Unusual presentation of breast adenoid cystic carcinoma resembling adenomyoepithelioma with multiple distinct foci.

We describe an unusual case of multifocal breast adenoid cystic carcinoma (AdCC) with adenomyoepitheliomatous morphology. Most breast AdCCs are unifocal and only four cases of multifocal AdCC have been reported previously, however, to our best knowledge, multifocality in AdCC confirmed by molecular analysis has not been reported, so this report adds to the literature on this unique presentation. An 80-year-old woman presented with a left breast mass at 1 o'clock and non-mass enhancement lesion at 5 o'clock on imaging. Incisional biopsy at 1 o'clock showed AdCC based on histopathological features and MYB rearrangement by fluorescent in situ hybridization (FISH). As AdCC involved the margins and the non-mass enhancing lesion remained, mastectomy was performed. Microscopically, the lesion at 5 o'clock demonstrated multinodularity and a biphasic epithelial-basaloid/myoepithelial pattern. Although histological features resembled adenomyoepithelioma, MYB rearrangement was identified on FISH, so the 5 o'clock lesion was also diagnosed as AdCC showing an adenomyoepitheliomatous pattern. This unusual presentation is a potential diagnostic pitfall, so pathologists should consider AdCC as a possible differential diagnosis of multifocal basaloid breast tumors with adenomyoepitheliomatous features.

A Comprehensive Study of the Immunophenotype and its Clinicopathologic Significance in Adult T-Cell Leukemia/Lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell tumor caused by human T-lymphotropic virus type 1 (HTLV-1). The typical ATLL immunophenotypes are described in the 2017 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (positive: CD2, CD3, CD5, CD4, and CD25; negative: CD7, CD8, and cytotoxic markers; and partially positive: CD30, CCR4, and FOXP3). However, limited studies are available on the expression of these markers, and their mutual relationship remains unknown. Furthermore, the expression status of novel markers associated with T-cell lymphomas, including Th1 markers (T-bet and CXCR3), Th2 markers (GATA3 and CCR4), T follicular helper markers (BCL6, PD1, and ICOS), and T-cell receptor (TCR) markers, and their clinicopathologic significance is unclear. In this study, we performed >20 immunohistochemical stains in 117 ATLL cases to determine the comprehensive immunophenotypic profile of ATLL, which were compared on the basis of clinicopathologic factors, including morphologic variants (pleomorphic vs anaplastic), biopsy locations, treatments, Shimoyama classification-based clinical subtype, and overall survival. CD3+/CD4+/CD25+/CCR4+ was considered a typical immunophenotype of ATLL, but approximately 20% of cases did not conform to this pattern. Simultaneously, the following new findings were obtained: (1) most cases were negative for TCR-ß and TCR-δ (104 cases, 88.9%), indicating the usefulness of negative conversion of TCR expression to provide differentiation from other T-cell tumors; (2) the positivity of CD30 and CD15 and the negativity of FOXP3 and CD3 were significantly associated with anaplastic morphology; and (3) atypical cases, such as T follicular helper marker-positive (12 cases, 10.3%) and cytotoxic molecule-positive cases (3 cases, 2.6%), were identified. No single markers could predict the overall survival among patients with acute/lymphoma subtypes of ATLL. The results of this study illustrate the diversity of ATLL phenotypes. In T-cell tumors occurring in HTLV-1 carriers, the possibility of ATLL should not be eliminated even when the tumor exhibits an atypical phenotype, and the confirmation of HTLV-1 in the tissue is recommended.

[A Trial of the Prevention of Postoperative Acute Exacerbation of Interstitial Pneumonia in Patients with Lung Cancer].

On preventing postoperative acute exacerbation (AE) of interstitial pneumonia (IP) in patients with lung cancer, the effect of administration of sivelestat sodium, steroids and erythromycin (EM) was assessed in 24 patients who was diagnosed as having IP and underwent surgery between April 2007 and October 2016. Oral administration of EM (400 mg) was started one week before the surgery, and methylprednisolone (125 mg) was administered intravenously at the time of anesthesia induction, postoperative day 1 and 2. Sivelestat sodium was administered intravenously at 4.8 mg/kg/day during the surgery, which was continued for 3-5 days. AEs occurred in two cases (8.3%). One patient developed AEs on postoperative day 5 and died in the hospital on postoperative day 76. The other patient developed AEs on postoperative day 38 and died in the hospital on postoperative day 43. In addition to the perioperative administration of steroids and EM in patients with lung cancer and IP, intraoperative administration of sivelestat sodium was suggested to be safe and to potentially prevent AEs.

Bilateral oncoplastic breast-conserving surgery with volume replacement technique using the omental flap: a case report.

BACKGROUND: Many oncoplastic volume replacement techniques have been reported, however, it is generally difficult to utilize a single distant flap for bilateral breast carcinomas. CASE PRESENTATION: We report a case of bilateral multiple breast carcinomas successfully treated with immediate volume replacement technique with an omental flap. Bilateral partial mastectomies were performed for bilateral breast carcinomas (one in the left breast and two in the right breast). The pedicled omental flap was laparoscopically harvested, and divided at the mid-portion of the flap. The proximal half of the flap was used to fill the right defect, and the distal half of the flap filled two defects in the left breast. Cosmetic outcome was excellent with minimal donor-site scars. CONCLUSIONS: The omental flap can be considered for highly selected patients with bilateral breast carcinomas.

Predictive value of ductal carcinoma in situ with invasive breast cancer in core needle biopsies for final pathologic size of intraductal elements.

Preoperative evaluations of the size of ductal carcinoma in situ (DCIS) extension in invasive breast cancer (IBC) are problematic and markers of the actual size of DCIS remain elusive. This study aimed to quantify DCIS on core needle biopsy (CNB) and investigated its association with degree of DCIS extension on paired resection specimens, instead of with presence or absence of an extensive intraductal component or margin status as in earlier studies. This series examined 150 IBCs diagnosed from paired CNB and resection specimens. The DCIS/invasion ratio was calculated using the sum of each element size from CNB. In resection specimens, cases in which the greatest dimension of DCIS extension was longer than the greatest dimension of invasive size were defined as extended DCIS (Ext-DCIS). DCIS/invasion ratio level correlated positively with the degree of Ext-DCIS (P = 0.003). Using receiver operating characteristic curve analysis, setting cases with the subgroup of DCIS extension with greatest dimension > 2.5 times that of the invasive size in the resection specimen (Ext-DCIS > 2.5) as the positive class provided the best discrimination ability for DCIS/invasion ratio (0.375). In multivariate analysis, DCIS/invasion ratio > 0.375 was significantly associated with Ext-DCIS > 2.5 (P = 0.033). In conclusion, DCIS/invasion ratio > 0.375 in CNB was identified as a predictor of Ext-DCIS > 2.5 in resection specimens, suggesting that an approach combining DCIS/invasion ratio from CNB with preoperative staging may better predict the extent of DCIS and facilitate better surgical planning.

Lymphoepithelial carcinoma of the parotid gland: a unique example showing p16 immunoreactivity.

Lymphoepithelial carcinoma (LEC) shows characteristic histology of nesting growth of tumor cells with unclear differentiation against the lymphoid stroma background. Although rare in salivary glands, it has previously been recognized as a type of undifferentiated carcinoma but is currently clearly defined as an independent disease separate from undifferentiated carcinoma. We report a case of LEC that developed in the parotid gland and was immunohistochemically positive for p16, which suggested the causative involvement of human papillomavirus (HPV). The patient was a 38-year-old Japanese male aware of mass formation in the left parotid area for 8 years. Parotidectomy was performed and there have been no signs of recurrence or metastasis for 18 month post-operation. The tumor was histologically typical except for Epstein-Barr virus (EBV)-encoded small RNA (EBER)-negative in situ hybridization (ISH), but p16-positivity by immunohistochemistry, and also frequent contact with extended and expanded pre-existing ductal structures. Although usually strongly associated with EBV infection, the tumor could be regarded to have eventually reached completion as a LEC lesion associated with HPV infection possibly through the pathway shared with squamous cell carcinoma. EBER-ISH remains the most promising index for confirming diagnosis of LEC, but EBV-negative result alone should not prevent diagnosis of LEC.

A refractory pleural effusion caused by a pleural capillary hemangioma.

A 69-year-old man presented with a left pleural effusion. Even after repeated drainage, the pleural effusion had been increasing for more than two years. Thoracoscopy unexpectedly showed a pleural mass on the parietal pleura, and it was completely removed. The diagnosis was pleural capillary hemangioma, and the effusion has not recurred after the resection. Pleural hemangioma is one of the crucial differential diagnoses of refractory pleural effusion.

A long-term survivor keeping in a complete response without treatment after pemetrexed maintenance therapy for advanced non-squamous non-small cell lung cancer.

Pemetrexed has significant efficacy for some non-squamous non-small cell lung cancer cases, as demonstrated in the current case. For those patients, pemetrexed administration should be carefully considered.

Spiradenoma of the breast: a rare diagnostic pitfall in the evaluation of solid-basaloid breast lesions with a dual cell population.

Breast spiradenoma is extremely rare, with only 4 cases reported previously. We describe an instructive case of breast spiradenoma resembling adenoid cystic carcinoma (AdCC). A 71-year-old woman underwent excisional biopsy of a breast mass after a conclusive diagnosis was unable to be obtained from core needle biopsy showing an AdCC-like pattern. Histopathologically, the lesion demonstrated solid and cribriform foci comprising basaloid cells, luminal cells, and eosinophilic hyaline material, reminiscent of solid-basaloid AdCC, alongside convoluted lumens, stromal edema, lymphocytic infiltration, and c-kit negativity. On molecular analysis, neither MYB fusion genes nor CYLD gene abnormalities were identified. These results were supportive of spiradenoma. Salivary gland- and skin adnexal-type tumors are challenging to diagnose due to morphological overlaps. This case, highlighting histopathological and molecular features, shows that breast spiradenoma can be a diagnostic pitfall among the differential diagnoses of AdCC.

miR-935 Inhibits Oral Squamous Cell Carcinoma and Targets Inositol Polyphosphate-4-phosphatase Type IA (INPP4A).

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a common malignancy with poor prognosis. Therefore, novel therapeutic options are needed to improve prognosis of OSCC. Recently, microRNAs (miRs) have received increasing attention as a potential therapeutic tool for carcinomas. However, no definitive miR-based drugs for patients with OSCC have been reported to date. The aim of this study was to identify new miRs potentially involved in cellular processes associated with OSCC malignancy, which could lead to novel therapeutic strategies. MATERIALS AND METHODS: We identified miRs that are modulated in OSCC and possibly regulate OSCC malignancy, using miR microarray on OSCC cell lines. RESULTS: miR-935 and miR-509-3p were down-regulated in OSCC cell lines and patient tissues. When miR-935 was overexpressed in HSC-3-M3 cells, proliferation, migration, and invasion of the cell line was suppressed, whereas apoptosis was increased. Moreover, we showed that the gene inositol polyphosphate-4-phosphatase type I A (INPP4A) is a potential target whose expression is positively regulated by miR-935. CONCLUSION: miR-935 may function as a tumor suppressor by inhibiting OSCC malignancy via INPP4A induction. Therefore, miR-935 can be a new therapeutic candidate for OSCC treatment.

Quantitative digital image analysis of tumor-infiltrating lymphocytes in HER2-positive breast cancer.

As visual quantification of the density of tumor-infiltrating lymphocytes (TILs) lacks in precision, digital image analysis (DIA) approach has been applied in order to improve. In several studies, TIL density has been examined on hematoxylin and eosin (HE)-stained sections using DIA. The aim of the present study was to quantify TIL density on HE sections of core needle biopsies using DIA and investigate its association with clinicopathological parameters and pathological response to neoadjuvant chemotherapy in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The study cohort comprised of patients with HER2-positive breast cancer, all treated with neoadjuvant anti-HER2 therapy. DIA software applying machine learning-based classification of epithelial and stromal elements was used to count TILs. TIL density was determined as the number of TILs per square millimeter of stromal tissue. Median TIL density was 1287/mm2 (range, 123-8101/mm2). A high TIL density was associated with higher histological grade (P = 0.02), estrogen receptor negativity (P = 0.036), and pathological complete response (pCR) (P < 0.0001). In analyses using receiver operating characteristic curves, a threshold TIL density of 2420/mm2 best discriminated pCR from non-pCR. In multivariate analysis, high TIL density (> 2420/mm2) was significantly associated with pCR (P < 0.0001). Our results indicate that DIA can assess TIL density quantitatively, machine learning-based classification algorithm allowing determination of TIL density as the number of TILs per unit area, and TIL density established by this method appears to be an independent predictor of pCR in HER2-positive breast cancer.

Radiation-induced sarcoma in a 10-year survivor with stage IV EGFR-mutated lung adenocarcinoma.

A 70-year-old Japanese man with stage IV EGFR-mutated lung adenocarcinoma complained of right mild back pain. The patient had been heavily treated with several cytotoxic or molecular targeted agents for 10 years and received a palliative radiation therapy of 2nd sacral vertebra 5 years ago. Computed tomography showed the abnormal lesion in right iliopsoas muscle. A pathological examination confirmed undifferentiated pleomorphic sarcoma, consistent with the diagnosis of radiation-induced sarcoma (RIS). Since RIS is a rare late-onset complication of radiation therapy, to our knowledge, this is the first report of RIS that was associated with advanced lung cancer and detected after palliative radiation therapy. The careful long-term follow-up is thus necessary even after palliative radiation therapy and we have to be aware of the existence of RIS.

Resection of liposarcoma of the greater omentum: A case report and literature review.

INTRODUCTION: Liposarcoma usually occurs in the retroperitoneum and limbs. Liposarcoma of the greater omentum is rare, and most information of such liposarcomas has come from case reports. PRESENTATION OF CASE: A 60-year-old woman was found to have an 8-cm intra-abdominal mass (suspected lipoma) by computed tomography. At the age of 63 years, she underwent a medical examination and a mass was palpated in the abdomen. Contrast-enhanced computed tomography and magnetic resonance imaging confirmed the presence of a huge intra-abdominal tumor with the omental artery passing through the mass. The tumor was simply resected. Histopathologically, the tumor was diagnosed as a well-differentiated liposarcoma, and the resection margin was microscopically negative. The patient had developed no recurrence or complications 9 months postoperatively. DISCUSSION: Liposarcoma of the greater omentum is rare, and differentiation of liposarcoma from other tumors is challenging. Adjuvant therapy has not been established as an effective treatment, and radical (R0) resection of the tumor is recommended. Our case of liposarcoma of the greater omentum was surgically managed with good outcomes. CONCLUSION: The diagnosis of liposarcoma with a lipomatous tumor is challenging, and resection should be considered for huge intra-abdominal lipomatous tumors.

Thirteen cases of pulmonary dirofilariasis in a single institution in Okinawa Island.

Pulmonary dirofilariasis is an infection caused by Dirofilaria immitis, which is an endemic parasite in Japan. We experienced 13 surgical cases of pulmonary dirofilariasis in our hospital. Of the 13 patients, 61.5% were men. The responsible lesions were located in the right lung in all cases, and 76.9% of them were in the lower lobe. Histologically, 12 cases showed necrotic nodules with peripheral granuloma with worms inside the pulmonary artery. One case did not show a necrotic nodule but showed only thickening and hyalinization of the pulmonary artery wall with a degenerated worm inside. Eosinophils were found histologically in all cases. Thirteen cases of dirofilariasis in one institution seem to be the largest number in Japan, based on previous reports. One reason for this increased prevalence may be the hot and humid climate of our prefecture considering the ecology of the mosquito as a vector. Elastic staining and eosinophils in peripheral granulomatous areas can contribute to the diagnosis when the worms are degenerated.

Triple primary cancer of the head and neck, skin and prostate: A case report and literature review.

Second primary cancer (SPC) is an important prognostic factor for patients with head and neck cancer (HNC); therefore, the association between the prognosis and development of SPC has been well-reported. The use of 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is valuable to examine cancer stage, evaluate treatment responses and investigate suspected relapses or metastases. In the present study, the case of a male patient who was diagnosed with three primary cancer types, including well to moderately differentiated squamous cell carcinoma (SCC) of the mandible, axillary cutaneous poorly differentiated SCC and prostate adenocarcinoma, was described. Among these, mandible cancer was the first diagnosed when the patient was 70 years of age. Synchronous skin and prostate cancer (PRC) types then developed 3 years later. To the best of our knowledge, this is the first report of the aforementioned combination of cancer types. Postoperative FDG-PET was not performed as no lesions of recurrence or metastases of mandible cancer were found. Three years later, the PRC was asymptomatic and was incidentally detected by FDG-PET performed for a preoperative evaluation of skin cancer. It was indicated that FDG-PET could be utilized in patients with HNC due to there being no accurate FDG-PET protocol to detect SPC over a long-term follow-up.

Dedifferentiated liposarcoma of the oral floor: A case study and literature review of 50 cases of head and neck neoplasm.

Dedifferentiated liposarcoma (DDLS) has a relatively poor prognosis, however this neoplasm rarely occurs in the head and neck. To date, no definite protocol has been established for the diagnosis and treatment of head and neck DDLS. The present study reports the case of a 69-year-old male patient with DDLS of the oral floor. To the best of our knowledge, this is the first documented case of oral floor DDLS. In addition, this is the first reported case with the development of a second primary malignancy following the treatment of head and neck DDLS. A literature review of 50 cases of head and neck DDLS revealed that preoperative biopsy is not reliable for the diagnosis of these tumors and an accurate pathological diagnosis with total resection is preferred.

Lymphatic vessel involvement is predictive for lymph node metastasis and an important prognostic factor in endometrial cancer.

BACKGROUND: Lymphovascular space involvement is reported to be an important risk factor in endometrial cancer. This study was conducted to evaluate the separate prognostic effects of lymphatic invasion and venous invasion on the outcomes of patients with endometrial cancer. METHODS: From 2006 to 2013, 189 histologically confirmed endometrial cancer patients were examined. To study the venous invasion (v) of the endometrial cancer, Victoria blue-H&E staining-which positively stains the elastic fibers of vessels-was performed. Immunohistochemical staining with D2-40 was used to study the lymphatic invasion (ly) of the endometrial cancer. RESULTS: The median age of the patients was 57 (range 25-84) years. ly(+) and/or v(+) patients were significantly more likely to present an advanced cancer stage, G3 tumor, and deep myometrial invasion than ly(-)/v(-) patients. The incidence of lymph node metastasis was high in ly(+) patients, and that of ovarian metastasis was high in v(+) patients. Lymphatic vessel invasion was significantly correlated with regional lymph node metastasis. We found a significantly higher incidence of distant metastasis in ly(+) patients. Most recurrences in ly(+)/v(-) patients occurred in lymph nodes, while those in ly(+)/v(+) patients occurred mainly at distant organs. Finally, the prognosis was significantly poorer for ly(+) patients, in whom lymphatic invasion was an independent prognostic factor along with distant metastasis. CONCLUSIONS: Our study suggests that by separately evaluating lymphatic invasion and blood vessel invasion in endometrial cancer cases, useful information for predicting lymph node metastasis and recurrence sites as well as prognostic information can be obtained.

Nuclear features of infiltrating urothelial carcinoma are distinguished from low-grade noninvasive papillary urothelial carcinoma by image analysis.

Recent advances in computer technology have been made and image analysis (IA) has been introduced into pathological fields. The present study aimed to investigate the utility of IA for the evaluation of nuclear features and staining of immunohistochemistry (IHC) for Ki-67, p53 and GATA-binding protein 3 (GATA-3) in urothelial carcinoma tissue samples. A total of 49 cases of urothelial carcinoma tissue samples were obtained by transurethral resection of bladder tumors, which included 11 low-grade papillary urothelial carcinomas (LGPUCs), 1 non-invasive high-grade urothelial carcinoma and 37 infiltrating urothelial carcinomas (IUCs). Whole slide imaging (WSI) and IA were performed in Feulgen reaction and IHC-stained tissue samples. There was a significant difference in the average nuclear density, standard deviation (SD) of nuclear size and SD of nuclear minimum and maximum diameter between LGPUC and IUC, which is equivalent to the diagnostic features of IUC in nuclear variability, and hyperchromatic nuclei. In addition, the present study revealed that the SD of nuclear density was significantly different between the two groups. Regarding IA in IHC-stained tissue samples, Ki-67 was significantly overexpressed in IUC. Furthermore, the GATA-3 expression level in IUC samples with muscle invasion was significantly downregulated compared with that in non-muscle invasive tumors. The results of the present study suggest that IA in combination with WSI may be a beneficial tool for evaluating morphometric characteristics and performing semi-quantitative analysis of IHC.

Non-traumatic rupture of the superior thyroid artery with concomitant parathyroid adenoma and multinodular goiter.

Cervical hemorrhage due to non-traumatic, spontaneous rupture of the thyroid artery is rare, which usually results from arterial abnormalities or parathyroid or thyroid disorders. This report describes a 72-year-old woman who presented with a sore throat and slight neck swelling. Computed tomography (CT) revealed a large hematoma in the neck and mediastinum, due to extravasation from the major branch of the left superior thyroid artery. A follow-up CT the next day demonstrated that the extravasation had resolved. Subsequent surgery revealed both parathyroid adenoma and multinodular goiter in the resected thyroid gland. A transient elevation of parathyroid hormone occurred immediately after the hemorrhage, suggesting that the hemorrhage may have been related to the parathyroid adenoma. However, ruptured thyroid arteries were not observed on histopathological examination of the resected tissue.