An autopsy case of progressive multifocal leukoencephalopathy after rituximab therapy for malignant lymphoma.

Progressive multifocal leukoencephalopathy (PML) is a rare fatal demyelinating disease of the central nervous system caused by reactivation of the JC virus (JCV), which is named after the initials of the patient from whom the virus was first isolated. JCV is highly prevalent worldwide, infects humans in early childhood, and the infection persists throughout the course of life in latent form. The present paper deals with the second autopsy case report of rituximab-associated PML in Japan. A 63-year-old woman who had undergone chemotherapy for non-Hodgkin lymphoma developed progressive dysarthria and cerebellar ataxia. Head magnetic resonance imaging (MRI) revealed small, scattered, hyperintense areas in the midbrain, pons and thalamus, and the patient was first diagnosed as having cerebral infarction. Follow-up MRI showed tendency toward cerebellar atrophy and multiple system atrophy cerebellar type was suggested, which we concluded must have coincidentally occurred. It was challenging to perform biopsy due to the location of the foci and the patient's condition. Twelve months later she died of aspiration pneumonia caused by the bulbar lesion. At autopsy, the histological examination suggested the presence of demyelinating foci with numerous foamy macrophages. In the foci, oligodendrocytes with enlarged ground-glass like nuclei were found in a scattered manner and astrocytes with bizarre nuclei were also detected. These findings verified the case as PML. The first diagnosis of cerebral infarction was later withdrawn, although appropriate disorders were not recalled even after testing with various antibodies. The rate of PML development tends to increase after treatment with molecular-targeted therapies, which directly or indirectly attenuate the cellular-mediated immune system. Various novel molecular-targeted and immunosuppressive drugs have been released on the market; the cases of PML have consequently increased. Accordingly, pathologists should keep this disease in mind in the differential diagnosis when neural symptoms newly emerge in patients who are treated with these drugs.

An elderly case of malignant small cell glioma with hemorrhage coexistent with a calcified pilocytic astrocytoma component in the cerebellar hemisphere.

Pilocytic astrocytoma is a less aggressive form of glial tumor that commonly occurs in the pediatric population, and its malignant transformation is extremely rare. Here, we report an elderly case of malignant small cell glioma with hemorrhage coexistent with a calcified pilocytic astrocytoma component. An 80-year-old male was found to have a right cerebellar non-enhanced tumor with hematoma adjoining a calcified nodule. The lesion was surgically removed, and a histological examination verified that the tumor was a malignant small cell glioma with hemorrhagic change and the calcified nodule showed features of pilocytic astrocytoma. Genetic analyses revealed no glioma-relevant genetic alterations such as IDH and BRAF mutations. Although calcification is generally observed in slowly growing gliomas, the aggressive clinical course of calcified cerebellar pilocytic astrocytoma has been previously reported. Our extremely rare case shows that careful follow-up is necessary even for calcified pilocytic astrocytomas.

Predictive factors of biochemical recurrence after radical prostatectomy for high-risk prostate cancer.

OBJECTIVE: To identify risk factors of biochemical recurrence after radical prostatectomy in high-risk patients. METHODS: A total of 191 high-risk prostate cancer patients according to the D'Amico classification treated with radical prostatectomy at a single institution between April 2000 and December 2013 were enrolled. The pathological evaluation including intraductal carcinoma of prostate was reassessed, and the clinical and pathological risk factors of biochemical recurrence were analyzed. RESULTS: The median follow up after radical prostatectomy was 49 months. The 5-year biochemical recurrence-free survival rate after radical prostatectomy in high-risk prostate cancer patients was 41.6%. Initial prostate-specific antigen, pathological Gleason score, seminal vesicle invasion, extraprostatic extension and intraductal carcinoma of the prostate were significantly associated with biochemical recurrence-free survival. The 5-year biochemical recurrence-free survival rates in patients with zero, one, two and three of these risk factors were 92.9%, 70.7%, 38.3% and 28.8%, respectively. In patients with four or more factors, the biochemical recurrence-free survival rate was 6.1% after 18 months. CONCLUSIONS: In D'Amico high-risk patients treated with radical prostatectomy, risk factors for biochemical recurrence can be identified. Patients with fewer risk factors have longer biochemical recurrence-free survival, even among these high-risk cases.

Magnetic resonance imaging manifestations of ovarian mullerian mixed epithelial borderline tumors: imaging and histologic features in comparison with mullerian mucinous borderline tumors.

We illustrate the magnetic resonance imaging features of 3 cases of rare ovarian Mullerian mixed epithelial borderline tumor (MEBT) and identify important diagnostic clues based on their detailed histologic, morphologic, and clinical features. Mullerian mixed epithelial borderline tumor has good prognosis, and adequate management is essential. In order to avoid unnecessary aggressive treatment, radiologists should become familiar with the imaging findings of MEBT. To the best of our knowledge, no articles have described the detailed images of MEBT.

Breast ultrasound elastography and magnetic resonance imaging of fibrotic changes of breast disease: correlations between elastography findings and pathologic and short Tau inversion recovery imaging results, including the enhancement ratio and apparent diffusion coefficient.

PURPOSE: Ultrasound (US) elastography provides information regarding tissue hardness and is expected to become a novel diagnostic tool for breast disease. In contrast, magnetic resonance (MR) images reflect the tissue characteristics. Fibrosis of the stroma of breast diseases may affect their hardness. We investigated the correlation among elasticity score (ES) and signal intensity of short Tau inversion recovery MR images, enhancement ratio, apparent diffusion coefficient (ADC), and the fibrosis in the breast lesions. MATERIALS AND METHODS: We reviewed the findings of US elastography and MR imaging from 41 consecutive patients with breast lesions (25 invasive ductal carcinoma, 3 fibroadenoma, 1 phyllodes tumor, 2 ductal hyperplasia, 2 primary malignant lymphoma, 3 mastopathy, 1 metastasis, 1 tubular adenoma, 1 ductal carcinoma in situ, 1 diabetic mastopathy, and 1 intraductal papilloma). In each patient, elastography images were classified based on Tsukuba ES. We calculated the ratio of signal intensity of the lesion to the muscle on short Tau inversion recovery images (L/M ratio), enhancement ratio of early to precontrast and early to delayed images, and ADC for each lesion. The ES and MR findings were correlated with the degree of fibrosis (based on Masson trichrome stain). RESULTS: The ES significantly correlated with the L/M ratio (P = 0.0306) and the ADC (P = 0.0256). The stromal fibrosis also correlated with ES (P = 0.0023), the L/M ratio (P = 0.0344), and enhancement ratio of the early-to-delayed images (P = 0.049). CONCLUSIONS: The ES and L/M ratio are correlated significantly with each other, and they are correlated with the fibrosis. These results suggest that they will provide the information on the fibrosis and may help the diagnosis of breast lesions.

Breast carcinoma originating from a silicone granuloma: a case report.

Breast carcinoma rarely occurs in cases of foreign body granulomas following liquid silicone injection. Although the Food and Drug Administration (FDA) banned the use of all silicone injection products in 1992, liquid silicone injection for breast augmentation continues to be performed illegally. We herein report a case of breast carcinoma following liquid silicone injection in a 67-year-old female.A total of 45 years after liquid silicone injection, the patient had felt a breast mass in the right breast. Mammography showed a smooth mass that retracted the right nipple. Due to the presence of a marked acoustic shadow caused by the granulomas, evaluating the mass on ultrasonography was difficult. However, magnetic resonance imaging (MRI) showed a lobulated mass under the right nipple. The mass exhibited low signal intensity (SI) on T1-weighted images and intermingled high and low SI on T2-weighted images. Heterogeneous early enhancement with central low intensity was noted on dynamic contrast-enhanced MRI. Several oval-shaped low SI structures in the adipose tissue and disruption of the pectoralis major muscle were also observed. We diagnosed the patient with invasive ductal carcinoma based on a stereotactic-guided Mammotome® (a vacuum-assisted biopsy system manufactured by DEVICOR MEDICAL JAPAN, Tokyo, Japan) biopsy and subsequently performed mastectomy and axillary lymph node dissection (with a positive result for the sentinel node biopsy). Histologically, invasive ductal carcinoma was observed in the silicone granuloma.The development of foreign body granulomas following breast augmentation usually makes it difficult to detect breast cancer; thus, various devices are required to confirm the histological diagnosis of breast lesions. The stereotactic-guided Mammotome® biopsy system may be an effective device for diagnosing breast cancer developing in the augmented breast.

[Distribution of intraductal carcinoma of the prostate and associated lesions in the cancer foci on radical prostatectomy specimens].

OBJECTIVE: The distribution of intraductal carcinoma of the prostate (IDC-P) and other intraductal lesions associated with IDC-P was evaluated in the cancer foci on radical prostatectomy specimens. MATERIALS AND METHODS: We reviewed slide in 412 cases treated by radical prostatectomy without neoadjuvant therapy. Mapping study was performed with regard to IDC-P, other intraductal lesions associated with IDC-P and invasive carcinoma. RESULTS: We identified 98 cases (23.8%) and 102 cancer foci associated with IDC-P. In these all cancer foci, IDC-P was associated with invasive carcinoma and other intraductal neoplastic lesions with tufting, micropapillary and loose cribriform patterns were contiguous and admixed with IDC-P in 83 cancer foci (81.4%). There were lesions with invasive carcinoma around the IDC-P in 95 cancer foci (93.1%) and lesions without invasive carcinoma around IDC-P in 66 foci (64.7%). The latter lesions existed in the marginal areas of the cancer foci in 63 (61.8%) and in the central areas of the cancer foci in 14 (13.7%). In 5 cancer foci (4.9%), volume of IDC-P was larger than that of invasive carcinoma. CONCLUSIONS: The distribution of IDC-P with dense cribriform and solid patterns varied in cancer foci, and intraductal lesions with tufting, micropapillary and loose cribriform patterns were frequently seen in area contiguous and admixed with IDC-P. The latter lesion may be low grade morphology of IDC-P, although the lesions could not be distinguished from high grade prostatic intraepithelial neoplasia.

A case of giant left main coronary artery aneurysm in an elderly man.

Aneurysms of the left main coronary artery are rare and their optimal treatments remain unknown. A 64-year-old man without any symptoms was referred to our department for suspected coronary aneurysm. Transthoracic echocardiography demonstrated an aneurysm of the left main coronary artery. On transesophageal echocardiography, the thrombus was suspected inside and severe ostial stenosis of the left coronary artery was highly suspected due to the accelerated flow velocity. Multidetector computed tomography demonstrated the aneurysm as being 37 mm in diameter with significant stenosis at both left coronary arteries, more clearly than coronary angiography. Because of its size and coexisting coronary artery disease, surgical closure of the aneurysm and coronary artery bypasses were performed. Echocardiography and coronary computed tomography could help in the diagnosis and the therapeutic decision in the case of left main coronary artery aneurysm before coronary angiography.

Lung CT: Part 1, Mimickers of lung cancer--spectrum of CT findings with pathologic correlation.

OBJECTIVE: The purpose of this article is to describe CT findings of miscellaneous pulmonary conditions that mimic lung cancers, especially primary cancers, to improve diagnosis of pulmonary lesions. Brief descriptions of patient clinical information and pathologic findings will be included and correlated with imaging findings in actual cases. CONCLUSION: A wide variety of pulmonary conditions present imaging features that mimic those of primary lung cancers and are difficult to differentiate from cancer. Awareness of these conditions with an understanding of their pathologic background and careful attention to the clinical information will help achieve correct diagnoses.

Huge inflammatory pseudotumor of the spleen with postoperative portal vein thrombosis: report of a case.

We report the rare case of a splenic inflammatory pseudotumor associated with massive splenomegaly, diagnosed after surgery. A 51-year-old woman was admitted to our hospital for investigation of anemia. Physical examination revealed a palpable left upper quadrant mass. Computed tomography and magnetic resonance imaging showed a splenic mass, 20 cm in diameter. We performed splenectomy for both diagnosis and treatment. The spleen weighed 2400 g, and histologic examination of the mass confirmed an inflammatory pseudotumor. Portal vein thrombosis (PVT) developed the day after surgery, but resolved with anticoagulation therapy. This case highlights that there is a risk of PVT after splenectomy in patients with massive splenomegaly, and that anticoagulant therapy should be initiated promptly.

[Liver arterial infusion chemotherapy with adjuvant trastuzumab for the simultaneous treatment of liver and breast cancer-a case report].

A 62-year-old woman being treated for chronic hepatitis C and high blood pressure was shown by computed tomography to have tumors in the lateral and medial segments of her liver, and in her right breast. The tumor in the lateral segment of the liver was excised, the tumor in the medial segment of the liver was treated with microwave coagulation therapy, and the breast tumor was treated with simple mastectomy and sentinel lymph-node biopsy. Based on pathological features, the liver tumors were classified as moderately differentiated liver cell carcinoma, and the breast tumor as estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor-2-positive ductal carcinoma. Hepatic arterial infusion chemotherapy using fluorouracil and cisplatin with trastuzumab as an adjuvant was administered to treat both cancers simultaneously. Twelve months after the operation, neither of the cancers had relapsed. This case suggests that when the breast cancer is human epidermal growth factor receptor-2-positive, trastuzumab should be administered as adjuvant therapy.

Unusual imaging characteristics of cystic meningioma in cerebellopontine angle.

We report a case of cystic meningioma at the left cerebellopontine angle (CPA). Magnetic resonance imaging demonstrated both solid and cystic components in the tumor. The cystic component appeared slightly hyperintense compared to cerebrospinal fluid on fluid-attenuated inversion recovery (FLAIR) imaging. A hypointense tubular structure was identified in the cystic component on 3D driven equilibrium sequencing. These imaging findings are unusual for cystic meningioma. However, awareness of these unusual imaging features is important to determine appropriate treatment strategies although cystic meningioma at the CPA is extremely rare.

Discrepancy in the Ki67 labeling index of brain and orbital metastatic lesions from gastrointestinal neuroendocrine tumors: A case report.

Proliferative activity examined by Ki67 labeling index (LI) plays pivotal role for managing gastrointestinal neuroendocrine tumor (GI-NET). Few reports indicated the intra-patient heterogeneity of Ki67-LI among metastatic tumor sites. We report a case of brain and orbital metastases from GI-NET that showed discrepancy of the Ki67-LI. A 71 year-old woman who was diagnosed as GI-NET with liver and bone metastases and performed medical therapy, had headache, right exophthalmos, and pain of right eye and was referred to our department. Magnetic resonance image revealed that tumors in the left occipital region and right orbit. We diagnosed as metastatic brain and orbital tumors from GI-NET. Surgical removal of both symptomatic lesions was performed and the diagnosis was pathologically confirmed. Immunohistochemical studies revealed the discrepancy of the Ki67-LI of the lesions (brain tumor: 8% versus orbital tumor: 22%). Sampling of multiple metastatic sites may prevent underestimate tumor proliferative activity.

Resection of Pulmonary Metastases 12 Years after Initial Surgery for a Benign Pheochromocytoma.

We describe a rare case of newly discovered pulmonary metastases and surgical confirmation 12 years after initial surgery for a pheochromocytoma. A 61-year-old asymptomatic man was referred because of an abnormal shadow in the right lung field upon chest radiography. Computed tomography (CT) showed two well-demarcated tumors in the basal segment of the right lung. Twelve years previously, he underwent right adrenalectomy and was pathologically diagnosed as having a benign pheochromocytoma. Thereafter, he received a medical check-up annually. To confirm the diagnosis of two pulmonary tumors, video-assisted thoracic surgery was done and wedge resection of the right lower lobe completed. Pathology studies revealed these tumors as pulmonary metastases from the pheochromocytoma, which indicated that the true diagnosis was a malignant pheochromocytoma. Patients with a benign pheochromocytoma should continue to undergo careful monitoring for a long time after the initial surgical procedure. Thoracic surgeons should be aware of the possibility of pulmonary metastases even if >10 years have passed since initial resection of a benign pheochromocytoma.

Thymic basaloid carcinoma with aggressive invasion of the lung and pericardium: report of a case.

We report a case of basaloid carcinoma of the thymus, invading the lung and pericardium. The patient was a 72-year-old man who suffered thoracic trauma in a fall and was taken to his family physician. Computed tomography revealed a huge mediastinal tumor with cystic components, pressing into the lung. He was referred to our hospital, where magnetic resonance imaging showed suspicious invasion of the pericardium and mediastinum. We made an assumed diagnosis of a mediastinal malignancy and performed mediastinal tumor resection. The tumor was adherent to the lung, pericardium, and left innominate vein. The final pathological diagnosis was a basaloid carcinoma of the thymus. Basaloid carcinoma is often a component of a multiloculated thymic cyst (MTC) and should be considered when MTC is identified within an anterior mediastinal tumor.

[A case of pulmonary Langerhans cell histiocytosis with panhypopituitarism].

A 34-year-old woman developed polydipsia, polyuria, amenorrhea and loss of pubic hair in 2001, but did not seek medical advice. On September 7th, 2009, she was admitted to our hospital complaining of acute exacerbation of dyspnea on exertion. Chest computed tomography (CT) showed multiple cystic lesions, predominantly in bilateral lower lung fields. Non-segmental, diffuse ground-glass attenuated areas and thickened bronchovascular bundles were also seen in bilateral lung fields. Pathological findings of lung specimens from a surgical lung biopsy (right S6 and S8) 14 years previously showed infiltration of S100 protein-positive histiocytoid cells in the bronchiolar wall. As a result, pulmonary Langerhans cell histiocytosis (PLCH) was diagnosed. Moreover, panhypopituitarism due to LCH was identified on endocrine testing. Dyspnea on exertion, reduction of carbon-monoxide diffusing capacity (D(LCO)) and ground-glass attenuation areas on CT were improved by smoking cessation alone, and she was discharged. However, similar acute deterioration of PLCH recurred 4 months after first admission. Her dyspnea on exertion, reduction of D(LCO) and ground-glass attenuation areas on CT were improved again by 500 mg/day methylprednisolone pulse therapy for 3 days. This case was a unique combination of panhypopituitarism and the appearance and disappearance of ground-glass attenuation areas on CT, paralleling PLCH disease activity.

Dramatic response to pembrolizumab with chemotherapy followed by salvage surgery in a lung cancer patient.

Immune checkpoint inhibitors with chemotherapy have been shown to exhibit remarkable efficacy for advanced non-small-cell lung carcinoma and are under investigation as an induction therapy. However, the significance of preoperative therapy with pembrolizumab + chemotherapy for surgically resectable non-small-cell lung carcinoma still remains unclear. Here, we report a case of stage IIIB non-small-cell lung carcinoma that underwent salvage surgery after three cycles of pembrolizumab + carboplatin + nab-paclitaxel. Computed tomography revealed the remarkable decrease in tumor volume by 81%. A pathological examination showed that viable neoplastic cells were observed in <1% of the total tumorous lesion suggesting near pathological complete response. This case suggests that this regimen might be a good option as induction therapy for non-small-cell lung carcinoma.

Discrepancy in the Ki67 labeling index of brain and orbital metastatic lesions from gastrointestinal neuroendocrine tumors: A case report.

Proliferative activity examined by Ki67 labeling index (LI) plays pivotal role for managing gastrointestinal neuroendocrine tumor (GI-NET). Few reports indicated the intra-patient heterogeneity of Ki67-LI among metastatic tumor sites. We report a case of brain and orbital metastases from GI-NET that showed discrepancy of the Ki67-LI. A 71 year-old woman who was diagnosed as GI-NET with liver and bone metastases and performed medical therapy, had headache, right exophthalmos, and pain of right eye and was referred to our department. Magnetic resonance image revealed that tumors in the left occipital region and right orbit. We diagnosed as metastatic brain and orbital tumors from GI-NET. Surgical removal of both symptomatic lesions was performed and the diagnosis was pathologically confirmed. Immunohistochemical studies revealed the discrepancy of the Ki67-LI of the lesions (brain tumor: 8% versus orbital tumor: 22%). Sampling of multiple metastatic sites may prevent underestimate tumor proliferative activity.

A deep learning model for the classification of indeterminate lung carcinoma in biopsy whole slide images.

The differentiation between major histological types of lung cancer, such as adenocarcinoma (ADC), squamous cell carcinoma (SCC), and small-cell lung cancer (SCLC) is of crucial importance for determining optimum cancer treatment. Hematoxylin and Eosin (H&E)-stained slides of small transbronchial lung biopsy (TBLB) are one of the primary sources for making a diagnosis; however, a subset of cases present a challenge for pathologists to diagnose from H&E-stained slides alone, and these either require further immunohistochemistry or are deferred to surgical resection for definitive diagnosis. We trained a deep learning model to classify H&E-stained Whole Slide Images of TBLB specimens into ADC, SCC, SCLC, and non-neoplastic using a training set of 579 WSIs. The trained model was capable of classifying an independent test set of 83 challenging indeterminate cases with a receiver operator curve area under the curve (AUC) of 0.99. We further evaluated the model on four independent test sets-one TBLB and three surgical, with combined total of 2407 WSIs-demonstrating highly promising results with AUCs ranging from 0.94 to 0.99.