Miki Izumi

Tokyo Medical University, Edo, Tōkyō, Japan

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Publications (27)51.83 Total impact

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    ABSTRACT: Objectives: To investigate the clinical implication of legumain, an asparaginyl endopeptidase that is highly expressed in several types of cancer, expression in prostate cancer. Methods: Legumain expression in prostate cancer cell lines was determined by real-time reverse transcriptase PCR and Western blot. Furthermore, legumain expression in 88 prostatectomy specimens was evaluated by immunohistochemistry. The association between legumain expression and clinicopathological factors was analyzed. Results: Legumain expression was confirmed at the mRNA and protein levels in all the cells. Although all the cancer tissues were positive for legumain, 2 staining patterns were observed in the cytoplasm: diffuse cytoplasmic and vesicular positivity. The rates of Gleason score ≥8, extracapsular extension, and perineural invasion in the group with vesicular staining were significantly higher than those in the diffuse cytoplasmic group (p < 0.05). The maximum size of the tumor with vesicular staining was significantly greater than that of the tumor with diffuse cytoplasmic staining (p = 0.0302). The 5-year biochemical recurrence-free rate in the patients with vesicular legumain staining was 53.2%; this rate was significantly lower than that (78.8%) in the patients with diffuse cytoplasmic staining (p = 0.0269). Conclusions: Tumors that showed a vesicular staining pattern of legumain had the potential of being highly invasive and aggressive in patients with prostate cancer who were treated with radical prostatectomy. This suggests that legumain might contribute to the invasiveness and aggressiveness of prostate cancer.
    Full-text · Article · Nov 2012 · World Journal of Urology
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    ABSTRACT: A 43-year-old Japanese woman consulted our hospital for a pigmented lesion on her right nipple. Two years later, the lesion became enlarged, measuring 5 × 5 mm. It was dark brown, had an irregular shape and relatively clear borders. Incisional biopsy yielded a pathological diagnosis of junctional nevus of the skin. An additional 2 years later, a small mass developed under the right nipple area and core needle biopsy yielded a pathologic diagnosis of invasive ductal carcinoma. Partial resection of the right EC areas included the skin of the nipple and sentinel lymph node biopsy was performed. Histologically, the skin of the nipple demonstrated small clusters of pigmented carcinoma cells that were low molecular weight cytokeratin (CAM5.2) positive. Most of the carcinoma cells were small and did not have abundant cytoplasm, but nuclear enlargement and prominent nucleoli indicated malignancy, and the cytoplasm was pale compared with that of the surrounding squamous epithelial cells. Scattered dendritic melanocytes were identified by S-100 protein and HMB-45 immunohistochemically. In the upper dermis, carcinoma cells also involved the lactiferous ducts. A small focus of carcinoma cells that invaded the fat tissues did not contain melanin pigment. The final diagnosis was pigmented mammary Paget's disease. Pigmented lesions on the nipple should be carefully examined, because pigmented mammary Paget's disease sometimes mimics malignant melanoma or junctional nevus.
    No preview · Article · May 2011 · Breast Cancer
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    ABSTRACT: A 70-year-old Japanese female noticed a nodule on her back about 6 months before her first visit to our department Clinical examination revealed a 1cm-sized, dark red, movable nodule on her back. There was no evidence of inflammation or infiltration around the nodule. The nodule was initially suspected of being an atheroma, and was excised entirely. Histopathological examination revealed that the tumor had been situated in the deeper dermis to subcutaneous tissue and was composed of spindle cells and mildly atypical round cells. There were no atypical melanocytes in the epidermis. The tumor cells were positive for S-100, c-kit and vimentin, weakly positive for MELAN-A, and strongly positive for p53. The nodule was provisionally diagnosed as a metastatic malignant melanoma, and an expanded resection was performed. Detailed physical examination on the entire skin surface revealed no lesion that suggested a primary melanoma or a resolved melanotic lesion. CT and MRI examinations revealed no tumor lesions in the body. We finally diagnosed the lesion as primary dermal melanoma. There has been no recurrence or metastasis for 18 months following the removal of the tumor.
    No preview · Article · Jan 2011 · Nishi Nihon Hifuka
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    ABSTRACT: Two cases of pediatric orbital rhabdomyosarcoma leading to visual dysfunction with rapid growth. A two-year-old girl who presented with eyelid edema. MRI revealed a tumor in the orbit. The tumor grew rapidly resulting in eye ball displacement and corneal epithelium disorder, and was subsequently removed. Histopathological examination revealed randomly proliferating cells shaped from small round to spindle cells positive for myogenin, desmin and HHF 35 in immunohistochemistry. Based on histopathology and clinical examination, diagnosis of embryonal rhabdomyosarcoma was made. A nine-year-old boy presented with eyelid edema. MRI revealed a tumor under the skin of the upper palpebra extending to the orbit. The tumor grew rapidly to the extent that the eyelids could not be opened spontaneously. Hisitopathologically, spindle-shaped cells were detected proliferating randomly in myxomatous stroma, positive for myogenin and desmin in immunohistochemistry. Based on histopathology and clinical examination, diagnosis of embryonal rhabdomyosarcoma was made. Genetic analysis depicted aberration of chromosome 7 in the first case and tetraploidy in the second case. Both patients subsequently underwent chemotherapy and local radiotherapy and no recurrence has been detected over 1 year. Although rhabdomyosarcoma of the orbit often progresses rapidly and may cause visual disturbances, favorable outcome can be expected by proper management especially in cases with certain histopathological types. A comprehensive approach will be required to elucidate the pathogenesis of orbital rhabdomyosarcoma and genetic abnormalities.
    No preview · Article · Apr 2010 · Nippon Ganka Gakkai zasshi
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    ABSTRACT: Abstract A 54-year-old gentleman was suspected of having sarcoma of the prostate because of his low serum prostate-specific antigen level (1.9 ng/mL) and an enlarged heterogeneous mass on computed tomography and magnetic resonance imaging scans. Pathological examination of the prostate needle biopsy indicated seminoma, which was confirmed with immunohistochemical staining. There was no evidence of disease in other areas on physical examination or on radiographic tests. Therefore, we diagnosed the case as a primary seminoma of the prostate, which was consequently treated with a total of three courses of bleomycin, etoposide and cisplatin chemotherapy. Complete response was obtained on computed tomography, magnetic resonance imaging and prostate needle re-biopsy. To our knowledge, there have only been five cases of primary seminoma of the prostate reported.
    Full-text · Article · Dec 2009 · International Journal of Urology
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    ABSTRACT: Annexin II (ANX2) is a multi-functional protein involved in cell proliferation and membrane physiology and is related to cancer progression. The purpose of this study was to assess ANX2 expression in clear-cell (cc) renal cell carcinoma (RCC). The ANX2 expression in 18 primary ccRCCs was examined by real-time reverse transcriptase (RT)-PCR and western blot analyses. Furthermore, immunohistochemical study was performed using paraffin section of 154 primary ccRCCs and 24 metastases. The association between ANX2 expression and the clinicopathological factors and prognosis was analysed. The ANX2 was upregulated at both mRNA and protein levels in 14 of 18 primary ccRCCs. Immunohistochemical analysis showed that ANX2 was positive in 73 (47.4%) of 154 primary ccRCC and in 21 (87.5%) of 24 metastatic tumours. The ANX2 expression in the primary tumours showed significant associations with a higher stage, a higher nuclear grade. In patients without metastasis, the 5-year metastasis-free rate in patients with ANX2-positive tumour was significantly lower than that in those with ANX2-negative tumour (63.0% vs 90.1%; P<0.0001). Multivariate analysis showed that ANX2 expression is an independent predictor for metastasis. Our findings suggest that ANX2 expression might be a novel predictor of the metastatic potential of ccRCC.
    Preview · Article · Jun 2009 · British Journal of Cancer
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    ABSTRACT: Several ETS transcription factors, including ELF4/MEF, can function as oncogenes in murine cancer models and are overexpressed in human cancer. We found that Elf4/Mef activates Mdm2 expression; thus, lack of or knockdown of Elf4/Mef reduces Mdm2 levels in mouse embryonic fibroblasts (mef's), leading to enhanced p53 protein accumulation and p53-dependent senescence. Even though p53 is absent in Elf4−/− p53−/− mef's, neither oncogenic H-RasV12 nor c-myc can induce transformation of these cells. This appears to relate to the INK4a/ARF locus; both p19ARF and p16 are increased in Elf4−/− p53−/− mef's, and expression of Bmi-1 or knockdown of p16 in this context restores H-RasV12-induced transformation. Thus, ELF4/MEF promotes tumorigenesis by inhibiting both the p53 and p16/Rb pathways.
    Full-text · Article · May 2009 · Molecular and Cellular Biology
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    ABSTRACT: Although nevus sebaceus is known to develop various types of secondary neoplasms, it rarely causes carcinoma and only 14 cases of secondary sebaceous carcinoma have been reported. In this study, 10 cases of sebaceous carcinoma arising in nevus sebaceus were collected. The clinicopathological features and results of immunohistochemical examinations with adipophilin, perilipin and p53 were summarized. Sebaceous carcinoma arising in nevus sebaceous predominantly occurred on the scalp (8/10) of elderly women (mean age, 67.7 years). No case was associated with Muir-Torre syndrome. We found several pathological features of sebaceous carcinoma; that is, made up mainly of germinative cells, moderate nuclear atypia without pleomorphism and many mitoses (4-28/10 high-power field). Adipophilin and perilipin antibodies highlighted lipid drops in the cytoplasm of the malignant cells in all cases. Overexpression of p53 was seen in all cases. In two cases there were coexisting benign-looking sebaceous lesions at the periphery of the main cancer nodule, and in these lesions p53 showed low positivity compared with the clearly malignant area. There was co-occurrence of another neoplasm in three cases with trichoblastoma, sebaceoma and syringocystadenoma papilliferum, respectively. All cases were treated by excision of the malignant lesion, with or without inclusion of the nevus sebaceus. In a follow-up period of 1-7 years, there was no case of recurrence, lymph node metastases or distant metastases. With these specific pathological and immunohistochemical findings using adipophilin, perilipin and p53, we have to consider the possibility that there is a tendency to underdiagnose secondary sebaceous carcinomas in nevus sebaceus. These clinicopathological features of sebaceous carcinomas developing in the nevus sebaceus seem to indicate different biological entities from de novo sebaceous carcinoma.
    No preview · Article · Dec 2008 · The Journal of Dermatology
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    ABSTRACT: A 35-year-old man was admitted with continuous general fatigue and low grade fever. He was HIV-positive, and had gastric diffuse large B-cell lymphoma and renal T-cell anaplastic large cell lymphoma (T-ALCL). We diagnosed double lymphomas related to AIDS. The patient received anti-retroviral therapy, and started the CHOP regimen for the double lymphomas, resulting in transient improvement. However, fever again appeared during HAART and CHOP treatment, and a right inguinal subcutaneous lesion appeared. Biopsy specimen demonstrated null cell ALCL, and this patient demonstrated multiple lymphomas. This case suggested that cancer generation was promoted by low immunity, although it is known that ambivalent tumors such as non-Hodgkin lymphomas can occur frequently.
    No preview · Article · Dec 2008 · [Rinshō ketsueki] The Japanese journal of clinical hematology
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    ABSTRACT: Subungual melanoma is a rare form of malignant melanoma. It is extremely difficult to differentiate it histologically from benign melanonychia striata or melanocytic nevus, especially in the early stage. We divided 50 cases of subungual melanoma into four groups according to clinical progress, and examined their histological findings in each respective stage. In the early stage (19 cases), atypical melanocytes were polygonal showing slight nuclear atypia with no mitoses at all. In six out of 19 cases (31.6%), the atypical melanocytes proliferated more in the hyponychium than in the nail matrix, and only very few in the nail bed. Periungual pigmentation (Hutchinson's sign) appeared from the early stage in almost all cases. With stage progression (middle stage, 13 cases; progressive stage, 13 cases; and bone invasive stage, five cases) the number of atypical melanocytes and their degree of nuclear atypia increased, and the ascent of atypical melanocytes and pagetoid spread became conspicuous. Mitoses became apparent only from the progressive stage. From these observations, we would like to propose three new pathological clues of early stage subungual melanoma: (i) "skip lesion", proliferation of the tumor cells are more prominent in the hyponychium than in the nail bed or nail matrix; (ii) histological confirmation of Hutchinson's sign; and (iii) epithelial thickening and/or compact arrangement of the elongated basal cells.
    No preview · Article · Dec 2008 · The Journal of Dermatology
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    ABSTRACT: Tenascin-C is an extracellular matrix protein that plays an important role in cell proliferation, migration and tumor invasion in various types of cancer. However, few reports exist on tenascin-C expression in renal cell carcinoma (RCC). This study aimed to assess the prognostic significance of tenascin-C in clear cell RCC. Using immunohistochemistry, 137 formalin-fixed, paraffin-embedded tissue sections obtained from patients with clear cell RCC were examined for tenascin-C expression. Tenascin-C expression was observed in 55 (40.1%) of the 137 clear cell RCC sections. Tumor cells displayed membranous and/or cytoplasmic staining for tenascin-C. Tenascin-C expression was more prominent near the pseudocapsule of the tumor and around the tumor vessels. Tenascin-C expression was significantly associated with a higher stage (P=0.0065) and higher nuclear grade (P=0.0001). However, there was no correlation between the tenascin-C expression and venous involvement. The cancer-specific survival rate in patients with a tenascin-C-positive primary tumor was significantly lower than that in those with a tenascin-C-negative primary tumor in univariate analysis (P=0.0017). However, tenascin-C expression did not exhibit a significant value for cancer-related death in the Cox regression analysis. In patients with stage 1-3 disease, the 5-year metastasis-free rate in patients with the tenascin-C-positive primary tumor was significantly lower than that in those with the tenascin-C-negative primary tumor (67.8 vs. 88.5%, respectively; P=0.0038). The Cox regression analysis showed that tenascin-C expression is a significant predictor of metastasis (P=0.0345). The tenascin-C expression was strongly related to the stage, nuclear grade and 5-year metastasis-free rate. Therefore, tenascin-C expression may be a possible marker for the metastatic potential of clear cell RCC.
    No preview · Article · Oct 2008 · Oncology Reports
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    ABSTRACT: Despite recent advances in molecular biology that have clarified the mechanisms involved in the metastasis of several types of cancer, the molecular mechanism underlying the metastasis of renal cell carcinoma (RCC) remains unclear. Two RCC cell lines were successfully established from the surgical specimens of a matched primary tumor and adrenal metastasis from the same RCC patient, and were designated as TMK-1P and TMK-1M, respectively. Extensive characterization was accomplished using various methods, including the Matrigel invasion assay, DNA microarray analysis and real-time reverse transcriptase (RT)-polymerase chain reaction (PCR). While TMK-1P grew faster than TMK-1M, the invasive ability of TMK-1M was higher than that of TMK-1P. DNA microarray analysis showed a large differential expression of genes related to cell adhesion and the extracellular matrix molecules of which hexabrachion (tenascin-C), epidermal growth factor receptor, cadherin-6, and beta1-catenin were down-regulated, and the 67 kDa laminin receptor 1 and transforming growth factor-beta-induced 68 kDa protein (betaig-h3) were up-regulated in TMK-1M. Real-time RT-PCR analysis confirmed this differential gene expression between the two cell lines. The RCC cell lines may be useful in studying tumor invasion and screening markers for metastasis.
    Full-text · Article · Oct 2008 · Oncology Reports
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    ABSTRACT: Sebaceous carcinoma of the eyelids is rare in Western countries but not uncommon in Asian countries. Diagnosis is difficult both clinically and histologically. Thirty cases of sebaceous carcinoma of the eyelids treated at Tokyo Medical University Hospital were reviewed to elicit characteristic features of pathological findings. The tumor cells were infiltrating in a lobular pattern that consisted mainly of large atypical germinative cells. Sebocytes seen in the lobules had conspicuous nucleolus associated with perinucleolar halo. In 17 cases (57%) there was foamy histiocyte infiltration in and around the tumor nests. Sebaceous duct differentiation, namely holocrine secretion indicating a specific type of coagulation necrosis maintaining a cellular framework or maintaining a bubbly cytoplasm associated with nuclear debris in the periphery, was seen in 24 cases (80%). Although unequivocal squamous differentiation was limited to only 11 carcinomas, scattered individual necrosis with nuclear debris in the background of germinative cells appeared in 29 cases (96.7%). Expression of epithelial membrane antigen, perilipin and adipophilin were detected in all cases. In conclusion, to detect sebaceous differentiation in sebaceous carcinoma, it would be helpful to focus on holocrine secretion, squamous differentiation and foamy macrophage infiltration, and to utilize immunohistochemistry involving anti-perilipin and anti-adipophilin stain.
    No preview · Article · Sep 2008 · Pathology International
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    ABSTRACT: Epithelial-myoepithelial carcinoma (EMC) of the salivary glands is an uncommon, low-grade malignant tumor. A recent report demonstrates sebaceous differentiation in this tumor even though its significance has never been documented as a precise histologic variant. Six cases of EMC exhibiting sebaceous differentiation (sebaceous EMC) of the parotid gland were analyzed for their clinicopathologic features and immunohistochemical characteristics. In addition, primary salivary sebaceous carcinomas were also examined for comparison. In our series, the incidence of sebaceous EMC was 0.2% among 3012 cases of parotid gland tumors and 14.3% of all EMC cases. The 6 patients comprised 2 men and 4 women, age ranging from 77 to 93 years (mean, 83.7 y). Neither cervical lymph node nor distant organ metastases were found in any cases of sebaceous EMC and no patients died of disease, though local recurrences developed in 1 patient. Conversely, cervical lymph node metastasis was detected in 2 of 3 patients with sebaceous carcinoma, 1 of whom died of disease at 12 months. Histologically, all 6 tumors had an area of sebaceous differentiation admixed with features of bilayered ductal structures typical of EMC. A component of sebaceous differentiation was distributed diffusely in 4 tumors and focally in 2. Cytologic atypia of sebaceous EMCs was lesser than that of sebaceous carcinomas. Immunohistochemically, putative myoepithelial markers such as α-smooth muscle actin, calponin, p63, cytokeratin 14, S-100 protein, and vimentin were highly expressed in sebaceous EMC. However, the expression of the latter 4 markers was also observed in primary sebaceous carcinomas, whereas these tumors were all negative for α-smooth muscle actin and calponin. Positive immunoreactivity for epithelial membrane antigen, adipophilin, and perilipin confirmed sebaceous differentiation in EMC. These results indicate that sebaceous EMC is a low-grade malignancy, similar to conventional EMC. Our data also suggest that immunohistochemical examination of specific myoepithelial markers is helpful in distinguishing sebaceous EMC from sebaceous carcinoma, which may occasionally be associated with an aggressive clinical course.
    No preview · Article · May 2008 · American Journal of Surgical Pathology

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  • No preview · Article · Jan 2008
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    ABSTRACT: Directed movement of normal cells occurs when actin-related protein 2 and 3 complex (Arp2/3 complex) triggers the actin polymerization that forms lamellipodia immediately after binding to WAVE2. In order to determine whether the same mechanism correlates with liver metastasis from colorectal cancer, paired mirror sections of 154 cancer specimens (29 cases with liver metastasis and 125 cases without liver metastasis in which T factor, gender, primary tumor site, and age at operation were matched) were examined immunohistochemically for the localization of Arp2 and WAVE2. Expression of both Arp2 and WAVE2 was detected in the same cancer cells in 55 (35.7%) of the 154 cases, but not detected in the normal colonic epithelial cells. Univariate analysis showed that the colocalization was significantly predictive of liver metastasis (risk ratio [RR] 8.760. Likewise, histological grade (RR 2.46), lymphatic invasion (RR 9.95), and tumor budding (RR 4.00) were significant predictors. Among these, colocalization and lymphatic invasion were shown to be independent risk factors by multivariate analysis. Another 59 colorectal specimens were examined for mRNA expression of Arp2 by real time polymerase chain reaction. High mRNA levels of Arp2, that in situ hybridization revealed to be expressed by the cancer cells, were significantly associated with liver metastasis. However, its effect was absorbed by the influence of risk of the colocalization that is closely related to high expression of Arp2. These results indicate that the colocalization of Arp2 and WAVE2 is an independent risk factor for liver metastasis of colorectal carcinoma. (Cancer Sci 2007; 98: 992–999)
    Full-text · Article · Apr 2007 · Cancer Science
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    ABSTRACT: We report a case of dedifferentiated liposarcoma of the spermatic cord that produced a widely infiltrative local recurrence. A 44-year-old man was referred to Tokyo Medical University Hospital with a diagnosis of inguinal hernia. Preoperative computed tomography and an echogram revealed a tumor in the groin. Postoperativly, the patient was followed on an outpatient basis. However, the patient did not return to the clinic for approximately fours years. Upon re-examination a recurrent, tumor was recognized in the left groin. Computed tomography revealed a tumor in the periphery of the external iliac artery. During surgery, the tumor was found to have infiltrated a wide area. Invasion to the sigmoid colon, left ureter, external iliac artery and vein, and to the bladder wall was noticed. The initial and recurrent tumor consisted partially of well differentiated liposarcoma and mostly of spindle cells with various degrees of atypia. Accordingly, a diagnosis of dedifferentiated liposarcoma was made. The patient's condition improved after surgery, and he has been free of recurrence for 3 years since the operation.
    No preview · Article · Mar 2007 · Nippon Shokaki Geka Gakkai zasshi
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    ABSTRACT: A 64 year-old-male with a red tumor on his head, visited our hospital. The patient had suffered injury to his head at the age of 15. When he was 20 years old, he noticed a small nodule on his head, coinciding with the site of the injury, which was then resected. Subsequently, the nodule reappeared and has been increasing gradually in size from the age of 40. The clinical appearance consisted of a pediculated red tumor, 46 x 48 x 11mm in size, showing signs of erosion on the surface in his parietal field. The tumor was excised subsequent to the biopsy. Pathologically, the tumor nests consisted of small, uniform, cuboidal poroid cells with differentiation to the sweat duct were proliferated. Although the border with the normal tissue was relatively clear, in deeper areas the tumor nest, characterized by slight nuclear atypia, had infiltrated into the dermis. This tumor was diagnosed as a "low grade porocacinoma".
    No preview · Article · Jan 2007 · Nishi Nihon Hifuka
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    ABSTRACT: A 35-year-old woman was admitted to our hospital because of an abnormal chest radiograph. Chest X-ray on admission showed multiple small nodular shadows in both lung fields but no bilateral hilar lymphadenopathy (BHL). Moreover, abdominal CT showed some nodules in the liver and spleen, and serum ACE was slightly increased to 23.3U/L (normal range: 8.3-21.4U/L). Transbronchial lung biopsy and liver biopsy resulted in a diagnosis of stage III pulmonary sarcoidosis with hepatosplenic disease. Histopathological findings demonstrated non-caseating epithelioid cell granulomas with giant cells in both specimens. Interestingly, propionibacterium acnes (P. acnes), the possible pathogen of sarcoidosis, was detected in giant cells in the lung and epitheliod cell granuloma of liver tissue. This case was of interest considering P. acnes might have been the causative pathogen.
    No preview · Article · Oct 2006