Telepathology in intraoperative frozen section consultation of breast cancer sentinel node biopsy in Fukushima, Japan following the 2011 triple disaster: diagnostic accuracy and required time during the early implementation phase.

In breast cancer surgery, some medical facilities lack the necessary resources to conduct sentinel lymph node biopsy and its intraoperative frozen section consultation. In the coastal rural area of Fukushima, Japan, which has suffered from physician undersupply following the 2011 triple disaster of earthquake, tsunami and nuclear disaster, we explored the feasibility of telepathology by evaluating the diagnostic accuracy in remote intraoperative frozen section consultation of sentinel lymph node biopsy and its required time. Although examination time has room for improvement, telepathology can be one possible solution in resource-limited areas.

A case of discordant histology and expression of programmed death ligand 1 between primary tumor and brain metastases in adenosquamous carcinoma of the lung.

A patient presented with vomiting and gait disturbance. Investigation revealed a single cerebellar tumor and another tumor in the upper lobe of the left lung. Based on the severe vomiting and gait disturbance, we removed the cerebellar tumor first, achieving resolution of symptoms. The cerebellar tumor was pathologically diagnosed as metastatic lung adenocarcinoma. No other metastases were identified, including in the mediastinal lymph nodes. We therefore resected the primary lung tumor. On final pathological analysis, the tumor in the upper lobe of the left lung was diagnosed as adenosquamous carcinoma with no lymph node metastasis. PD-L1 expression was low in the primary lung adenosquamous carcinoma and high in the cerebellar metastasis. Furthermore, both tumors were KRASG12C -positive. Tumor PD-L1 expression is considered important for immune escape. In this case, adenocarcinoma cells in the primary adenosquamous carcinoma may have migrated to form a cerebellar metastasis. In advanced lung cancer, tumor growth may be observed in some lesions even when many other lesions are controlled by chemo- or immunotherapy. Biopsy to confirm histology and PD-L1 expression is worth considering, depending on the location of the metastases and the invasiveness of the biopsy procedure.

Efficacy of selective transarterial chemoembolization for recurred liver metastases from intracranial meningioma: A case report.

Extracranial metastases from intracranial meningioma involve multiple organs with repeatedly recurrence. Due to the rarity of these metastases, management remains to be established, especially in cases that are not amenable to surgery, such as postsurgical relapse and multiple metastases. We present the case of a right tentorial meningioma with multiple extracranial metastases, including postsurgical recurrent liver metastases. The intracranial meningioma was surgically resected when the patient was 53 years of age. The patient was 66 years of age when the hepatic lesion was first revealed, for which an extended right posterior sectionectomy was performed. Histopathology demonstrated a metastatic meningioma. Twelve months after liver resection, multiple local recurrences in the right hepatic lobe were revealed. Because additional surgical resection would put the patient at risk of declining residual liver function, we performed selective transarterial chemoembolization, resulting in a reduction in size and good control without relapse. Selective transarterial chemoembolization for incurable liver metastatic meningiomas could be valuable in palliating patients unsuitable for surgery.

SPON1 is an independent prognostic biomarker for ovarian cancer.

BACKGROUND: Ovarian cancer has the worst outcome among gynecological malignancies; therefore, biomarkers that could contribute to the early diagnosis and/or prognosis prediction are urgently required. In the present study, we focused on the secreted protein spondin-1 (SPON1) and clarified the prognostic relevance in ovarian cancer. METHODS: We developed a monoclonal antibody (mAb) that selectively recognizes SPON1. Using this specific mAb, we determined the expression of SPON1 protein in the normal ovary, serous tubal intraepithelial carcinoma (STIC), and ovarian cancer tissues, as well as in various normal adult tissues by immunohistochemistry, and verified its clinicopathological significance in ovarian cancer. RESULTS: The normal ovarian tissue was barely positive for SPON1, and no immunoreactive signals were detected in other healthy tissues examined, which was in good agreement with data obtained from gene expression databases. By contrast, upon semi-quantification, 22 of 242 ovarian cancer cases (9.1%) exhibited high SPON1 expression, whereas 64 (26.4%), 87 (36.0%), and 69 (28.5%) cases, which were designated as SPON1-low, possessed the moderate, weak, and negative SPON1 expression, respectively. The STIC tissues also possessed SPON1-positive signals. The 5-year recurrence-free survival (RFS) rate in the SPON1-high group (13.6%) was significantly lower than that in the SPON1-low group (51.2%). In addition, high SPON1 expression was significantly associated with several clinicopathological variables. Multivariable analysis revealed that high SPON1 was an independent prognostic factor for RFS of ovarian cancer. CONCLUSIONS: SPON1 represents a prognostic biomarker for ovarian cancer, and the anti-SPON1 mAb could be valuable as an outcome predictor.

Ovarian strumal carcinoid: a case report.

BACKGROUND: Carcinoid tumors of the ovary are rare tumors, histopathologically classified as monodermal teratomas and somatic-type tumors arising from dermoid cysts. Their malignancy varies from borderline to malignant. Carcinoid tumors can occur in young and elderly women, and are sometimes seen in mature teratoma, struma ovarii, or mucinous cystadenoma as a nodule or tumor. Strumal carcinoid and mucinous carcinoid present as special types of carcinoid tumors of the ovary. CASE REPORT: This report describes a 56-year-old woman who presented with a large pelvic mass on abdominal ultrasonography during a medical examination. The diameter of the pelvic tumor was approximately 11 cm and was suspected to be ovarian cancer. The values of CA125 and CEA were above their reference intervals on preoperative examination. Abdominal total hysterectomy and bilateral salpingo-oophorectomy were performed. Intraoperative frozen-section histopathology suggested a diagnosis of mucinous adenocarcinoma; therefore, partial omentectomy and pelvic lymphadenectomy were also performed. Permanent-section histopathology led to a final diagnosis of strumal carcinoid of the ovary, stage IA (FIGO 2014). Six years post-operation, the patient had no sign of recurrence.

A case of strongly suspected Lynch syndrome with colorectal neuroendocrine carcinoma.

BACKGROUND: Neuroendocrine cell carcinomas (NEC) of the colon and rectum are uncommon, representing ~ 0.1% of all colorectal carcinomas. They are associated with a much worse prognosis compared to adenocarcinoma of the colon and rectum, as death occurs in approximately half of all patients within 1 year. Lynch syndrome (LS) is the most common cause of inherited colorectal cancer, accounting for 2-4% of newly diagnosed colorectal cancer cases. This case is extremely rare which was strongly suspected LS as the background, and NEC as the histological type of colorectal cancer. CASE PRESENTATION: The patient was a 44-year-old man presenting with vomiting as the main complaint. He had undergone ileocecal resection for cecal cancer at age 29. The diagnosis was obstructive descending colorectal cancer, and colonoscopy revealed tumors in the rectum and sigmoid colon in addition. Due to multiple occurrences of colorectal cancer and its prevalence in the patient's family, LS was suspected. The operation which was a subtotal proctocolectomy was performed. Pathological analysis revealed complete curative resection and the descending colon cancer of the obstructed portion was at the most advanced pathological Stage IIIC in UICC TNM classification, and the tissue type was a NEC. The Ki-67 index was 70%. The results of the microsatellite instability (MSI) test showed high-frequency MSI. The BRAF V600E variant was negative. The immunoexpression of MLH1 was positive, MSH2 was negative, PMS2 was positive, and MSH6 was negative. CONCLUSIONS: Extended surgery is recommended for incipient colorectal cancer in LS cases in order to reliably reduce the risk of developing metachronous colorectal cancer. The survival outcome of surgery alone on digestive tract NECs, even locoregional lesions that are completely resection, is extremely poor. It is currently unclear if digestive tract NECs develop more readily in patients with LS. The accumulation of additional cases is necessary.

Malignant rhabdoid tumours of the small intestine with multiple organ involvement: Case report.

INTRODUCTION AND IMPORTANCE: Malignant rhabdoid tumours (MRTs) were first described as an infrequent variant of Wilms' tumour and have been reported in several organs. The small intestine is a rare site for MRTs. CASE PRESENTATION: A 70-year-old man presented with appetite loss and melena. Haemorrhagic small intestinal tumours, swollen mesenteric and paraaortic lymph nodes, a tumour in the left kidney, and multiple tumours in the lung were found. He underwent partial resection of two haemorrhagic small intestinal tumours classified as MRTs based on the results of a pathological examination. However, melena appeared again on postoperative day 6. We performed another operation and resected approximately 180 cm of the small intestine that contained multiple tumours. All lesions were classified as MRTs. Unfortunately, melena appeared again 4 days after the second operation. He did not want invasive therapy and died from massive melena 2 months after the initial surgery. CLINICAL DISCUSSION: MRTs of the small intestine are uncommon and have an extremely poor prognosis. Although curative resection is an important treatment, cases of metastasis at diagnosis and postoperative early recurrence have been observed, as was the case for the patient described herein. In these cases, effective systemic therapy is necessary. Recently, tumour suppressor genes were shown to be involved in the occurrence of MRT, and new therapies for MRT have been studied. CONCLUSION: We herein conclude effective systemic therapy is necessary for MRTs with multiple organ involvement. The development of new drugs for this disease is ongoing.

Incidental early lung adenocarcinoma after surgery for catamenial pneumothorax.

A 40-year-old female patient underwent surgery at our hospital for recurrent pneumothorax. A defect on the right diaphragm was diagnosed as ectopic endometriosis. However, air leakage continued 2 days after surgery. Chest computed tomography identified a 5-mm ground glass opacity in the right S3 field, suggestive of lung cancer. Ten days after the initial surgery, she underwent curative surgery for both pneumothorax and the lung tumor. The tumor was diagnosed as bronchioloalveolar carcinoma, but no other endometriosis was identified. The patient has remained well with no recurrence of lung cancer or pneumothorax since the second surgery.

Granulomatous lymphadenitis.

In this review, representative types of granulomatous lymphadenitis (GLA) are described. GLA can be classified as noninfectious GLA and infectious GLA. Noninfectious GLA includes sarcoidosis and sarcoid-like reaction. The cause of sarcoidosis remains unknown, but it has good prognosis. Sarcoid-like reaction, which is considered to be a biological defense mechanism, is observed in regional lymph nodes with many underlying diseases. Infectious GLA can be classified as suppurative lymphadenitis (LA) and nonsuppurative LA. Suppurative LA generally shows follicular hyperplasia and sinus histiocytosis in the early phase. In tularemia and cat scratch disease, monocytoid B lymphocytes (MBLs) with T cells and macrophages contribute to the formation of granuloma. However, none of the epithelioid cell granulomas of Yersinia LA contains MBLs like in cat scratch disease. In addition, almost all have a central abscess in granulomas induced by Gram-negative bacteria. In terms of the lymph nodes, tularemia and cat scratch disease are apt to affect the axillary and cervical regions while Yersinia LA affects the mesenteric lymph node. Nonsuppurative LA includes tuberculosis and BCG-histiocytosis. These are induced by delayed allergic reaction of M. tuberculosis. Tuberculosis LA mainly appears in the cervical lymph node. Organisms are histologically detected by Ziehl-Neelsen staining in the necrotic area. Toxoplasmosis is also a nonsuppurative protozoan infection (Toxoplasma gondii). In toxoplasma LA, MBLs can also be seen, but round and organized, well-formed granulomas are not found in this disease. Furthermore, necrosis is not induced and there are no accompanying neutrophils, eosinophils and fibrosis. GLA described above is associated with characteristic histological findings. An accurate pathological diagnosis using the above findings can lead to precise treatment.

Temporal differences of onset between primary skin lesions and regional lymph node lesions for tularemia in Japan: a clinicopathologic and immunohistochemical study of 19 skin cases and 54 lymph node cases.

For tularemia, a zoonosis caused by the gram-negative coccobacillus Francisella tularensis, research of the relation between skin lesions and lymph node lesions has not been reported in the literature. This report describes skin lesions and lymph node lesions and their mutual relation over time for tularemia in Japan. Around the second day after infection (DAI), a subcutaneous abscess was observed (abscess form). Hand and finger skin ulcers formed during the second to the fourth week. Subcutaneous and dermal granulomas were observed with adjacent monocytoid B lymphocytes (MBLs) (abscess-granulomatous form). From the sixth week, large granulomas with central homogeneous lesions emerged diffusely (granulomatous form). On 2-14 DAI, F. tularensis antigen in skin lesions was detected in abscesses. During 7-12 DAI, abscesses with adjacent MBLs appeared without epithelioid granuloma (abscess form) in regional lymph nodes. During the second to fifth week, granulomas appeared with necrosis (abscess-granulomatous form). After the sixth week, large granulomas with a central homogeneous lesion (granulomatous form) appeared. F. tularensis antigen in lymph node lesions was observed in the abscess on 7-92 DAI. Apparently, F. tularensis penetrates the finger skin immediately after contact with infected hares. Subsequently, the primary lesion gradually transfers from skin to regional lymph nodes. The regional lymph node lesions induced by skin lesion are designated as dermatopathic lymphadenopathy. This study revealed temporal differences of onset among the skin and lymph node lesions.

Extracranial metastasis of anaplastic oligodendroglioma with 1p19q loss of heterozygosity--case report.

We report a rare case of anaplastic oligodendroglioma with extracranial metastasis, showing 1p19q co-deletion in both the brain tissue and the metastatic site. A 53-year-old man first presented with a left frontal tumor. The tumor was subtotally removed and irradiation was performed for the residual tumor and tumor bed. Two years after the initial treatment, several tumors appeared on his neck and one was resected. Histological examination revealed anaplastic oligodendroglioma, proved to be the same as the previous brain tumor. The patient refused further treatment, and died 30 months after the initial treatment. Autopsy demonstrated multiple extracranial metastases in the vertebrae, lymph nodes, spinal dura mater, thymus gland, and chest wall. We confirmed 1p19q loss of heterozygosity in both lesions, suggesting that 1p19q co-deletion might important to extracranial metastasis of oligodendroglioma.

Up-regulated expression of ADAM17 in gastrointestinal stromal tumors: coexpression with EGFR and EGFR ligands.

Metalloproteinase activities of a disintegrin and metalloproteinases (ADAMs), matrix metalloproteinases (MMPs), and membrane type (MT-)MMPs are involved in many aspects of tumor biology. ADAMs are transmembrane proteins that cleave membrane-anchored proteins to release soluble factors, and thereby mediate important biological phenomena in tumors. The aim of this study was to analyze histopathology, expression and roles of metalloproteinases, especially ADAMs, in gastric gastrointestinal stromal tumor (GIST). Histopathology and immunohistochemical expression of ADAMs were examined in 89 gastric GISTs. In 11 GISTs, ADAM expression was examined at mRNA and protein levels by reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting, respectively. RT-PCR analysis showed frequent expression of ADAM9 (91%), ADAM10 (64%), ADAM17 (82%), MMP-2 (82%), and MT1-MMP (73%). However, ADAM17 and MMP-2 were the only metalloproteinases that were up-regulated in GISTs at the protein level compared with non-neoplastic gastric tissues. ADAM17 was immunohistochemically expressed in 93% of GIST versus 16% of normal gastric tissues. Furthermore, CD117-positive interstitial cells of Cajal in normal gastric tissues were all negative for ADAM17 with double immunostaining. Expressions of epidermal growth factor receptor (EGFR) and several EGFR ligands such as amphiregulin, heparin-binding epidermal growth factor (HB-EGF), betacellulin, and epiregulin were also demonstrated in GIST by RT-PCR. Protein expression of EGFR, phosphorylated EGFR, amphiregulin, and HB-EGF, both of which can be shed by ADAM17, was confirmed in tumors coexpressing ADAM17 by immunoblotting. Moreover, proteolytically cleaved soluble forms of amphiregulin were identified in tumor extracts. Considered together, the results suggest that ADAM17 may contribute to the progression and growth of GIST through shedding of EGFR ligands and consequent EGFR stimulation. ADAM17, as a major sheddase in GIST, could be potentially a suitable target in anticancer treatment of imatinib-resistant GISTs.

[Two cases of primary unresectable and/or recurrent gastrointestinal stromal tumors of small intestine presenting hemoperitoneum caused by administration of imatinib mesylate].

Case1 was a 52-year-old man who had recurrence of postoperative intra-abdominal disseminations from gastrointestinal stromal tumor (GIST) of the jejunum. Case2 was a 66-year-old man who had GIST of the jejunum with multiple liver metastases. Two cases presented hemoperitoneum caused by administration of imatinib mesylate, and we conducted emergent surgery. In spite of surgically non-curative cases, it is suggested that the surgical management for GIST of high grade group with peritoneal exposure should be followed by the administration of imatinib mesylate.

Histological diversity of reactive and atypical proliferative lymph node lesions in systemic lupus erythematosus patients.

Localized or generalized lymphadenopathy, which may be associated with systemic symptoms such as fever, is frequently found in patients with systemic lupus erythematosus (SLE). Histologically, the lymph node lesion is characterized by varying degrees of coagulative necrosis with hematoxylin bodies or reactive follicular hyperplasia. The former histology is unique to SLE, but is rarely seen in biopsied specimens. In this review, we describe a histologic variation of SLE lymphadenopathy based on the findings of our own cases, and discuss several problems related to the differential diagnosis of various benign and malignant lymphoproliferative disorders (LPDs). Among 33 cases we encountered, 17 (51%) cases exhibited atypical LPDs: (i) reactive follicular hyperplasia with giant follicles (RFHGFs), 3 cases; (ii) histologic findings of Castleman's disease (CD), 5 cases ; (iii) atypical paracortical hyperplasia with lymphoid follicles (APHLFs), 7 cases; and (iv) atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP), 2 cases. This finding indicates that atypical LPDs frequently appear in SLE. Moreover, the majority of patients with atypical LPDs exhibited follicular hyperplasia (RFHGF, 3 cases; histologic findings of CD, 5 cases; and APHLF, 7 cases). Previously, follicular hyperplasia was usually considered a non-specific change and therefore has received little attention in the literature. However, the present review indicates that reactive follicular hyperplasia in lymph nodes from SLE occasionally poses serious problems in the differential diagnosis of various benign and malignant LPDs. The presence of numerous copies of Epstein-Barr virus was determined by in situ hybridization studies in only two (8%) of the 26 cases examined. As previously suggested, the absence of EBV, as determined by ISH studies, in the majority of LPDs associated with SLE indicates that EBV is not related to the lymphoproliferative process, and suggests that the underlying cause of the patient's lymphadenopathy may reside in the immune deficit of SLE in the majority of reactive and atypical LPDs associated with SLE.

lmmunoelectron microscopic examination of cord blood CD5+ B cells.

In this study, we have categorized cord blood CD5(+) B cells, which were examined using the horseradish peroxidase-colloidal gold double labeling immunoelectron microscopy, into three subtypes based on their morphology and immunohistochemical characteristics. Type 1a cells and type 1b cells (9% and 17% of the CD5(+) B cells, respectively) had few cytoplasmic organelles, a high nuclear/cytoplasmic (N/C) ratio (0.66 +/- 0.03 and 0.58 +/- 0.04, respectively), and a low nuclear contour index (NCI) value (1.56 +/- 0.30 and 1.50 +/- 0.27, respectively), whereas type 2 cells (74% of the CD5(+) B cells) had a low N/C ratio (0.44 +/- 0.11) and a high NCI value (2.05 +/- 0.68). Type 2 cells, which had many cytoplasmic organelles, frequently had several uropod-like processes that bound to the gold particles. The N/C ratios clearly showed that there were significant differences among the three types of CD5(+) B cells (p < 0.01), and between CD5(+) T cells and the three types of CD5(+) B cells (p < 0.05). For the NCI values, only type 1b and type 2 cells showed a significant difference (p < 0.05). These findings suggest that type 1a cells are transformed into type 1b cells, and then into type 2 cells.

Ewing's sarcoma in the spinal nerve root: a case report and review of the literature.

Ewing's sarcoma (ES) is a highly malignant tumor composed of uniform small round cells. Recently, a single biologic entity, Ewing's sarcoma family of tumors (ESFT) has been accepted. The entity includes ES, extraskeletal Ewing's sarcoma (EES) and primitive neuroectodermal tumor (PNET). ESFT cells have immunoreactivity for CD99, an antigen determined by the MIC2 gene. Most ESFT has the (11;22) (q24;q12) translocation. The translocation results in the fusion of the EWS gene with the transcription factor gene FLI1 which has been considered a hallmark of ESFT. We present an extremely unusual case with ESFT in a spinal nerve root mimicking a neurogenic dumbbell tumor. A male aged 20 years noticed pain in his right buttock. Magnetic resonance imaging (MRI) revealed a mass in the right L5/S intervertebral foramen and the lesions in the sacrum. Surgery was performed with a presumptive diagnosis of a nerve sheath tumor. At surgery, the tumor was located in the right L5 nerve root sleeve. The sacral lesions were observed closely. At one month after surgery, radiologically multiple lesions were detected in the pelvic bones. Microscopically the lesions from the root and ilium were composed of small round cells immunoreactive for CD99. Reverse transcription-polymerase chain reaction detected transcripts resulting from the fusion of the EWS gene with FLI1 genes in the iliac lesion. Immunoreactivity for CD99 and detection of the EWS-FLI1 hybrid transcripts are important for the correct diagnosis of ESFT arising in an unusual location.

Hepatocyte growth factor and c-Met immunoreactivity are associated with metastasis in high grade salivary gland carcinoma.

Interactions between hepatocyte growth factor (HGF) and its receptor, c-Met, have been associated with invasion, metastasis and carcinogenesis in in vitro experiments. We investigated the relationship between HGF/c-Met immunoreactivity and the clinical features of 33 patients with high grade salivary gland carcinomas. c-Met and stromal HGF (expression of HGF in fibroblasts adjacent to tumor nests) were found to significantly correlate with regional lymph node and distant metastasis (p<0.05), but not with HGF expression, in tumor cells. Stromal HGF was also found to correlate with tumor size (p<0.05). In addition, a significant correlation between c-Met and stromal HGF expression (p<0.0001) was observed. Overall survival in patients with c-Met and stromal HGF immunoreactivity was significantly worse than in patients without c-Met and stromal HGF immunoreactivity (p=0.0002). The present findings suggest that HGF may bind to c-Met in a paracrine fashion, thereby enabling metastasis of high grade salivary gland carcinomas. Thus, HGF/c-Met immunoreactivity might be associated with a poor prognosis in patients with high grade salivary gland carcinomas.

Association of hepatocyte growth factor expression with salivary gland tumor differentiation.

To clarify the significance of hepatocyte growth factor (HGF) expression in salivary gland tumors, HGF distribution in tissue sections and HGF concentrations in saliva and serum were examined. Sixty salivary gland adenomas, 61 salivary gland carcinomas and three autopsy fetuses were studied. Hepatocyte growth factor expression was observed in the duct-type luminal cells by immunohistochemical staining and in situ hybridization. However, HGF failed to be expressed in acinar cells and myoepithelium of normal salivary gland tissue. Hepatocyte growth factor tended to be expressed more intensely in benign salivary gland tumors than in malignant salivary gland tumors (P < 0.0001). In highly malignant tumors, the expression was limited in some cases. Salivary and serological HGF concentrations of 18 patients, comprised of 12 benign cases and six malignant cases, were analyzed before and after operation by an ELISA system. The concentrations were distinctly elevated after operation, in both saliva and serum, compared to before operation (P < 0.0005). However, there were no significant relationships between HGF concentration and histology, age, gender, size or location. Our findings suggest that HGF may play an important role in the development of salivary ducts of normal salivary tissues and differentiation of ductal structures of their neoplasms, while HGF kinetics in saliva and serum would be less likely to reflect the neoplastic character, benign or malignant.

A case of lymphoepithelioma-like carcinoma arising from the palatine tonsil.

Lymphoepithelioma is the designation that has been given to describe undifferentiated squamous cell carcinoma variants of nasopharyngeal neoplasms (World Health Organization type 3), and a strong association with Epstein-Barr virus (EBV) infection has been established. Outside the nasopharynx, lymphoepithelioma-like carcinomas (LEC) are exceedingly rare in other head and neck lesions. This report features a rare case of LEC of the palatine tonsil occurring in a 60-year-old Japanese man who presented with a three-month history of a neck mass. The surface of tonsils were smooth, not ulcerated macroscopically, and the ipsilateral tonsil showed only slight enlargement on radiological findings. Diagnosis of lymphoepithelioma was finally made based on the pathological review of the tonsillectomy specimens, preceded by a cervical lymph node biopsy. The patient was treated with irradiation and adjuvant chemotherapy. RNA in situ hybridization as well as polymerase chain reaction (PCR) techniques, and serological testing did not demonstrate an association with EBV infection. The clinical presentation, pathological features and association with EBV are described with a review of the literature.