Prognostic impact of tumor-associated neutrophils in breast cancer.

OBJECTIVES: Neutrophils are the most common type of leukocyte in mammals and play an essential role in the innate immune system and anti-cancer responses. However, recent studies identified the presence of tumor-associated neutrophils (TANs) as a poor prognostic factor. The present study investigated whether relationships exist between TANs and the clinicopathological factors and genetic status of breast cancer. METHODS: A total of 196 breast cancer patients with sufficient biopsy, breast-conserving surgery, or mastectomy specimens between 2014 and 2021 in Hokuto Hospital were included. RESULTS: TANs were individually counted in the tumor stroma (TS) and tumor nest (TN). A higher density of TANs in both TS and TN correlated with tumor size (TS P = 0.010; TN P = 0.001), a high histological grade (TS P < 0.001; TN P < 0.001), the histological type (TS P = 0.009; TN P = 0.034), a high ratio of lymph node metastasis (TS P < 0.001; TN P < 0.001), an advanced stage of cancer (TS P < 0.001; TN P = 0.002), intrinsic subtypes (TS P < 0.001; TN P < 0.001), ERBB2 (TS P < 0.001; TN P < 0.001), MAP3K1 (TS P = 0.002; TN P = 0.023), and TP53 (TS P < 0.001; TN P < 0.001). A higher density of TANs in TS and TN also correlated with shorter disease-free survival and overall survival (P < 0.001). CONCLUSION: The present results suggest that a higher density of TANs correlates with unfavorable prognostic factors in breast cancer. Further research on clinicopathological and genetic factors associated with TANs in breast cancer is needed.

Clinical and Diagnostic Utility of Genomic Profiling for Digestive Cancers: Real-World Evidence from Japan.

The usefulness of comprehensive genomic profiling (CGP) in the Japanese healthcare insurance system remains underexplored. Therefore, this large-scale study aimed to determine the usefulness of CGP in diagnosing digestive cancers. Patients with various cancer types recruited between March 2020 and October 2022 underwent the FoundationOne® CDx assay at the Keio PleSSision Group (19 hospitals in Japan). A scoring system was developed to identify potentially actionable genomic alterations of biological significance and actionable genomic alterations. The detection rates for potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to companion diagnosis (CDx), as well as the signaling pathways associated with these alterations in each digestive cancer, were analyzed. Among the 1587 patients, 547 had digestive cancer. The detection rates of potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to CDx were 99.5%, 62.5%, and 11.5%, respectively. APC, KRAS, and CDKN2A alterations were frequently observed in colorectal, pancreatic, and biliary cancers, respectively. Most digestive cancers, except esophageal cancer, were adenocarcinomas. Thus, the classification flowchart for digestive adenocarcinomas proposed in this study may facilitate precise diagnosis. CGP has clinical and diagnostic utility in digestive cancers.

BRCA1/2 reversion mutations in a pan-cancer cohort.

Tumor sensitivity to platinum (Pt)-based chemotherapy and poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors is increased by homologous recombination deficiency-causing mutations; in particular, reversion mutations cause drug resistance by restoring protein function. Treatment response is predicted by breast cancer susceptibility gene 1/2 (BRCA1/2) mutations; however, BRCA1/2 reversion mutations have not been comprehensively studied in pan-cancer cohorts. We aimed to characterize BRCA1/2 reversion mutations in a large pan-cancer cohort of Japanese patients by retrospectively analyzing sequencing data for BRCA1/2 pathogenic/likely pathogenic mutations in 3738 patients with 32 cancer types. We identified somatic mutations in tumors or circulating cell-free DNA that could restore the ORF of adverse alleles, including reversion mutations. We identified 12 (0.32%) patients with somatic BRCA1 (n = 3) and BRCA2 (n = 9) reversion mutations in breast (n = 4), ovarian/fallopian tube/peritoneal (n = 4), pancreatic (n = 2), prostate (n = 1), and gallbladder (n = 1) cancers. We identified 21 reversion events-BRCA1 (n = 3), BRCA2 (n = 18)-including eight pure deletions, one single-nucleotide variant, six multinucleotide variants, and six deletion-insertions. Seven (33.3%) reversion deletions showed a microhomology length greater than 1 bp, suggesting microhomology-mediated end-join repair. Disease course data were obtained for all patients with reversion events: four patients acquired mutations after PARP-inhibitor treatment failure, two showed somatic reversion mutations after disease progression, following Pt-based treatment, five showed mutations after both treatments, one patient with pancreatic cancer and BRCA1 reversion mutations had no history of either treatment. Although reversion mutations commonly occur in BRCA-associated cancers, our findings suggest that reversion mutations due to Pt-chemotherapy might be correlated with BRCA1/2-mediated tumorigenesis even in non-BRCA-associated histologies.

Liposarcoma of the pleural cavity.

Liposarcoma rarely occurs in the pleura or thoracic cavity, and few reports appear in the literature. We hypothesized that combining clinicopathologic, immunohistochemical, and fluorescence in situ hybridization methods would allow definite diagnoses. Using formalin-fixed, paraffin-embedded blocks, we examined 6 atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLPS), 5 dedifferentiated liposarcomas (DDLPSs), 2 pleomorphic liposarcomas, and 1 myxoid liposarcoma (MLPS). We used the Kaplan-Meier method and the Wilcoxon test for survival analysis for prognostic factor evaluation. Histologically, ALT/WDLPS was composed of a relatively mature adipocytic proliferation, accompanied by some lipoblasts. DDLPS exhibited round-to-oval tumor cells with a high nucleus-to-cytoplasm ratio that had proliferated in nests, accompanied in case 10 by some giant cells but no fatty cells. The pleomorphic type contained a varying proportion of pleomorphic lipoblasts. MLPS displayed uniform round- to oval-shaped cells and small signet-ring lipoblasts in a myxoid stroma. Immunohistochemically, 11 (79%), 11 (79%), and 10 (71%) of 14 cases were positive for S-100, p16, and CDK4, respectively. Six of the 14 cases (43%) were positive for MDM2 and adipophilin. One case of ALT/WDLPS and 3 cases of DDLPS exhibited MDM2 amplification by fluorescence in situ hybridization (Vysis LSI MDM2 SpectrumGreen Probe plus Vysis CEP 12 SpectrumOrange probe). ALT/WDLPS was the most favorable type for survival, while adipophilin tended to be a negative prognostic factor for pleural liposarcoma. For a firm diagnosis of liposarcoma in the pleura, immunohistochemistry for CDK4, MDM2, and adipophilin together with MDM2 gene amplification by fluorescence in situ hybridization may be an important diagnostic tool.

Primary Hepatic Angioleiomyoma: A Case Report.

BACKGROUND Primary hepatic angioleiomyoma is a rare mesenchymal tumor that is characterized by blood vessels and smooth muscle. Herein, we report an extremely rare case of primary hepatic angioleiomyoma and discuss the clinicopathological features. CASE REPORT A 60-year-old Mongolian man was diagnosed with a hepatic tumor in the second and third segments of screening in 2012. It had been under control by a physician for 10 years. The patient had discomfort and vague pain in the right side of the abdomen since April 2022. Hepatitis virus markers (hepatitis B and hepatitis C) were negative. Plain computed tomography revealed an 80-mm solitary liver lesion in the left lobe with well-defined margins and heterogeneous enhancement. A left hepatectomy was performed in May 2022. The cut surface of the tumor showed a grayish-white, elastic, hard mass with a diameter of 50×80 mm. Histological findings of the tumor revealed that it was clearly demarcated from the surrounding liver tissues with relatively clear boundaries showing thick, muscle-coated blood vessels with perivascular smooth muscle bundles. Immunohistochemical staining showed that the smooth muscle cells were strongly diffuse and positive for smooth muscle actin. CONCLUSIONS Clinically, primary hepatic angioleiomyoma should be distinguished from other types of liver tumors, especially liver cancer. In combination with our long-term observation and other case reports, we recommend general follow-up if the preoperative pathological diagnosis can be confirmed and the patient has no other symptoms.

Gastric Adenocarcinoma of the Fundic Gland Type: A Case Report.

BACKGROUND Gastric adenocarcinoma of the fundic gland type (GAFG) is an extremely rare neoplasm that consists of a mixed proliferation of oxyntic and chief cells. Differential diagnosis of GAFG is difficult in the absence of infiltration. Here, we report a case of GAFG and discuss the clinicopathological features. CASE REPORT A 78-year-old man was diagnosed with gastritis and reflux esophagitis, status after esophagectomy for carcinoma of the esophagus in 2015. The patient underwent repeated gastric biopsies in 2017 and an atypical epithelium was observed, but no diagnosis was confirmed. There was no evidence of tumor extension in the submucosa. The tumor was resected via endoscopic mucosal resection, and pathological examination was performed. Microscopic findings revealed an oxyntic-type gastric mucosa with atypical dense or dilated glands with abundant pale basophilic cytoplasm and round nuclei with prominent nucleoli. The majority of the tumor cells resembled chief cells, suggesting they were derived from gastric fundic glands. However, the tumor appeared to have no submucosal infiltration or focal stromal desmoplastic reaction. Sections stained positive for MUC6 and pepsinogen-I in chief cells, and H+/K+ ATPase and PDGFRa in parietal cells, but were mostly negative for CDX2, chromogranin A, synaptophysin, and CD10. Sections stained for mib-1 expressed very low proliferative activity, with an average of 10%. Staining for TP53 overexpression was negative. CONCLUSIONS Immunostaining markers are a supportive tool for histological diagnosis of GAFG. However, if there is no infiltration, as in our case, it is difficult to consider it as a malignant tumor. Further elucidation is needed in the future, including an officially accepted diagnostic name.

Tumor-infiltrating B cells and T cells correlate with postoperative prognosis in triple-negative carcinoma of the breast.

BACKGROUND: In this study, we investigated CD20+ TILs in triple-negative breast cancer (TNBC) and their relationship with T lymphocyte subsets (CD4+, CD8+, CD25+, and FOXP3+), including their combined prognostic value using an immunohistochemical staining method. METHODS: We investigated 107 patients with TNBC for whom a full-face section stained by hematoxylin and eosin between 2006 and 2018 at Dokkyo Medical University Hospital was available. RESULTS: The strongest association of infiltrating CD20+ TILs was with CD4+ TILs. There was a significant relationship between CD20+ and CD4+ TILs (r = 0.177; p < 0.001), CD8+ TILs (r = 0.085; p = 0.002), and FOXP3+ TILs (r = 0.0043; p = 0.032). No significant relationships were observed between the CD20+ and CD25+ TILs (r = 0.012; p = 0.264). Multivariate analysis revealed that only the CD20+/FOXP3 ratio was an independent factor for relapse-free survival (p < 0.001) and overall survival (p < 0.001). Patients with tumors highly infiltrated by CD4+, CD8+, and CD20+ TILs had a good prognosis. In contrast, those with tumors weakly infiltrated by CD20+ TILs but highly infiltrated by CD25+ and FOXP3+ TILs had a poor prognosis. CONCLUSIONS: CD20+ TILs may support an increase in CD4+ and CD8+ TILs, which altered the anti-tumor response, resulting in a positive prognosis. CD20+ TILs correlated with FOXP3+ Treg lymphocytes, which were reported to be correlated with a poor prognosis. Our study suggested that TIL-B cells have dual and conflicting roles in TIL-T immune reactions in TNBC.

Prognostic value of tumor-infiltrating B lymphocytes and plasma cells in triple-negative breast cancer.

BACKGROUND: Recent investigations have demonstrated that the tumor microenvironment, including tumor-infiltrating lymphocytes (TILs), is an important factor in tumor growth and development. While the prognostic correlation of tumor-infiltrating T cells has been widely studied in breast cancer, that of tumor-infiltrating B cells and plasma cells has not received so much attention, especially in triple-negative breast cancer (TNBC). METHODS: We investigated 114 patients with TNBC who had surgery between 2006 and 2019 at Dokkyo Medical University Hospital. Intratumoral (i) TILs were considered to be lymphocytes within cancer cell nests and directly infiltrating tumor cells. Similarly, stromal (s) TILs were considered to be lymphocytes within the tumor stroma, but not directly infiltrating tumor cells. CD20 + , CD38 + and CD138 + staining was determined by estimating the number of positive B cells. RESULTS: sCD20 + TILs had prognostic significance for relapse-free survival (RFS) (p = 0.043) and overall survival (OS) (p = 0.027). The sCD38 + TILs were significantly related to favorable RFS (p = 0.042). iCD38, iCD138, and sCD138 was not significantly correlated with RFS (p = 0.065, p = 0.719, p = 0.074) or OS (p = 0.071, p = 0.689, p = 0.082). CONCLUSIONS: The present study demonstrated that a high density of sCD20 + TILs was significantly related to favorable prognosis in both RFS and OS. Increased sCD38 + TILs in TNBC were correlated with a significantly favorable prognosis in RFS. These results indicate that TILs-B may have a profound influence on the clinical outcome of TNBC.

Invasive mole with lung metastasis after an abdominal complete hydatidiform mole treatment.

A 27-year-old woman, gravida 1, para 0, was transferred to our hospital with acute abdominal pain. Her serum human chorionic gonadotropin level was 60 231 mIU/mL. Transabdominal ultrasound revealed an echo-free space, and emergency laparoscopy-assisted surgery was performed with a preoperative diagnosis of ruptured ectopic pregnancy. The pelvic cavity was filled with clots, and the peritoneal surface of the uterine fundus was swollen and showed continuous bleeding. The lesion was located on peritoneum and not connected with the uterine cavity. Histological examination of the conceptus showed features of a complete hydatidiform mole. After a mild decrease, hCG levels adversely increased 3 weeks later with multiple lung nodules. With a diagnosis of invasive moles, the patient was administered chemotherapy. This case demonstrates that it is important to recognize the potential of ectopic hydatidiform moles through abdominal pregnancy. This is the first report of an invasive abdominal hydatidiform mole, and hCG monitoring seemed to be essential for gestational trophoblastic neoplasia detection.

Histopathological evaluation of the effectiveness of oral Eppikajutsuto treatment for lymphatic malformation.

BACKGROUND: Lymphatic malformation (LM) is a congenital disease caused by lymphatic vessel malformation. Although standard therapies for LMs are sclerotherapy and/or surgical excision, a new therapy using Japanese herbal medicine Eppikajutsuto (TJ-28) has been recently reported as clinically effective. We aimed to experimentally confirm the therapeutic effectiveness of TJ-28 for LMs. METHODS: LM lesions were generated in the mesentery and peritoneum of mice by intraperitoneal injection of Freund's incomplete adjuvant. Mice with LMs were treated by gavage or dietary administration of TJ-28 for 2 months. Formalin-fixed paraffin-embedded tissue sections of mesentery and peritoneum tissues were histologically and immunohistochemically examined by focusing on lymph nodes and perinodal lymph vessels. RESULTS: Multiple Freund's incomplete adjuvant-associated foreign-body granulomas were formed in the mesentery and peritoneum, resulting in congestion of lymph fluid and dilatation of lymph vessels. The numbers and sizes of lymph nodes were not significantly different between TJ-28-treated and control groups. However, the luminal areas of lymphatic vessels were reduced significantly in the TJ-28 treatment group by both gavage and dietary administrations. CONCLUSION: TJ-28 conspicuously reduced congestion of lymph fluid. This is the first histopathological evaluation of LM model mice to study the effectiveness of oral TJ-28 treatment.

CD68- and CD163-positive tumor-associated macrophages in triple negative cancer of the breast.

Tumor-associated macrophages (TAMs) have recently been reported as an important factor in tumor growth and the progression of cancer. The prognostic significance of localizations and densities of TAMs in triple negative cancer (TNC) of the breast is not well understood. The aim of this study was to assess the localizations and densities of the TAMs subtype in TNC and examine their clinicopathological features. The study was based on 107 TNC cases operated on at Dokkyo Medical University Hospital using the pan-macrophage marker CD68 and the M2 macrophage marker CD163 in the tumor stroma (TS) and tumor nest (TN), respectively, and examined the clinicopathological significance. Multivariate Cox regression analyses revealed that age and CD163+ TAMs in both the TS and TN were independent prognostic factors for relapse-free survival and overall survival. No correlation was found between the number of CD68+ cells or the CD163/CD68 ratio either in TS or TN, or clinicopathological features. Our study found that infiltration of CD163+ TAMs, rather than CD68+, in both TS and TN was associated with poor prognosis in TNC patients by multivariate analysis. This suggests that CD163+ TAMs may affect the prognosis of TNC by not only regulating the immune reaction by TAMs in TS, but also because of their direct influence on TN.

Prognostic impact of a tumor-infiltrating lymphocyte subtype in triple negative cancer of the breast.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have recently been reported as an important factor in the tumor microenvironment and influence the growth and progression of cancer. However, the relationship between immune cell subpopulations, such as CD4+, CD8+, and FOXP3+, in breast cancer, especially in triple negative carcinoma (TNC), remains unclear. METHODS: The subjects were 107 patients with TNC that were surgically resected at Dokkyo Medical University Hospital between 2006 and 2018. The expression of CD4+, CD8+, and FOXP3+ was evaluated in TILs and expressed as the numbers of positive cells. RESULTS: Univariate analysis revealed that the TILs were not prognostically significant. In multivariate analyses, increased infiltration of intratumoral (i) CD4+ TILs was found to have a good prognosis in relapse-free survival (RFS). In contrast, a high stromal CD8+ TILs level was found to be a favorable prognostic factor in RFS (p = 0.038) and overall survival (OS) (p = 0.046). A low sFOXP3 + TILs level was significantly associated with favorable RFS (p < 0.001) and OS (p = 0.029). CONCLUSIONS: The present study demonstrated no difference in TILs and survival in TNC. However, there was a significant correlation in prognosis with levels of iCD4+, sCD8+, and sFOXP3 + TILs in TNC. The difference in TNC clinical outcome may be due to the subtype of the infiltrating TILs.

Usefulness of imprint cytology of gonadoblastoma with dysgerminoma in a patient with Turner syndrome and a Y chromosome: A case report and literature review.

Ovarian gonadoblastoma coexisting with a dysgerminoma is extremely rare in patients with Turner syndrome (TS) and a Y chromosome. The cytological findings, including imprint cytology, of these unusual ovarian tumors have rarely been reported. We report a rare patient with a gonadoblastoma with dysgerminoma, 3.0 × 2.0 cm in size; she was a 19-year-old woman with TS and a Y chromosome. She underwent laparoscopic bilateral gonadectomy, and the tumor was classified as stage IA (pT1aNxM0) according to the International Federation of Gynecology and Obstetrics classification system. Intraoperative imprint cytology revealed two types of neoplastic cells: small tumor cells surrounding light green-stained or eosinophilic hyaline globules with marked calcification, suspicious for gonadoblastoma; and large, round, atypical cells with abundant cytoplasm, macronucleoli, and marked lymphocytic infiltration (two-cell pattern), suspicious for dysgerminoma. The cytology results in our patient may represent the second reported results of imprint cytology describing a gonadoblastoma with dysgerminoma. They are the first reported results in a patient with TS and a Y chromosome.

A rare case of pulmonary lepidic metastasis in patient with branch-type intraductal papillary mucinous carcinoma of the pancreas.

Pulmonary lepidic metastasis from intraductal papillary mucinous carcinoma (IPMC) of the pancreas is extremely rare. The patient was a 50s-year old male who was hospitalized in the department of respiratory in our hospital for the evaluation of ground-glass opacities in both lungs on computed tomography (CT) imaging. Steroid therapy was administered, as interstitial pneumonia was suggested; however, there was no improvement. A transbronchial lung biopsy (TBLB) revealed the possibility of distant lung metastases. Abdominal CT revealed pancreatic cystic lesions; the patient was, therefore, referred to our department for further evaluation. Endoscopic ultrasound revealed large multi-cystic lesion with mural nodule and wall thickness. A subsequent pancreatic juice cytology under endoscopic retrograde cholangiopancreatography revealed adenocarcinoma. As this was consistent with the pathological findings shown on TBLB, IPMC metastasis to the lung was diagnosed. In this case, it was considered that pulmonary lepidic metastasis from IPMC by CT imaging and pathological findings. Although the cases of pulmonary lepidic metastasis from gastrointestinal cancer are rare, we should consider these pathological conditions when pneumonia-like infiltration observed on imaging studies does not respond to treatment.

Oestrogen receptor-negative/progesterone receptor-positive phenotype of invasive breast carcinoma in Japan: re-evaluated using immunohistochemical staining.

BACKGROUND: The existence of progesterone receptor (PgR) expression in oestrogen receptor (ER)-negative breast carcinoma is controversial. Here, we re-evaluated ER-negative/PgR-positive (ER-/PgR+) carcinoma cases by immunohistochemical staining (IHC). MATERIALS AND METHODS: We selected patients who underwent surgery for primary breast carcinoma from our databases at Dokkyo Medical University Hospital and Kameda General Hospital. Among the 9844 patients, the largest series in Japan, 27 (0.3%) were initially diagnosed as ER-/PgR+ breast carcinomas and we re-evaluated by IHC. RESULTS: The re-evaluated IHC showed that of the 27 patients with the initial results of ER-/PgR+, 12 were ER+/PgR+, 8 were ER-/PgR-, and 7 were ER-/PgR+. ER was negative in 12 of 27 patients (44.4%), and PgR was positive in 8 of 27 patients (29.6%). In our seven re-evaluated and confirmed as ER-/PgR+ cases, the staining proportions of tumor cells were 0% in ER and 1-69% (average 15.8%) in PgR. The average staining proportion of PgR in the re-evaluated ER-/PgR+ phenotype was lower than the initial diagnosis. Histological grading was as follows: grade I, one case; grade II, two cases; grade III, four cases. There were two lymph-node-positive cases. CONCLUSIONS: The ER-/PgR+ phenotype was confirmed after re-evaluation of ER and PgR assessment by a different pathologist. We recommend that pathologists discuss with clinicians, or re-test and re-evaluate ER/PgR expression, particularly in low-grade carcinoma and with a high staining proportion of PgR in the ER-/PgR+ phenotype.

Liposarcoma of the uterine corpus: A case report and literature review.

Liposarcoma of the uterine corpus is extremely rare. We performed a laparotomy on a 55-year-old woman with the complaints of abdominal distension and genital bleeding who was found to have a uterine tumor, 17 × 16 cm in diameter. The preoperative diagnosis was a lipoma or lipoleiomyoma of the uterine corpus. However, pathological examination revealed proliferation of mature adipocytes and lipoblast-like atypical cells with small, weakly pleomorphic nuclei and foamy or vacuolated cytoplasm present within a fibrous septum. Immunohistochemistry showed that the tumor cells were focally positive for mouse double minute 2 homolog (MDM2). The final pathological diagnosis was a well-differentiated liposarcoma of International Federation of Gynecology and Obstetrics (FIGO) stage IB (pT1bNxM0). On magnetic resonance imaging (MRI), T1 -weighted and fat-saturated images showed high and low intensity in the tumor, respectively, suggesting that this tumor contained a fat component. The septum inside the tumor had a contrast enhancement on T1-weighted, gadolinium-enhanced imaging. The septum was nonuniformly thickened and partially nodular. In hindsight, these findings may have suggested a well-differentiated liposarcoma in the uterine corpus rather than a lipoma or lipoleiomyoma. Clinicians should be aware of the possibility of a liposarcoma of the uterine corpus when a neoplasm contains adipose tissue and a nonuniformly thickened or partially nodular septum on MRI.

Nuclear Morphometry of Lung Squamous Cell Carcinomas in Cytologic Study.

BACKGROUND: The nuclei of most cancer cells in histopathologic preparations differ from normal nuclei and vary individually in size, shape, and chromatin pattern. Although the cytologic characteristics of squamous cell carcinoma (SCC) of the lung have been described, quantification of the cytologic features has not been established. METHODS: Cytologic investigations were performed on bronchial brushings or washings, or fine-needle aspirates. We analyzed the nuclear area (NA) of 50 tumor cells in 32 patients with SCC of the lung and 50 bronchial epithelial cells in 20 patients with no evidence of malignancy including inflammatory lesions. RESULTS: The NA of tumor cells (102.4 ± 26.2 µm2) was significantly larger than that of bronchial epithelial cells (64.1 ± 16.9 µm2) (P = 0.001). The receiver operating characteristic (ROC) curve analysis showed that an NA cutoff level of 86 µm2 had a sensitivity of 75% and specificity of 88% to detect malignant components. CONCLUSION: We conducted quantitative analyses of NA in SCC using cytologic specimen, NA was a useful parameter for evaluation of differential diagnosis between SCC and non-malignancies even in cytologic specimens.

Characteristic Histological Findings of Asymptomatic EBV-associated Lymphoproliferative Disorders in Tonsils.

Recently, an in situ hybridization (ISH) and immunohistochemical study demonstrated that Epstein-Barr virus (EBV) infection may be involved in tonsillar hypertrophy and recurrent tonsillitis in children and young adolescents. The present study was based on 630 consecutive specimens from tonsillectomies performed at the Dokkyo University School of Medicine between 2002 and May 2017. Clinical findings were obtained from hospital records. Histologically, a "pale clear zone" was characterized by hyperplastic germinal centers with ill-defined borders and interfollicular expansion. Immunohistologically, the majority of immunoblasts were CD20-positive, whereas medium to large lymphoid cells usually expressed CD3. Among 14 lesions, numerous EBV-encoded small RNA (EBER)-positive cells were detected in 10. In 7 of these 10 lesions, EBER-positive cells were detected in germinal centers as well as in the interfollicular area. Based on our results, the "pale clear zone" suggests asymptomatic EBV infection of the tonsil. The present study demonstrated that "pale clear zones" should be taken into consideration when diagnosing asymptomatic EBV-associated LPDs in the tonsils of children and young adolescents as well as in middle-aged patients.

Intraoperative frozen section diagnosis of bile duct margin for extrahepatic cholangiocarcinoma.

AIM: To evaluate the usefulness of frozen section diagnosis (FSD) of bile duct margins during surgery for extrahepatic cholangiocarcinoma (CCA). METHODS: We retrospectively analyzed 74 consecutive patients who underwent surgery for extrahepatic CCA from 2012 to 2017, during which FSD of bile duct margins was performed. They consisted of 40 distant and 34 perihilar CCAs (45 and 55 bile duct margins, respectively). The diagnosis was classified into three categories: negative, borderline (biliary intraepithelial neoplasia-1 and 2, and indefinite for neoplasia), or positive. FSD in the epithelial layer, subepithelial layer, and total layer was compared with corresponding permanent section diagnosis (PSD) postoperatively. Then, association between FSD and local recurrence was analyzed with special reference to borderline. RESULTS: Analysis of 100 duct margins revealed that concordance rate between FSD and PSD was 68.0% in the total layer, 69.0% in the epithelial layer, and 98.0% in the subepithelial layer. The extent of remaining biliary epithelium was comparable between FSD and PSD, and more than half of the margins lost > 50% of the entire epithelium, suggesting low quality of the samples. In FSD, the rate of negative margins decreased and that of borderline and positive margins increased according to the extent of the remaining epithelium. Diagnostic discordance between FSD and PSD was observed in 31 epithelial layers and two subepithelial layers. Alteration from borderline to negative was the most frequent (20 of the 31 epithelial layers). Patients with positive margin in the total and epithelial layers by FSD demonstrated a significantly worse local recurrence-free survival (RFS) compared with patients with borderline and negative margins, which revealed comparable local RFS. Patients with borderline and negative margins in the epithelial layer by PSD also revealed comparable local RFS. These results suggested that epithelial borderline might be regarded substantially as negative. When classifying the status of the epithelial layer either as negative or positive, concordance rates between FSD and PSD in the total, epithelial, and subepithelial layers were 95.0%, 93.0%, and 98.0%, respectively. CONCLUSION: During intraoperative assessment of bile duct margin, borderline in the epithelial layer can be substantially regarded as negative, under which condition FSD is comparable to PSD.

Clinicopathological study of a dimorphic variant of breast carcinoma.

BACKGROUND: Dimorphic cells have abundant clear cytoplasm similar to myoepithelial cells, and the nuclei are identical to those in adjacent malignant columnar epithelial cells. A dimorphic variant of a breast carcinoma involves a neoplastic proliferation of epithelial cells including dimorphic cells. METHODS: The subjects were patients with primary breast carcinoma, who underwent surgical resection at the Hospital of Dokkyo Medical University between 2000 and 2016, and were reviewed and diagnosed with a dimorphic variant of breast carcinoma. RESULTS: Dimorphic ICs typically showed a low-grade tumor and Hormonal receptor (HR) (estrogen and/or progesterone)+/HER2- subtype. Age, mean tumor size, status of nodal metastasis, stage and disease-free survival and overall survival did not differ between dimorphic and non-dimorphic ICs. The dimorphic cells were negative for p63 and cytokeratin 5/6 and 14 in most cases. In contrast, dimorphic cells were positive for HR, androgen receptor, and showed marked membrane-associated staining for E-cadherin and cytoplasmic staining for gross cystic disease fluid protein 15. CONCLUSIONS: The morphological features of dimorphic cells may be confused with cells of other origins if the features of the dimorphic cells are not recognized. However, the typical morphological architecture of this carcinoma and expression of immunohistochemical markers support the diagnosis.