to cytologic differentiation from chordoma and chondroid chordoma.

背景:頭蓋内原発の軟骨肉腫はまれな腫瘍で, 多くは頭蓋底に発生する. 組織像が通常の脊索腫や軟骨腫様脊索腫に類似し, 鑑別診断の困難な場合があるが, 両腫瘍の予後は大きく異なり, その鑑別は臨床上重要である. 頭蓋底原発軟骨肉腫の1例を, 過去に経験した脊索腫9例, 軟骨腫様脊索腫1例との比較を通して, その細胞像と鑑別点について報告する.症例:症例は26歳男性, 近医にてトルコ鞍背側～右側頭骨内側部にかけて腫瘍を指摘され, 当院脳神経外科にて腫瘍切除術を受けた. 術中細胞診では, 粘液様物質を背景に腫瘍細胞が散在性に出現し, 核は小型で円形から卵円形, 核の腫大や二核も認めた. 軟骨への分化を示唆する1acunar structureを認めたが, 軟骨腫様脊索腫にみられる上皮様細胞接着や典型的な担空胞細胞 (physaliphorous cells) は認められず, 軟骨肉腫と診断した. 術後の組織所見, 免疫染色所見 (S-100蛋白+, Vimentin+, EMA-, Cytokeratins-) もこれを支持した.結論:粘液様背景や軟骨への分化を正確に捉え, さらに細胞間接着性を詳細に観察すれば, 脊索腫, 軟骨腫様脊索腫との細胞診による鑑別も可能と考えた.

A case of clear cell sarcoma of the Achilles tendon.

13歳女性. 左アキレス腱部に痺痛, 腫脹を認め, 2年後に摘出術を施行された. 病変はアキレス腱に存在し, 一部周囲結合組織と癒着していた. 術中細胞診標本では, 比較的均一で紡錘形ないし多角形の腫瘍細胞が多数みられ, 核は類円形でクロマチンは細穎粒状, 通常1個の明瞭な核小体を認めた. 細胞質は淡明で比較的豊富であった. メラニン穎粒は認められなかったが, 腫瘍細胞の多くはS-100蛋白, HMB45 (抗メラノーマ特異抗体) が陽性で, 電顕的にメラノゾームが観察された. 明細胞肉腫は, 明瞭な核小体を有することや免疫組織化学が診断に有用なことから, 臨床所見を加味すれば術中捺印細胞診で診断が可能と考えられる.