Expression of p63 immunostaining in liquid-based cytology (BD SurePath) of breast fine-needle aspiration.

BACKGROUND: We performed p63 immunostaining to detect myoepithelial cells on BD SurePath liquid-based cytology (LBC) slides and examined whether this improved the diagnostic accuracy in breast fine-needle aspiration cytology (FNAC). METHODS: We examined the diagnostic accuracy using the LBC-p63 immunostaining slides of 298 lesions obtained from July 2010 to August 2016. RESULTS: We defined the cutoff values for malignancy as follows: (1) the percentage of p63+ cluster was <30%, (2) the percentage of p63+ single cells in cell clusters was <3%, (3) the number of p63+ single cells in the background was <20 when the total number of the cell clusters was <100, or the number was <120 when the total number was ≥100. The malignant lesions showed significantly lower values than the benign lesions in the percentage of p63+ clusters, the percentage of p63+ single cells in the clusters, and the number of p63+ single cells in the background (P < .001). The diagnostic values obtained only by Papanicolaou staining vs the improved values with LBC-p63 immunostaining slides were as follows. Sensitivity, 88.3% to 99.0%; specificity, 89.1% to 99.0%; positive predictive value, 94.8% to 99.5%; negative predictive value, 77.4% to 97.8%; diagnostic accuracy, 88.6% to 99.0%, respectively. CONCLUSION: The diagnostic accuracy of breast FNAC was significantly improved by adding LBC-p63 immunostaining.

[A Case of Ruptured Peripheral Cerebral Aneurysm at Abnormal Vessels Associated with Middle Cerebral Artery Stenosis:Similarity to Moyamoya Disease].

We report a case of ruptured peripheral cerebral aneurysm at abnormal vessels associated with severe stenosis at the middle cerebral artery (MCA). A 66-year-old woman was admitted at our hospital with headache on foot. Computed tomography (CT) showed intracerebral hemorrhage in the left fronto-basal area. Three-dimensional-CT and conventional angiogram revealed abnormal vessels, which were similar to those seen in moyamoya disease, with a small enhancement close to the hematoma. On day 11, subsequent cerebral angiogram demonstrated an aneurysm at the peripheral portion of an abnormal vessel arising from the left A2. On day 17, soon after the diagnosis of the ruptured aneurysm was made (while still at the subacute stage), we operated on the aneurysm. Superficial temporal artery (STA)-MCA anastomosis was also performed to preserve cerebral blood flow and reduce hemodynamic stress. Several days after the operation, she had transient aphasia due to hyperperfusion of the MCA territory, but eventually recovered with no neurological deficit at discharge. Follow-up study revealed revascularization from the branches of the external carotid artery as well as the STA. On admission, we initially thought that this patient had abnormal vessels associated with arteriosclerotic MCA stenosis. However, the postoperative clinical course as well as the histopathological specimens of both the abnormal artery with the aneurysm and the STA revealed similar findings to those of moyamoya disease. Although this case did not satisfy the criteria for moyamoya disease, it is conceivable that a single arterial occlusive lesion associated with moyamoya-like vessels might develop in the same mechanism with that of moyamoya disease.

Visual assessment of Ki67 using a 5-grade scale (Eye-5) is easy and practical to classify breast cancer subtypes with high reproducibility.

AIMS: Personalised breast cancer therapy requires pathological characterisation of tumours. The proliferative index, based on Ki67, is pivotal, but a standard method has not been established. Here we look for an easy and practical way to evaluate Ki67. METHODS: Immunohistochemical staining of estrogen receptors, progesterone receptors, HER2 and Ki67 (MIB-1) was performed on resected specimens from 406 primary invasive ductal carcinomas. Ki67 labelling index (LI) from manual counting was compared with visual assessment using a 5-grade scale (Eye-5). Next, 10 pathologists evaluated 100 samples with marked hot spots by using Eye-5. Another 100 samples without marking were also assessed by eight pathologists. One year later, two pathologists reviewed 222 cases with Eye-5. Prognosis was analysed among estrogen receptor-positive cases with postoperative endocrine therapy. RESULTS: Eye-5 showed good correlation to LI. All 136 cases of score 4-5 had LI >20% and all 56 cases of score 1 had LI<20%, which means that manual counting was not necessary for about half of the cases. Interobserver and intraobserver variability was low even when a hot spot was not fixed. Eye-5 also correlated with histological grade and lymph node metastasis. Combining Eye-5 and histological grade created a new algorism to predict LI, which allows 80% of all cases (74% of luminal cases) without manual counting. Cases of Eye-5 score 1-2 had significantly better survival than score 3-5. CONCLUSIONS: Visual assessment of Ki67 by a 5-grade scale (Eye-5) is fast, easy, and reliable with acceptably low interobserver and intraobserver variability. Eye-5 can replace LI in many luminal tumours, and is a strong candidate as a standard method of evaluating Ki67.

HER2-Positive Metaplastic Spindle Cell Carcinoma Associated with Synchronous Bilateral Apocrine Carcinoma of the Breast.

Apocrine carcinoma, which is strictly defined as over 90% of tumor cells showing apocrine differentiation, is a rare variant of breast cancer. Here we report an uncommon case in which apocrine carcinomas developed concurrently in both breasts; in addition, a sarcomatoid spindle cell lesion was coincident in the right breast. Both apocrine carcinomas were immunohistochemically negative for estrogen receptor (ER) and progesterone receptor (PgR), but diffusely positive for androgen receptor (AR), GCDFP-15, and HER2. The presence of intraductal components in bilateral carcinomas and the absence of lymph node metastasis suggested that they were more likely to be individual primary lesions rather than metastatic disease. The spindle cell lesion showed a relatively well-circumscribed nodule contiguous with the apocrine carcinoma. HER2 oncoprotein overexpression was observed not only in the apocrine carcinoma, but also in the spindle cell lesion. Since the spindle cell component was intimately admixed with apocrine carcinoma and had focal cytokeratin expression, we diagnosed it as metaplastic spindle cell carcinoma, which was originated from the apocrine carcinoma. To our knowledge, this is the first case report of a patient with synchronous bilateral apocrine carcinomas coinciding with metaplastic carcinoma.

A case of pulmonary mucoepidermoid carcinoma responding to carboplatin and paclitaxel.

A 59-year-old man was admitted to our hospital with dyspnea and cough. A large polypoid tumor was observed in the lower trachea and bronchoscopic polypectomy was performed using a snare to relieve symptoms. The tumor was diagnosed as a high grade mucoepidermoid carcinoma mainly by the histology of piecemeal specimens obtained by bronchoscopic resection. The primary lesion involved the trachea and the main bronchus, and there were multiple metastases in the lung. The patient was treated with the combination of carboplatin and paclitaxel. After four cycles of chemotherapy, the tumors were significantly reduced. He remains well without evidence of tumor progression for 25 months. This case suggests that the combination chemotherapy of carboplatin and paclitaxel can be an option for treatment of pulmonary mucoepidermoid carcinoma.

[Thymic mucosa-associated lymphoid tissue (MALT) lymphoma developing during long-term follow-up for Sjögren's syndrome and idiopathic thrombocytopenic purpura;report of a case].

Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of lymphoma that arises in small CD20-positive lymphocytes. We encountered a case of thymic MALT lymphoma treated with surgical intervention during long-term follow-up for Sjögren's syndrome and idiopathic thrombocytopenic purpura (ITP). Although symptomatic remission of Sjögren's syndrome and ITP had already been achieved, the levels of anti-SSA and anti-SSB antibodies remained high. Chronic stimulation by these antibodies may contribute to the development of MALT lymphoma. A careful follow-up may be indicated for this case with a complex immunological background.

Immunohistochemical and fluorescence in situ hybridization studies on noninvasive and invasive extramammary Paget's disease.

To determine useful immunohistochemical markers for tumor cells in extramammary Paget's disease (EMPD), immunohistochemical (IHC) examinations in 17 patients with EMPD, including 4 patients with dermal invasion, were performed. Among the antibodies examined, cytokeratin 7 (CK7) and CK19 were strongly positive for both intraepidermal and dermally invasive tumor cells in all patients. CAM5.2 and mucin 1 (MUC1) were also good markers. Although IHC examination revealed positive for HER-2 in 4 EMPD patients with dermal invasion, 4 out of 13 noninvasive patients were IHC negative. Fluorescence in situ hybridization (FISH) study revealed negative results for HER-2 gene amplification in 8 IHC positive patients, including each 4 patients of both noninvasive and dermal invasive cases. Our results show that besides CK7, CK19 is another favorable marker of tumor cells of EMPD. Four patients with dermal invasion were strongly positive for HER-2, although negative results were obtained in the FISH study. Further investigations are required to confirm the results of the FISH study.

The role of computer-aided 3-dimensional analytic tools and virtual microscopy in the investigation of radiologic-pathologic correlation.

To cope with recent advances in radiologic imaging technology, a corresponding method for pathomorphologic demonstration should be developed to promote better understanding of radiologic-pathologic correlation. We attempted to obtain gross and microscopic images by using a 3-dimensional analytic tool and virtual microscopy and to link these images with multidetector computed tomography images. Surgically resected specimens were sliced to a thickness of 3 mm, and the digital images of each slice were 3-dimensionally reconstructed with RATOC TRI/3D SRF II software. Histology slides were digitized by using virtual microscopy with an Olympus VS-100. We obtained clear gross pathologic images in arbitrary cut sections of organs, and it was possible to rotate these 3-dimensional images at any angle. Furthermore, we created synchronous cut-section movies of computed tomography and gross pathologic images. Subsequently, we switched from these cut-section movies to virtual microscopy images by clicking on the hyperlink button to observe radiologic-pathologic correlation.

Aneurysms of the renal arteries associated with segmental arterial mediolysis in a case of polyarteritis nodosa.

This is the first report of segmental arterial mediolysis (SAM) accompanied with polyarteritis nodosa (PN), and manifesting aneurysms of the renal arteries. A 73-year-old woman was admitted to hospital because of a high fever. Laboratory tests showed leukocytosis with increased CRP level in the serum. Myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) and proteinase 3 (PR3)-ANCA were negative. There were no signs indicating infection or malignancy. After admission renal function rapidly deteriorated. Treatment was then started with daily oral prednisolone and hemodialysis. On the 40th day of hospitalization the patient suddenly became comatose. Cranial CT showed a subarachnoid hemorrhage. The patient died and an autopsy was performed. The pathological findings showed necrotizing vasculitis of the small arteries in various organs, but not associated with that of arterioles or renal glomerular lesions, indicating PN. Unexpectedly, the segmental arteries of the bilateral kidneys showed vascular lesions of dissecting aneurysms, indicating SAM. This case indicates that SAM is one of the causes of aneurysms in PN and is clinically important when the clinical course of PN patients rapidly advances.

Primitive neuroectodermal tumor of the pancreas.

The primitive neuroectodermal tumor (PNET) of the pancreas, a member of Ewing's sarcoma family of tumors, is extremely rare. We treated a 37-year-old Japanese man who had a solitary pancreatic tumor 40 mm in diameter and multiple hepatic tumors with surgical resection. The PNET was positive for CD99 on immunohistochemical staining. Fluorescence in situ hybridization (FISH) was also performed, which revealed a Ewing sarcoma breakpoint region 1 (EWSR1) 22q12 rearrangement. According to the Japan-Ewing protocol, chemotherapy with Ifomide (ifosfamide), etoposide, vincristine, and cyclophosphamide was given after surgery. To the best of our knowledge, to date 13 PNET cases have been reported with a mean age for all patients of 19.3 years old. Surgical resection was performed in most cases and some patients received postoperative chemotherapy. The clinicopathologic characteristics and management of this extremely rare disease are also discussed.

Primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type: case report and review of the literature.

A primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) is very rare. We found a solitary mass 27 mm in size in the left lobe of the liver of a 58-year-old Japanese man with a history of hepatitis-C infection. Based on the results of imaging studies, the tumor was diagnosed as a hepatocellular carcinoma (HCC). The left lobe of the liver was lobectomized and microscopic findings showed that the tumor was a hepatic MALT lymphoma, while immunohistochemistry showed it to be positive for CD20 and CD79a. In a fluorodeoxyglucose-positron emission tomography examination integrated with computed tomography scanning (FDG-PET CT) before surgery, the tumor was revealed to have a high standardized uptake value (SUV) for FDG. The patient received chemotherapy after surgery. To the best of our knowledge, 45 cases had been reported with a mean age for all patients of 61.4 years. The pathogenesis remains unclear, although half of the patients had a past history of chronic inflammatory liver disease. Surgical resection was performed in most cases and some patients received postoperative chemotherapy or radiotherapy. The clinicopathologic characteristics and management of this extremely rare disease are also discussed.