Diagnostic utility of cytology in a patient with Epstein-Barr virus-positive mucocutaneous ulcer in palatine tonsils: A case report.

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly established immunodeficiency-related disease. Herein, we report a case of EBVMCU and focus on its cytological usefulness for diagnosis. An 82-year-old man manifested pharyngalgia, dysphagia, and oral pain. His medical history included rheumatoid arthritis that had been treated with methotrexate. Clinically, peritonsillar abscess was suspected, but since neoplastic lesions, including malignant lymphoma (ML), could not be excluded, a series of cytohistological examination was attempted. Despite some alarming findings (e.g., frequent mitoses), fine-needle aspiration and touch imprint cytology consistently revealed a heterogeneous population of lymphoid and plasmacytoid cells with mild nuclear atypia. The final diagnosis of EBVMCU was established based on the permanent histologic specimen; however, retrospectively, cytology was more representative of the benign nature of the lesion than histology, helping a great deal to differentiate it from ML. Cytology can be a useful tool for the correct diagnosis of EBVMCU.

Carcinoma showing thymus-like elements (CASTLE) with amyloid deposition in the parotid gland.

Carcinoma showing thymus-like elements (CASTLE) is a rare tumor that commonly occurs in the thyroid gland. Extrathyroidal CASTLE is rarer, and only 11 cases of CASTLE of major salivary glands have been reported to date. We report the first case of amyloid deposition in parotid CASTLE. A 63-year-old man presented with a slowly growing mass in the left parotid region. Computed tomography revealed an approximately 28 × 23 mm mass lesion in the left parotid gland, and squamous cell carcinoma was suspected on biopsy. The patient underwent a parotidectomy with neck dissection. Morphologically, the tumor cells were squamoid and formed nests with lymphoid infiltration. Immunohistochemically, the tumor cells exhibited immunoreactivity for CD5, CD117/c-kit and Bcl-2, p40, and CK5 but not for p16. We diagnosed the tumor as parotid CASTLE. Amyloid deposition was also observed in the primary tumor and metastatic lymph node lesions, which were immunoreactive for cytokeratin 5. Tumor cytokeratin-derived amyloid deposition may be one of characteristics of parotid CASTLE.

Recurrent urethral tumor with neuroendocrine differentiation in a female patient after radical cystectomy for bladder cancer.

Introduction: Urethral recurrence after radical cystectomy in female patients with bladder cancer is relatively uncommon. Recurrent bladder tumors with neuroendocrine differentiation are extremely rare. Case presentation: A 71-year-old female patient who underwent radical cystectomy for bladder cancer presented with vaginal bleeding 19 months postoperatively. She was diagnosed with bladder cancer urethral recurrence. Urethral tumor en-bloc resection with the anterior vaginal wall was performed by combining abdominal and vaginal approaches. Pathological examination revealed a recurrent tumor of urothelial bladder cancer containing small-cell carcinoma components. Conclusion: This case is the first report of a recurrent tumor with small-cell carcinoma in the female urethra after radical cystectomy for pure urothelial carcinoma.

Prediction Formula for Pathological Depth of Invasion From Clinical Depth of Invasion in Tongue Squamous Cell Carcinoma (SCC) Stage I/II Cases.

BACKGROUND:  The depth of invasion (DOI) of tongue squamous cell carcinoma (SCC) is an important prognostic factor. The definition is clear for pathological DOI (pDOI), but the treatment strategy is determined by the preoperative clinical DOI (cDOI). Few studies have investigated the difference between these DOIs. The purpose of this study was to obtain the correlation equation between cDOI and pDOI for Stage I/II tongue SCC and to consider the points to be noted in actual clinical practice. METHODS:  In this retrospective study, 58 patients with clinical stage I/II tongue SCC were included. Correlations between cDOI and pDOI were obtained for all 58 cases, as well as for 39 cases which excluded superficial and exophytic lesions. RESULTS:  The overall cDOI and pDOI median values were 8.0 and 5.5 mm, respectively; the 2.5 mm reduction was significant (p < 0.01). The correlation equation was pDOI = 0.81 × cDOI-0.23 (r = 0.73). Furthermore, re-analysis of the 39 cases revealed that pDOI = 0.84 × cDOI-0.37 (r = 0.62). Hence, a derived equation pDOI = 0.84 × (cDOI-0.44) was obtained to predict pDOI from cDOI. CONCLUSIONS:  This study indicated that it is necessary to consider contraction due to specimen fixation by subtracting the thickness of the mucosal epithelium. Clinical T1 cases with a cDOI of 5 mm or less had a pDOI of 4 mm or less, and it would be expected to have low positive rate of neck lymph node metastasis.

Effects of dimension reduction of hyperspectral images in skin gross pathology.

BACKGROUND: Hyperspectral imaging (HSI) is an emerging modality for the gross pathology of the skin. Spectral signatures of HSI could discriminate malignant from benign tissue. Because of inherent redundancies in HSI and in order to facilitate the use of deep-learning models, dimension reduction is a common preprocessing step. The effects of dimension reduction choice, training scope, and number of retained dimensions have not been evaluated on skin HSI for segmentation tasks. MATERIALS AND METHODS: An in-house dataset of HSI signatures from pigmented skin lesions was prepared and labeled with histology. Eleven different dimension reduction methods were used as preprocessing for tumor margin detection with support vector machines. Cluster-wise principal component analysis (ClusterPCA), a new variant of PCA, was proposed. The scope of application for dimension reduction was also investigated. RESULTS: The components produced by ClusterPCA show good agreement with the expected optical properties of skin chromophores. Random forest importance performed best during classification. However, all methods suffered from low sensitivity and generalization. CONCLUSION: Investigation of more complex reduction and segmentation schemes with emphasis on the nature of HSI and optical properties of the skin is necessary. Insights on dimension reduction for skin tissue could facilitate the development of HSI-based systems for cancer margin detection at gross level.

Hyperspectral imaging for tumor segmentation on pigmented skin lesions.

Significance: Malignant skin tumors, which include melanoma and nonmelanoma skin cancers, are the most prevalent type of malignant tumor. Gross pathology of pigmented skin lesions (PSL) remains manual, time-consuming, and heavily dependent on the expertise of the medical personnel. Hyperspectral imaging (HSI) can assist in the detection of tumors and evaluate the status of tumor margins by their spectral signatures. Aim: Tumor segmentation of medical HSI data is a research field. The goal of this study is to propose a framework for HSI-based tumor segmentation of PSL. Approach: An HSI dataset of 28 PSL was prepared. Two frameworks for data preprocessing and tumor segmentation were proposed. Models based on machine learning and deep learning were used at the core of each framework. Results: Cross-validation performance showed that pixel-wise processing achieves higher segmentation performance, in terms of the Jaccard coefficient. Simultaneous use of spatio-spectral features produced more comprehensive tumor masks. A three-dimensional Xception-based network achieved performance similar to state-of-the-art networks while allowing for more detailed detection of the tumor border. Conclusions: Good performance was achieved for melanocytic lesions, but margins were difficult to detect in some cases of basal cell carcinoma. The frameworks proposed in this study could be further improved for robustness against different pathologies and detailed delineation of tissue margins to facilitate computer-assisted diagnosis during gross pathology.

The implicated clinical factors for outcomes in 304 patients with salivary duct carcinoma: Multi-institutional retrospective analysis in Japan.

BACKGROUND: Salivary duct carcinoma (SDC) is a high-grade salivary malignancy that frequently occurs as the carcinomatous component of carcinoma ex pleomorphic adenoma. We herein examined the clinical factors affecting outcomes in a large cohort of SDC. METHODS: We selected 304 SDC cases and investigated clinical characteristics and the factors affecting outcomes. RESULTS: The median age of the cases examined was 68 years, the most common primary site was the parotid gland (238 cases), and there was a male predominance (M/F = 5:1). Outcomes were significantly worse when the primary tumor site was the minor salivary glands (SG) than when it was the major SG. Outcomes were also significantly worse in pN(+) cases (161 cases) than in pN0 cases, particularly those with a metastatic lymph node number ≥11. The cumulative incidence of relapse and distant metastases was significantly higher in stage IV cases than in stage 0-III cases. CONCLUSIONS: The absolute number of lymph node metastases, higher stages, and the minor SG as the primary tumor site were identified as factors affecting the outcome of SDC.

Adrenocortical Carcinoma Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration.

Adrenocortical carcinoma (ACC) is a rare malignancy with a very poor prognosis. A 77-year-old man underwent imaging studies due to poorly controlled hypertension, which revealed a mass measuring 43 mm in diameter near the left adrenal gland. There were no findings indicative of pheochromocytoma. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed for the preoperative pathological evaluation, and the findings indicated a possibility of ACC. Based on these results, curative surgery was performed. If the diagnosis of pheochromocytoma is excluded, then EUS-FNA for adrenal lesions is relatively safe. It can also be used for the preoperative diagnosis of ACC.

A case of cerebral infarction due to pleomorphic carcinoma of the lung.

BACKGROUND: With the increase in endovascular treatment, reports of embolism other than thrombus are scattered, but intracranial tumorigenic embolism is rare and difficult to diagnose. Here, we describe a case of a tumorigenic embolism in a patient with lung cancer whose invasion into the vascular system was not detected on preoperative whole-body imaging. CASE DESCRIPTION: A 66-year-old man who was hospitalized to undergo radiotherapy for pulmonary carcinoma suddenly developed left hemiplegia. He exhibited atrial fibrillation, and emergent radiographic examination revealed a right middle cerebral artery occlusion. Urgent mechanical embolectomy was performed, with successful revascularization. The excised embolus had a unique morphology and was pathologically diagnosed as a cerebral embolism caused by pleomorphic pulmonary carcinoma. CONCLUSION: Tumor-derived cerebral embolism is extremely rare, but it is necessary to consider it as a potential source of embolism during differential diagnosis in patients with malignant tumors.

Podoplanin is an efficient predictor of neck lymph node metastasis in tongue squamous cell carcinoma with low tumor budding grade.

The current study investigated the efficacy of podoplanin expression in tumor budding cells as a predictor of neck lymph node metastasis (NLM) in patients with tongue squamous cell carcinoma (SCC) of low tumor budding grade (TBG). A total of 99 patients with early T-stage tongue SCC of any clinical N status who received the initial curative treatment were enrolled. The association between podoplanin expression and NLM was immunohistochemically analyzed, with a focus on tongue SCC with low TBG. The disease-specific survival (DSS) rate was 77% at 5 years, and a significant difference was observed between the NLM-positive and NLM-negative groups, and between the low (n=77) and high (n=22) TBG groups. In the low TBG group, there was a significant difference in DSS between the NLM-positive and NLM-negative groups. The multivariate analysis showed that lymphatic vessel invasion (ly) [odds ratio (OR)=11.5, 95% confidence interval (CI): 1.50-87.6; P=0.02] and podoplanin expression (OR=7.07, 95% CI: 1.80-27.7; P=0.005) were significantly correlated with NLM. Furthermore, negative predictive values (NPV) of ly and podoplanin expression for NLM were 75% and 88%, respectively. Considering the balance of stratification case number adding to ratio, NLM-negative prediction by podoplanin was more significant than that by ly for the low TBG group. The results of the present study demonstrated that podoplanin expression in tumor budding is an independent and efficient predictor of NLM in the tongue SCC with low TBG. The low TBG and podoplanin-negative cases may be candidates for the wait and watch policy, therefore, reducing inappropriate elective neck lymph node dissections.

Tumor-to-tumor metastasis from appendiceal adenocarcinoma to an ovarian mature teratoma, mimicking malignant transformation of a teratoma: a case report.

BACKGROUND: Tumor-to-tumor metastasis (TTM) is a rare but well-documented phenomenon that is defined as metastasis in a histologically distinct tumor. Ovarian mature teratomas (OMTs) can coexist with various cancers by malignant transformation, which may make it difficult to distinguish these from TTM. Herein, we report a case of TTM from appendiceal adenocarcinoma to the OMT, mimicking the malignant transformation of OMT. CASE PRESENTATION: A 67-year-old Japanese woman underwent abdominal total hysterectomy and bilateral salpingo-oophorectomy for an ovarian tumor in another hospital. She was initially diagnosed with mucinous carcinoma/carcinoid arising in the OMT. One year after surgery, she was referred to our hospital after the presentation of increased appendiceal mass. Cecal biopsy targeting an appendiceal tumor revealed scattered mucinous cells with signet ring features, which were morphologically similar to the malignant components in the previously diagnosed right OMT. Both the appendiceal adenocarcinoma and malignant components of the OMT stained positive for CK7, CK20, CDX-2, and SATB2 but negative for estrogen receptor, progesterone receptor, and pax-8. Finally, we confirmed the diagnosis of appendiceal goblet cell carcinoid metastasizing to the right OMT. The patient had tumor-bearing survival due to systemic chemotherapy administered for 35 months after the initial surgery. CONCLUSIONS: Awareness of the TTM phenomenon is important to avoid an incorrect diagnosis and to select the appropriate therapy when unusual malignancy is encountered in the OMTs.

Coexistence of endometrial mesonephric-like adenocarcinoma and endometrioid carcinoma suggests a Müllerian duct lineage: a case report.

BACKGROUND: Endometrial mesonephric-like adenocarcinomas exhibit classical histologic features of mesonephric carcinoma; however, it remains unclear whether these tumors represent mesonephric (Wolffian) carcinoma or endometrioid (Müllerian) carcinomas that closely mimic mesonephric carcinoma. CASE PRESENTATION: A 32-year-old Japanese primigravida presented with atypical vaginal bleeding. An endometrial biopsy suggested low-grade endometrioid carcinoma, and she was administered medroxyprogesterone acetate. Her tumor recurred 6 years later, and she underwent hysterectomy, salpingo-oophorectomy, and omentectomy, at which point she was diagnosed with mesonephric-like adenocarcinoma of the uterine endometrium. Retrospective pathological review of the initial biopsy confirmed coexisting low-grade endometrioid carcinoma and mesonephric-like adenocarcinoma of the uterine endometrium. On immunohistochemistry, the endometrioid carcinoma component was diffuse positive for estrogen and progesterone receptors but negative for thyroid transcription factor 1. However, the mesonephric-like adenocarcinoma component exhibited a mixture of estrogen receptor- and thyroid transcription factor 1-positive cells within the same glands. CONCLUSIONS: We encountered a patient with coexisting endometrial mesonephric-like adenocarcinoma and low-grade endometrioid carcinoma, which was treated using medroxyprogesterone acetate therapy, resulting in recurrence of mesonephric-like adenocarcinoma alone. These clinicopathological findings support the prevailing notions that mesonephric-like adenocarcinoma is a Müllerian adenocarcinoma exhibiting mesonephric differentiation.

Effects of the Geometrical Structure of a Honeycomb TCP on Relationship between Bone / Cartilage Formation and Angiogenesis.

A number of biomaterials have been developed, some of which already enjoy widespread clinic use. We have devised a new honeycomb tricalcium phosphate (TCP) containing through-and-through holes of various diameters to control cartilage and bone formation. However, the way in which the geometric structure of the honeycomb TCP controls cartilage and bone tissue formation separately remains unknown. In addition, an association has been reported between bone formation and angiogenesis. Therefore, in the present study, we investigated the relationship between angiogenesis and various hole diameters in our honeycomb TCP over time in a rat ectopic hard tissue formation model. Honeycomb TCPs with hole diameters of 75, 300, and 500 µm were implanted into rat femoral muscle. Next, ectopic hard tissue formation in the holes of the honeycomb TCP was assessed histologically at postoperative weeks 1, 2, and 3, and CD34 immunostaining was performed to evaluate angiogenesis. The results showed that cartilage formation accompanied by thin and poor blood vessel formation, bone marrow-like tissue with a branching network of vessels, and vigorous bone formation with thick linear blood vessels occurred in the TCPs with 75-µm, 300-µm, and 500-µm hole diameters, respectively. These results indicated that the geometrical structure of the honeycomb TCP affected cartilage and bone tissue formation separately owing to the induced angiogenesis and altered oxygen partial pressure within the holes.

Characterization and potential roles of bone marrow-derived stromal cells in cancer development and metastasis.

Background: The tumor microenvironment and its stromal cells play an important role in cancer development and metastasis. Bone marrow-derived cells (BMDCs), a rich source of hematopoietic and mesenchymal stem cells, putatively contribute to this tumoral stroma. However their characteristics and roles within the tumor microenvironment are unclear. In the present study, BMDCs in the tumor microenvironment were traced using the green fluorescent protein (GFP) bone marrow transplantation model. Methods: C57BL/6 mice were irradiated and rescued by bone marrow transplantation from GFP-transgenic mice. Lewis lung cancer cells were inoculated into the mice to generate subcutaneous allograft tumors or lung metastases. Confocal microscopy, immunohistochemistry for GFP, α-SMA, CD11b, CD31, CD34 and CD105, and double-fluorescent immunohistochemistry for GFP-CD11b, GFP-CD105 and GFP-CD31 were performed. Results: Round and dendritic-shaped GFP-positive mononuclear cells constituted a significant stromal subpopulation in primary tumor peripheral area (PA) and metastatic tumor area (MA) microenvironment, thus implicating an invasive and metastatic role for these cells. CD11b co-expression in GFP-positive cells suggests that round/dendritic cell subpopulations are possibly BM-derived macrophages. Identification of GFP-positive mononuclear infiltrates co-expressing CD31 suggests that these cells might be BM-derived angioblasts, whereas their non-reactivity for CD34, CD105 and α-SMA implies an altered vascular phenotype distinct from endothelial cells. Significant upregulation of GFP-positive, CD31-positive and GFP/CD31 double-positive cell densities positively correlated with PA and MA (P<0.05). Conclusion: Taken together, in vivo evidence of traceable GFP-positive BMDCs in primary and metastatic tumor microenvironment suggests that recruited BMDCs might partake in cancer invasion and metastasis, possess multilineage potency and promote angiogenesis.

The Role of Bone Marrow-Derived Cells during Ectopic Bone Formation of Mouse Femoral Muscle in GFP Mouse Bone Marrow Transplantation Model.

Multipotential ability of bone marrow-derived cells has been clarified, and their involvement in repair and maintenance of various tissues has been reported. However, the role of bone marrow-derived cells in osteogenesis remains unknown. In the present study, bone marrow-derived cells during ectopic bone formation of mouse femoral muscle were traced using a GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) mice were transplanted into C57BL/6 J wild type mice. After transplantation, insoluble bone matrix (IBM) was implanted into mouse muscle. Ectopic bone formation was histologically assessed at postoperative days 7, 14, and 28. Immunohistochemistry for GFP single staining and GFP-osteocalcin double staining was then performed. Bone marrow transplantation successfully replaced hematopoietic cells with GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts and osteocytes involved in ectopic bone formation were GFP-negative, whereas osteoclasts and hematopoietic cells involved in bone formation were GFP-positive. These results indicate that bone marrow-derived cells might not differentiate into osteoblasts. Thus, the main role of bone marrow-derived cells in ectopic osteogenesis may not be to induce bone regeneration by differentiation into osteoblasts, but rather to contribute to microenvironment formation for bone formation by differentiating tissue stem cells into osteoblasts.

Free-space-wave drop demultiplexing waveguide device fabricated by use of the interference exposure method.

Integration of free-space-wave add-drop multiplexers that consist of focusing grating couplers (FGCs) and distributed Bragg reflectors (DBRs) in thin-film waveguides have been investigated for construction of an intraboard wavelength-division-multiplexing optical interconnection. Compact optics of a Lloyd mirror configuration and a contact-type mask aligner were combined as an interference exposure system for fabrication of DBRs of 300 microm coupling length. DBRs were integrated with FGCs on a thin-film waveguide on a glass substrate for two-channel wavelength-drop demultiplexing from guided waves to free-space waves. Measured outcoupled wavelengths of two free-space waves from two pairs of a FGC and a DBR agreed with the design values of 845 and 849 nm.