High platelet-to-lymphocyte ratios in triple-negative breast cancer associates with immunosuppressive status of TILs.

BACKGROUND: Rating lymphocytes (TILs) are a prognostic marker in breast cancer and high TIL infiltration correlates with better patient outcomes. Meanwhile, parameters involving immune cells in peripheral blood have also been established as prognostic markers. High platelet-to-lymphocyte ratios (PLRs) and neutrophil-to-lymphocyte ratios (NLRs) are related to poor outcomes in breast cancer, but their mechanisms remain unknown. To date, TILs and these parameters have been examined separately. METHODS: We investigated the relationship between TILs and the peripheral blood markers, PLR and NLR, in the same patients, using surgical specimens from 502 patients with invasive breast carcinoma without preoperative chemotherapy. For analysis of triple-negative breast cancer (TNBC) patient outcomes, 59 patients who received preoperative chemotherapy were also examined. For immune cell profiling, multiplexed fluorescent immunohistochemistry (mfIHC) of CD3, CD4, CD8, FOXP3 and T-bet, was conducted. RESULTS: A positive correlation between PLR and TIL was observed in TNBC (P = 0.013). On mfIHC, tumors in patients with high PLR and NLR contained more CD3+CD4+FOXP3+ T-cells (P = 0.049 and 0.019, respectively), while no trend was observed in CD8+ T-cells. TNBC patients had different patterns of outcomes according to TIL and PLR, with the TIL-high/PLR-low group having the lowest rate of disease relapse and death, and the longest distant metastasis-free and overall survivals, while the TIL-low/PLR-high group had the shortest survivals. CONCLUSIONS: Our data suggest that the combination of PLR with TIL assessment may enable more accurate prediction of patient outcomes with TNBC.

Intraosseous Lipoma of the Calvaria in the Early Stage Resembling Normal Fatty Marrow.

Intraosseous lipoma (IOL) is a benign bone tumor that usually arises from the lower limb and rarely arises from the skull. Radiological diagnosis of a typical case is not problematic due to its characteristic calcification and marginal sclerosis. Here, we report a case of calvarial IOL in the early stage lacking conventional radiopathological features. The patient is a 7-year-old girl who presented with a slow-growing protuberance on the vertex of the head. Computed tomography displayed a low-density mass without calcification that was continuous with the surrounding diploe. The mass was resected piece by piece for diagnostic and cosmetic reasons. Histologically, the specimen consisted of bony trabeculae and intertrabecular adipose tissue, which resembled normal fatty marrow. However, adipose tissue was considered neoplastic since it lacked hematopoietic elements. The final diagnosis of IOL was made by radiopathological correlation. This case suggests that IOL should be included in the differential diagnosis of diploic expansion, even if calcification is absent. The histology of an early-stage IOL resembles normal fatty marrow, but recognizing the absence of hematopoietic elements aids the diagnosis. Also, our literature review indicates that such cases are likely to be encountered in the calvaria than cranial base.

Pretreatment tumour immune microenvironment predicts clinical response and prognosis of muscle-invasive bladder cancer in the neoadjuvant chemotherapy setting.

BACKGROUND: We examined the relationship between the tumour microenvironment and the clinical efficacy of neoadjuvant chemotherapy in patients with cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. METHODS: The study retrospectively evaluated 51 patients who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. Patients were divided into responders (

Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Tumour-infiltrating lymphocyte (TIL)-high breast tumours have a high rate of pathological complete response (pCR) with neoadjuvant chemotherapy. In our routine pathological diagnoses of biopsy specimens from pCR cases, we have observed a high infiltration of plasma cells (PCs). A positive correlation of PCs with favourable patient outcome has recently been reported, but little is known about how PCs contribute to local tumour immunity. METHODS: We retrospectively examined biopsy specimens from 146 patients with invasive breast cancer who received neoadjuvant chemotherapy. CD138+ PC infiltration was assessed by immunohistochemistry. Multiplexed fluorescent immunohistochemistry (mfIHC) with T and B cell markers was also conducted to elucidate the profile of immune cells. RESULTS: Greater PC infiltration was observed in the pCR group (p = 0.028) and this trend was confirmed in another patient cohort. With mfIHC, we observed significantly more CD8+, T-bet+CD4+, and CD8+FOXP3+ T cells, total B cells and PCs in pCR cases. Such cases were also characterised by high expression of both PD-1 and PD-L1 on B cells and PCs. In patients with hormone receptor-negative tumours, high PC infiltration was correlated with significantly longer disease-free survival (p = 0.034). CONCLUSIONS: We found that higher PC infiltration in biopsy specimens before neoadjuvant chemotherapy was associated with pCR. With mfIHC, we also revealed that the local cytotoxic immune response was clearly enhanced in pCR cases, as was the infiltration of B cells including PCs. Moreover, higher PC levels were correlated with favourable outcomes in hormone receptor-negative breast cancer patients.

A collision tumor of solitary fibrous tumor/hemangiopericytoma and meningioma: A case report with literature review.

An intracranial collision tumor is a rare lesion composed of two histologically different neoplasms in the same anatomic location. Even more rare is the collision tumor of a solitary fibrous tumor/hemangiopericytoma (SFT/HPC) and meningioma. The patient was a 46-year-old woman who had a 40 × 35 × 30-mm mass in the vermis of the cerebellum. Histologically, the mass consisted of two different components. One component showed the morphology of meningioma (World Health Organization (WHO) grade I), and the other component exhibited small round cell proliferation with hypercellular density, which was revealed to be SFT/HPC (WHO grade III) based on STAT6 immunohistochemistry. STAT6 showed completely different immunohistochemistry results in these two components (nuclear-negative in meningioma and nuclear-positive in SFT/HPC). Since these two neoplasms are associated with different prognoses, they should be distinguished from each other. When meningioma and an SFT/HPC-like lesion are identified morphologically, it is important to recognize the presence of such a collision tumor composed of meningioma and SFT/HPC, and identify the SFT/HPC component by employing STAT6 immunohistochemistry.

Hydrocele of the Canal of Nuck with Endometriosis: Right-Side Dominance Confirmed by Literature Review and Statistical Analysis.

Introduction. The canal of Nuck is an embryological remnant of the peritoneal pouch that extends into the labium majus of women. Hydrocele is the most common presentation, but only a small number of cases are reported in association with endometriosis. Case Presentation. The patient is a 45-year-old woman who presented with left inguinal mass with persistent pain. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a 30 mm cystic mass, and a hydrocele of the canal of Nuck (HCN) was suspected. The excised mass was a cyst containing yellow-tan serous fluid, and the cyst wall was lined by mesothelium. The morphology was consistent with conventional HCN. However, since several foci of endometrial-like epithelium and stroma were identified beneath the mesothelium, the mass was diagnosed with HCN with endometriosis (EM-HCN). Discussion. Right-side dominance of EM-HCN is suggested by several authors, but a thorough review has never been performed. For the first time, we reviewed the literature and statistically confirmed that EM-HCNs dominantly occur on the right side compared to those without endometriosis. We consider that this supports the theory that endometriosis derives from retrograde menstruation of endometrial tissue through fallopian tubes. When endometriosis is discovered in HCN, the clinician should be aware of the possibility of pelvic endometriosis.

High FOXA1 protein expression might predict late recurrence in patients with estrogen-positive and HER2-negative breast cancer.

BACKGROUND: Multi-gene expression assays have been developed with the aim of predicting late recurrence in patients with estrogen receptor (ER)-positive breast cancer. However, establishment of alternative markers based on immunohistochemistry is also important for achieving practical use. Based on our previous study, forkhead box A1 (FOXA1) protein was tested as a potentially useful predictive marker for late recurrence. METHODS: 117 patients with ER-positive HER2-negative invasive breast cancer who developed distant metastasis following curative surgery were retrospectively investigated. We also evaluated responsiveness to endocrine therapy according to FOXA1 expression. Furthermore, publicly available mRNA microarray data were analyzed to examine patterns of metastasis according to FOXA1 mRNA expression, employing the Kaplan-Meier plotter. RESULTS: High expression of FOXA1 was an independent factor predicting long disease-free survival (DFS), along with small tumor size (p = 0.010 and 0.016, respectively). Discrimination of DFS was improved by combining these two factors, i.e., patients with FOXA1-high small tumors had the longest DFS while those with FOXA1-low large tumors had the shortest DFS. Moreover, we revealed that risk of distant metastasis started to increase after the completion of adjuvant endocrine therapy in patients with FOXA1-high tumors. CONCLUSION: Among patients who developed distant metastasis, those with FOXA1-high tumors had significantly longer DFS. We believe our data to raise the possibility of FOXA1 being a useful predictive marker for late recurrence and to provide new insights into the biology of FOXA1-high breast cancers.

Coexistence of Cervical Leiomyosarcoma and Gastric-Type Adenocarcinoma In Situ with Extensive Extension to the Endometrium and Fallopian Tube.

Cervical leiomyosarcoma is known to be rare from the previous reviews of a large number of malignant cervical tumors. The patient was a 66-year-old woman with irregular vaginal bleeding. She underwent modified radical hysterectomy and bilateral salpingooophorectomy. Histopathologically, we diagnosed the coexistence of uterine cervical leiomyosarcoma and cervical gastric-type adenocarcinoma in situ with endometrial lesions that had continuous and skip patterns and fallopian tubal lesions with a partial lesion. To the best of our knowledge, cases of synchronous leiomyosarcoma and cancers have not often been reported; only two cases of synchronous cervical leiomyosarcoma and cervical squamous cell carcinoma have been published. This case is the first presentation of coincidental primary cervical leiomyosarcoma and cervical gastric-type adenocarcinoma in situ. Additionally, we considered cervical gastric-type adenocarcinoma in situ with continuous lesions on the endometrium and skip lesions on the left fallopian tube.

Low-grade intraductal carcinoma of the salivary gland with prominent oncocytic change: a newly described variant.

AIMS: Low-grade intraductal carcinoma (LG-IDC) is a clinically indolent malignant tumour of the salivary glands. Because of its rarity, the histological variants of LG-IDC have not been well characterised. Herein, we describe five LG-IDC cases with prominent oncocytic change in the major salivary glands. METHODS AND RESULTS: We examined five cases, three males and two females (mean age = 63 years), of LG-IDC with oncocytic change. The sites affected by LG-IDC were the parotid and submandibular glands. The lesions were macroscopically unilocular or multilocular cysts with a solid tumour arising from the cyst wall. Smaller tumour cell nests were also observed. As with classic LG-IDC, the cyst wall was surrounded by myoepithelial cells with no invasive component. The tumour cells had abundant oncocytic cytoplasm and proliferated in a low-papillary, tubular or cribriform pattern. Immunohistochemically, the tumour cells were diffusely positive for pan-cytokeratin, S100, mammaglobin and antimitochondria antibody, and were negative for androgen receptor and gross cystic disease fluid protein-15. Unlike classic LG-IDC, some of these cases demonstrated focal invagination of myoepithelial cells in the intraductal tumour. CONCLUSION: Oncocytic LG-IDC should be recognised as a histologically unique variant of LG-IDC. Awareness of this entity is important to avoid erroneous diagnosis and inappropriate treatment for histological mimics.

Useful aspects of diagnosis of imprint cytology in intraoperative consultation of ovarian tumors: comparison between imprint cytology and frozen sections.

BACKGROUND: In the intraoperative consultation of ovarian tumors, the histological diagnosis of frozen sections (FS) of large tumors is frequently difficult because of the limited number of tumor samples. The application of imprint cytology (IC), in which samples are obtained from wide areas of the tumors, is useful for intraoperative consultation. However, the useful aspects of IC have not been clearly defined. The present study is a detailed comparison of IC and FS that clearly defines the useful aspects of IC. METHODS: Fifty-five cases of ovarian tumors that were examined using both IC and FS were evaluated. The histological diagnoses consisted of benign (16), borderline (6), and malignancy (33). All of the malignant tumors consisted of various types of carcinoma. RESULTS: Benignity and malignancy were accurately diagnosed by both IC and FS. In the borderline group, the diagnostic accuracy of IC was very low (1/6: 16.6%) compared with FS (4/6: 66.6%). The diagnostic accuracy including benign, borderline, and malignant groups was 90.9% (50/55) for IC and 96.3% (53/55) for FS. Concerning the diagnosis of the types of carcinoma, the overall diagnostic accuracy of IC (25/31: 80.6%) was greater than that of FS (21/31: 67.7%), especially for the diagnosis of clear cell carcinoma (IC, 100%; FS, 80%) and mixed carcinoma (IC, 66.6%; FS, 16.6%). CONCLUSION: The useful aspects of IC in the intraoperative consultation are the diagnosis of benignity or malignancy and the accuracy of diagnosing clear cell carcinoma and mixed carcinoma.

Cystic Endometrioma with Coexisting Fibroma Originating in a Supernumerary Ovary in the Rectovaginal Pouch.

A supernumerary ovary is an exceedingly rare disorder, in which the structure containing ovarian tissue is located at some distance from the normally placed ovary. 16 cases of endometriosis or tumors originating in a supernumerary ovary have been published in the English literature, but no case of coexisting endometriosis and a tumor has been published. We present the case of a 40-year-old female with cystic endometrioma with coexisting fibroma originating in a supernumerary ovary in the rectovaginal pouch. The present case is the first to be reported with coexisting endometriosis and a tumor originating in a supernumerary ovary. Our experience with this case and the results of our previous studies of rectovaginal endometriosis indicated that the possibility of originating in a supernumerary ovary shall be examined in cases of cystic endometrioma in the rectovaginal pouch.

Occult Breast Lobular Carcinoma with Numerous Circulating Tumor Cells in Peripheral Blood.

We experienced a very rare case of occult breast lobular carcinoma with numerous circulating tumor cells in peripheral blood. The diagnosis was very difficult because there were no symptoms of breast cancer and the preceding chief complaints such as general fatigue and weight loss or abnormality of peripheral blood findings were suggestive of a hematological disease. We could make a correct diagnosis of this case by checking the findings of complete blood count and bone marrow biopsy at the same time using immunohistochemistry.

Laparoscopic resection of an intra-abdominal esophageal duplication cyst: a case report and literature review.

Duplication of the alimentary tract is a rare congenital malformation that occurs most often in the abdominal region, whereas esophageal duplication cyst develops typically in the thoracic region but occasionally in the neck and abdominal regions. Esophageal duplication cyst is usually diagnosed in early childhood because of symptoms related to bleeding, infection, and displacement of tissue surrounding the lesion. We recently encountered a rare adult case of esophageal duplication cyst in the abdominal esophagus. A 50-year-old man underwent gastroscopy, endoscopic ultrasonography, computed tomography, and magnetic resonance imaging to investigate epigastric pain and dysphagia that started 3 months earlier. Imaging findings suggested esophageal duplication cyst, and the patient underwent laparoscopic resection followed by intraoperative esophagoscopy to reconstruct the esophagus safely and effectively. Histopathological examination of the resected specimen revealed two layers of smooth muscle in the cystic wall, confirming the diagnosis of esophageal duplication cyst.