Coexpression of MCT1 and MCT4 in ALK-positive Anaplastic Large Cell Lymphoma: Diagnostic and Therapeutic Implications.

In solid tumors, glycolytic cancer or stromal cells export lactates through monocarboxylate transporter (MCT) 4, while oxidative cancer or stromal cells take up lactates as metabolic fuels or signaling molecules through MCT1. CD147 acts as a chaperone of MCT1 or MCT4. Unlike solid tumors, malignant lymphomas have a peculiar tumor microenvironment. To investigate the metabolic phenotype of malignant lymphoma associated with lactate transport, we analyzed immunohistochemical expressions of MCT1, MCT4, and CD147 in 247 cases of various malignant lymphomas. Surprisingly, both MCT1 and MCT4 were diffusely expressed on tumor cell membranes in all cases (11/11, 100%) of anaplastic lymphoma kinase (ALK) (+) anaplastic large cell lymphoma (ALCL). In contrast, only MCT1 was diffusely expressed in tumor cells of ALK(-) ALCL, as well as in B-cell, natural killer/T-cell, T-cell, and classic Hodgkin lymphomas. In these lymphomas, MCT4 expression was mostly localized to adjacent stromal cells. The pattern of diffuse membranous MCT1 and partial MCT4 expressions in tumor cells was observed in 1 case each of peripheral T-cell lymphoma (1/15, 6.7%) and multiple myeloma (1/34, 2.9%). CD147 was diffusely expressed in all types of lymphoma tumor and/or stromal cells. In conclusion, ALK(+) ALCL has a unique metabolism showing high coexpression of MCT1 and MCT4 in tumor cells. Because only ALK(+) ALCL overexpresses MCT4, immunostaining for MCT4 together with ALK is very useful for differential diagnosis from ALK(-) ALCL or peripheral T-cell lymphoma. Moreover, dual targeting against MCT1 and MCT4 would be an appropriate therapeutic approach for ALK(+) ALCL.

Comparison of papanicolaou smear and human papillomavirus (HPV) test as cervical screening tools: can we rely on HPV test alone as a screening method? An 11-year retrospective experience at a single institution.

BACKGROUND: The decrease in incidence of cervical dysplasia and carcinoma has not been as dramatic as expected with the development of improved research tools and test methods. The human papillomavirus (HPV) test alone has been suggested for screening in some countries. The National Cancer Screening Project in Korea has applied Papanicolaou smears (Pap smears) as the screening method for cervical dysplasia and carcinoma. We evaluated the value of Pap smear and HPV testing as diagnostic screening tools in a single institution. METHODS: Patients co-tested with HPV test and Pap smear simultaneously or within one month of each other were included in this study. Patients with only punch biopsy results were excluded because of sampling errors. A total of 999 cases were included, and the collected reports encompassed results of smear cytology, HPV subtypes, and histologic examinations. RESULTS: Sensitivity and specificity of detecting high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were higher for Pap smears than for HPV tests (sensitivity, 97.14%; specificity, 85.58% for Pap smears; sensitivity, 88.32%; specificity, 54.92% for HPV tests). HPV tests and Pap smears did not differ greatly in detection of low-grade squamous intraepithelial lesion (85.35% for HPV test, 80.31% for Pap smears). When atypical glandular cells were noted on Pap smears, the likelihood for histologic diagnosis of adenocarcinoma following Pap smear was higher than that of high-risk HPV test results (18.8 and 1.53, respectively). CONCLUSIONS: Pap smears were more useful than HPV tests in the diagnosis of HSIL, SCC, and glandular lesions.

Adult intussusception caused by colonic anisakis: A case report.

BACKGROUND: Colo-colonic intussusception is an uncommon phenomenon in an adult. Adult intussusception accounts for < 5% of total cases, and the colo-colonic type is < 30% of cases. Although surgical management has been the treatment of choice for intestinal intussusception in adults, because most frequent causes for adult intussusception are malignant in origin, the importance of the roles of preoperative colonoscopic evaluation has recently been emerging. CASE SUMMARY: We report an extremely rare case of adult colo-colonic intussusception caused by colonic anisakiasis and successfully treated by endoscopic removal of the Anisakis body. A 59-year-old man visited the emergency department due to 1 day of lower abdominal colicky pain. Abdominopelvic computed tomography (APCT) revealed the presence of mid-transverse colon intussusception without definite necrosis, which was possibly related with colorectal cancer. Because there was no evidence of necrosis at the intussusception site, a colonoscopy was performed to target the colonic lesion and obtain tissue for a histopathological diagnosis. An Anisakis body was found when inspecting the suspicious colonic lesion recorded by APCT. The Anisakis body was removed with forceps assisted by colonoscopy. The patient's symptoms improved dramatically after removing the Anisakis. A reduced colon without any pathological findings was seen on the follow-up APCT. Without any further treatment, the patient was discharged 5 d after the endoscopy. CONCLUSION: When colonic intussusception without necrosis occurs in an adult, physician should consider a colonoscopy to exclude causes cured by endoscopy.

Intraoperative Frozen Cytology of Central Nervous System Neoplasms: An Ancillary Tool for Frozen Diagnosis.

BACKGROUND: Pathologic diagnosis of central nervous system (CNS) neoplasms is made by comparing light microscopic, immunohistochemical, and molecular cytogenetic findings with clinicoradiologic observations. Intraoperative frozen cytology smears can improve the diagnostic accuracy for CNS neoplasms. Here, we evaluate the diagnostic value of cytology in frozen diagnoses of CNS neoplasms. METHODS: Cases were selected from patients undergoing both frozen cytology and frozen sections. Diagnostic accuracy was evaluated. RESULTS: Four hundred and fifty-four cases were included in this retrospective single-center review study covering a span of 10 years. Five discrepant cases (1.1%) were found after excluding 53 deferred cases (31 cases of tentative diagnosis, 22 cases of inadequate frozen sampling). A total of 346 cases of complete concordance and 50 cases of partial concordance were classified as not discordant cases in the present study. Diagnostic accuracy of intraoperative frozen diagnosis was 87.2%, and the accuracy was 98.8% after excluding deferred cases. Discrepancies between frozen and permanent diagnoses (n = 5, 1.1%) were found in cases of nonrepresentative sampling (n = 2) and misinterpretation (n = 3). High concordance was observed more frequently in meningeal tumors (97/98, 99%), metastatic brain tumors (51/52, 98.1%), pituitary adenomas (86/89, 96.6%), schwannomas (45/47, 95.8%), high-grade astrocytic tumors (47/58, 81%), low grade astrocytic tumors (10/13, 76.9%), non-neoplastic lesions (23/36, 63.9%), in decreasing frequency. CONCLUSIONS: Using intraoperative cytology and frozen sections of CNS tumors is a highly accurate diagnostic ancillary method, providing subtyping of CNS neoplasms, especially in frequently encountered entities.

Squamous Cell Carcinoma of the Extrahepatic Common Hepatic Duct.

We report a rare case of hilar squamous cell carcinoma. A 62-year-old Korean woman complaining of nausea was referred to our hospital. Her biliary computed tomography revealed a 28 mm-sized protruding solid mass in the proximal common bile duct. The patient underwent left hemihepatectomy with S1 segmentectomy and segmental excision of the common bile duct. Microscopically, the tumor was a moderately differentiated squamous cell carcinoma of the extrahepatic bile duct, without any component of adenocarcinoma or metaplastic portion in the biliary epithelium. Immunohistochemically, the tumor was positive for cytokeratin (CK) 5/6, CK19, p40, and p63. Squamous cell carcinoma of the extrahepatic bile duct is rare. To date, only 24 cases of biliary squamous cell carcinomas have been reported. Here, we provide a clinicopathologic review of previously reported extrahepatic bile duct squamous cell carcinomas.

Nuclear features of papillary thyroid carcinoma: Comparison of Core needle biopsy and thyroidectomy specimens.

BACKGROUND: Core needle biopsy (CNB) has been used as an alternative or a complementary method for diagnosis of thyroid nodules. However, morphological analysis of the nuclear features of papillary thyroid carcinoma (PTC) cells obtained via CNB remains unclear. Hence, we examined the differences between the PTC nuclear features in CNB and thyroidectomy specimens. METHODS: Ten PTC patients, who underwent both CNB and thyroidectomy, were selected. Microscopic photographs of three representative areas of the PTC and adjacent parenchyma were taken. Ten cells per photograph were chosen, and 1200 cells were evaluated (300 PTC and 300 follicular cells in the CNB and thyroidectomy specimens, respectively). The area, circumference, major axis, and minor axis were measured using an image analyzer. Detailed nuclear features (size and shape, membrane irregularity, chromatin characteristics) were scored using a 3-point scale. RESULTS: The mean nuclear area, circumference, major axis, and minor axis of PTC cells in the CNB specimen were 1.76, 1.34, 1.34, and 1.29 times larger than those of the follicular cells (p<0.001); similar results were seen in the thyroidectomy specimens (2.04, 1.41, 1.37, and 1.37: p<0.001). Comparative analysis revealed that these parameters were significantly smaller in the CNB specimens than those in the thyroidectomy specimens (p<0.001). Nuclear grades were also lower in the former owing to poor chromatin characteristics (clearing and margination) (p<0.01). CONCLUSION: Considering that the PTC nuclei in CNB specimens are smaller with fewer irregularities and less clear than those in thyroidectomy specimens, we need to emphasize caution when using CNB specimens for diagnosis.

Improvement of diagnostic performance of pathologists by reducing the number of pathologists responsible for thyroid fine needle aspiration cytology: An institutional experience.

BACKGROUND: Various efforts have been made to improve the diagnostic accuracy of thyroid fine needle aspiration (FNA) cytology. We changed the diagnostic system by reducing the number of pathologists responsible for the thyroid FNA cytology in the routine work, and analyzed the effect on the pathologist's diagnostic performance. METHODS: Since March 1, 2015, 3 pathologists have been responsible for diagnostic thyroid FNA, previously undertaken by 9 equally. We compared the prechange period (three months, 319 nodules) and the postchange period (12 months, 1194 nodules). RESULTS: The turnaround time was shortened from 1.4 ± 0.7 days to 0.9 ± 0.5 days (P < .001). The utilization rate of the Bethesda system for Reporting Thyroid Cytopathology (TBSRTC) increased from 92.5% to 99.8%. Diagnostic rates of categories that are confirmative [II (benign) and VI (malignant)] increased, while the inadequate (I) or indeterminate (III) categories decreased. With category IV (follicular neoplasm), a challenging category in our country, an elevated malignancy rate was found at follow-up. Overall, the diagnostic performance was improved in terms of sensitivity (from 98.5% to 99.2%) and specificity (from 94.4% to 98.4%), with reduced false-negative rates (from 1.5% to 0.8%) and false-positive rates (from 2.9% to 1.1%). The area under the receiver operating characteristic curve increased from 0.861 to 0.958. CONCLUSION: Reducing the number of pathologists responsible for diagnostic thyroid FNA cytology resulted in a higher utilization rate of TBSRTC, and more rapid and accurate diagnosis.

Factors associated with parametrial involvement in patients with stage IB1 cervical cancer: Who is suitable for less radical surgery?

OBJECTIVE: To detect the possible clinicopathologic factors associated with parametrial involvement in patients with stage IB1 cervical cancer and to identify a cohort of patients who may benefit from less radical surgery. METHODS: We retrospectively reviewed 120 patients who underwent radical hysterectomy and pelvic lymphadenectomy as treatment for stage IB1 cervical cancer. RESULTS: Overall, 18 (15.0%) patients had parametrial tumor involvement. Tumor size larger than 2 cm, invasion depth greater than 1 cm, presence of lymphovascular space involvement (LVSI), corpus involvement, and positive lymph nodes were statistically associated with parametrial involvement. Multivariate analysis for other factors showed invasion depth >1 cm (P=0.029), and corpus involvement (P=0.022) were significantly associated with parametrial involvement. A subgroup with tumor size smaller than 2 cm showed no parametrial involvement, regardless of invasion depth or presence of LVSI. CONCLUSION: Tumor size smaller than 2 cm showed no parametrial involvement, regardless of invasion depth or presence of LVSI. Invasion depth >1 cm and corpus involvement were significantly associated with parametrial involvement in multivariate analysis. These finding may suggest that tumor size may a strong predictor of parametrial involvement in International Federation of Gynecology and Obstetrics stage IB1 cervical cancer, which can be used to select a subgroup population for less radical surgery.

Pediatric intracerebral histiocytic sarcoma with rhabdoid features: Case report and literature review.

A 16-year-old boy presented with marked weight loss, weakness of the left extremities and dizziness of 2 months duration and vomiting for 2 days. Brain MRI showed an approximately 6.5 × 5.3 cm-sized huge heterogeneous enhancing mass located in the corpus callosum, extending into the lateral ventricle. Open biopsy showed that the lesion consisted of lymphoplasmacytes and plump histiocytes with rhabdoid morphology, which were stained with S-100 protein, CD68 (KP1) and negative for CD1a. Histiocytic tumor was initially diagnosed. Chemotherapy using methotrexate, 6-mercaptopurine, vinblastine, interferon-alpha and dexamethasone was performed. After 5 months, partial removal was done. Microscopically, plump and bizarre tumor cells as well as rhabdoid features were found. Occasional spindle cells and necrosis were also found. These cells were positive for CD163, CD68, lysozyme, CD4, INI-1 and BRG1. BRAF V600E mutation was detected. The lesion was finally diagnosed as histiocytic sarcoma. Radiotherapy (6000 cGy in 30 fractions) was done. Both cerebral and extracerebral histiocytic sarcomas have long been diagnosed by unclarified criteria; its rarity as well as previously unclarified criteria can easily lead to a misinterpretation. Histiocytic sarcoma of the CNS is exceptionally rare in children, associated with an exceptionally poor prognosis. To date, only seven cases of pediatric cerebral histiocytic sarcomas have been reported. The present case is the first pediatric case showing BRAF V600E-mutated intracerebral histiocytic sarcoma.

Clinicopathologic Characteristics and Mutational Status of Succinate Dehydrogenase Genes in Paraganglioma of the Urinary Bladder: A Multi-Institutional Korean Study.

CONTEXT: - Because of the limited number of available primary bladder paraganglioma (PBPG) cases, the rates of succinate dehydrogenase (SDH) mutations and the clinicopathologic characteristics of SDH-deficient tumors have not been fully studied. OBJECTIVE: - To define the clinicopathologic and molecular characteristics of PBPGs. DESIGN: - A total of 52 PBPGs were collected retrospectively. SDHA and SDHB immunohistochemical stains were performed. In cases of SDHB expression loss, mutation analyses of SDHB, SDHC, and SDHD were performed. RESULTS: - The clinicopathologic features were analyzed for 52 cases (M:F = 27:25), with a mean age of 56 years (range, 22-79 years). Tumor sizes were 0.5 to 8 cm (mean, 2.4 cm). Tumor necrosis was present in 5 of 52 cases (10%), involvement of muscularis propria in 41 (79%), and lymphovascular tumor invasion in 6 (12%). During a mean follow-up period of 41 months (range, 1-161 months), 3 of 52 patients (6%) developed metastases, but no one died from the disease. Immunohistochemistry for SDHA and SDHB showed that all cases were SDHA intact. Among them, 43 cases had intact SDHB, whereas 9 cases were SDHB deficient. Compared with the SDHB-intact cases, the SDHB-deficient cases were characterized by large tumor sizes (4.5 versus 1.9 cm; P < .001), a higher number of mitoses per 10 high-powered fields (2.6 versus 0.1; P = .002), and frequent lymphovascular tumor invasion (33% versus 7%; P = .02) and metastases (22% versus 2%; P = .02). Mutational analyses for SDHB, SDHC, and SDHD were performed in 9 SDHB-deficient cases. Among them, 6 cases were successfully sequenced and revealed SDHB mutations only. CONCLUSIONS: - Large tumor size, a higher number of mitoses, and the presence of lymphovascular tumor invasion and SDHB mutations suggest malignant paraganglioma.

Primary ovarian mixed strumal and mucinous carcinoid arising in an ovarian mature cystic teratoma.

A 39-year-old woman presented with low back pain lasting for several weeks. Abdominopelvic computed tomography showed an ovarian cystic mass with an enhancing solid portion, fat and internal calcification. A right salpingo-oophorectomy was performed. A 9.7 cm round multiseptated cystic mass showed pathology of mature cystic teratoma and contained a solid portion, measuring 4.2 cm, composed mainly of carcinoid cells arranged in a trabecular-insular configuration admixed with surrounding thyroid follicles containing colloid. Juxtaposed were several nests of columnar cells interspersed with goblet cells and extracellular mucin pools. In the cyst wall of the teratoma, the lining of pseudostratified columnar cells was occasionally mixed with goblet cells transforming to the carcinoid portion. Immunohistochemically, both mucinous and strumal carcinoids were positive for polyclonal carcinoembryonic antigen, caudal type homeobox 2, cytokeratin (CK)7, CK20, synaptophysin, CD56 and focally positive for chromogranin. Thyroid follicles were positive for thyroid transcription factor-1 and thyroglobulin. After gastrointestinal and respiratory tract evaluation, no evidence of primary tumor, including omentum, was observed. The mass was diagnosed as a mixed strumal and mucinous type carcinoid associated with a mature cystic teratoma.

Rare Case of Anal Canal Signet Ring Cell Carcinoma Associated with Perianal and Vulvar Pagetoid Spread.

A 61-year-old woman was referred to surgery for incidentally found colonic polyps during a health examination. Physical examination revealed widespread eczematous skin lesion without pruritus in the perianal and vulvar area. Abdominopelvic computed tomography showed an approximately 4-cm-sized, soft tissue lesion in the right perianal area. Inguinal lymph node dissection and Mils' operation extended to perianal and perivulvar skin was performed. Histologically, the anal canal lesion was composed of mucin-containing signet ring cells, which were similar to those found in Pagetoid skin lesions. It was diagnosed as an anal canal signet ring cell carcinoma (SRCC) with perianal and vulvar Pagetoid spread and bilateral inguinal lymph node metastasis. Anal canal SRCC is rare, and the current case is the third reported case in the English literature. Seven additional cases were retrieved from the world literature. Here, we describe this rare case of anal canal SRCC with perianal Pagetoid spread and provide a literature review.

Crush Cytology of Secretory Meningioma: A Case Report.

Secretory meningioma, a histologic subtype of meningioma of World Health Organization grade 1, is clinically significant because it is frequently accompanied by peritumoral brain edema. The patient was a 53-year-old woman suffering from dysarthria and motor weakness of the right arm. Enhanced magnetic resonance images showed an enhancing mass measuring 2.5 cm in size located in the right parietal convexity. Intraoperative squash cytology showed moderately cellular smears composed mainly of clusters of ovoid cells with scattered whorl formations. The cells had round nuclei and a moderate amount of eosinophilic cytoplasm with ill-defined cell borders. Neither atypia nor mitosis was observed. Some scattered round shaped eosinophilic refractile hyaline globules, measuring from 5 to 25 µm, were observed, and a periglobular halo was occasionally observed. The diagnosis of secretory meningioma should be made as early as possible so that neurosurgeons can prevent postoperative aggravation of peritumoral edema. We emphasize that cytologic findings including eosinophilic, non-fibrillary cytoplasm with eosinophilic refractile hyaline globules are helpful in differentiating secretory meningioma from other subtypes of meningioma, primary and metastatic brain tumors.

Oncocytic Renal Cell Carcinoma with Tubulopapillary Growth Having a Fat Component.

We report a rare case of oncocytic renal cell carcinoma (RCC) with tubulopapillary growth in the background of tuberculous end-stage kidney disease. Histology of the renal mass consisted of oncocytic cells forming solid, thin tubules and rare papillae. The tumor had abundant eosinophilic oncocytic cells containing occasional cytoplasmic Mallory body-like hyaline globules and a tiny focus of clear cells with intervening mature fat. Both the oncocytic cells and clear cells were immunoreactive for a-methylacyl-CoA racemase, vimentin, pancytokeratin, and CD10, and negative for transcription factor E3, CD15, human melanoma black 45, and c-kit. Mallory body-like hyaline globules were positive for CAM 5.2 and periodic acid-Schiff with or without diastase. Ultrastructurally, the tumor cells had abundant cytoplasmic mitochondria. The present case is a rare case of oncocytic RCC with tubulopapillary growth pattern. The case is unique in that the tumor was mixed with fat component, which is not common in RCC and thus can lead to misdiagnosis.

Comparison of Cytologic Characteristics between Adenoid Cystic Carcinoma and Adenoid Basal Carcinoma in the Uterine Cervix.

BACKGROUND: Adenoid cystic carcinoma (ACC) and adenoid basal carcinoma (ABC) are rare in the uterine cervix. ACC is more aggressive than ABC, thus accurate differential diagnosis is important. In this study, we identified cytologic features useful in distinguishing these two tumors for diagnosis. METHODS: Three cases of ACC and five cases of ABC were selected for this study. Cervicovaginal smear slides were reviewed retrospectively, and the area, circumference, major axis, and minor axis of nuclei were measured using an image analyzer. RESULTS: ACC displayed three-dimensional clusters with a small acini pattern. ABC displayed peripheral palisading without an acini pattern. The nuclei of ACC were more irregular and angulated than those of ABC, and the former showed a coarsely granular chromatin pattern. The nucleic area, circumference, major axis, and minor axis were 18.556±8.665 µm(2), 23.320±11.412 µm, 5.664±1.537 µm, and 4.127±1.107 µm in ACC and 11.017±4.440 µm(2), 15.920±5.664 µm, 4.612±1.025 µm, and 3.088±0.762 µm in the cases of ABC. All measured values showed statistically significant difference (p < .001). CONCLUSIONS: Although the nuclei of both of these tumor types were oval shaped, inferred from the ratio of minor axis to major axis (0.728 in ACC and 0.669 in ABC), the area of nuclei was approximately 1.7 times larger in ACC than in ABC. Distinguishing nucleic features, including area, morphology, and chromatin pattern, may be helpful in making a correct diagnosis.

Squash Cytology of a Dural-Based High-Grade Chondrosarcoma May Mimic That of Glioblastoma in the Central Nervous System.

BACKGROUND: Intracranial chondrosarcoma is rare, and most cases occur in the skull base. Intradural chondrosarcoma is even rarer. CASE: Here, we describe a case of dural chondrosarcoma with a radiation history for nasopharyngeal carcinoma and a radical prostatectomy for prostatic cancer 15 and 8 years earlier, respectively. A 67-year-old man presented with a 3-week memory disturbance and dysarthria. Computed tomography and magnetic resonance images of the brain revealed a dural-based mass in the left temporal area. Under the impression of a glioblastoma, a resection and an intraoperative squash cytology were done. A necrotic dirty background as well as bluish-to-pinkish myxoid stroma were characteristic; the nuclei of highly pleomorphic tumor cells were hyperchromatic to vesicular with an occasional ground-glass appearance. The cytoplasm was of an eosinophilic hyalinized condensed morphology with an occasional granular appearance. Histologically, the lobulated mass was composed of hypercellular lobules of well-differentiated chondrocytes intermixed with anaplastic pleomorphic cells and diagnosed as a conventional grade III chondrosarcoma. These cells were immunoreactive for D2-40, S-100 protein and vimentin. Brain invasion was also found. CONCLUSION: Albeit rare, dural-based chondrosarcomas should be considered in the differential diagnosis for meningeal tumors, especially in the case of previous radiation therapy.