Annals of Diagnostic Pathology RSS feed: Current Issue. A peer-reviewed journal devoted to the publication of articles dealing with traditional morphologic studies using standard diagnostic techniques and stressing clinicopathological correlations and scientific observation of relevance to the daily practice of pathology. Special features include pathologic-radiologic correlations and pathologic-cytologic correlations.http://www.annalspathology.com/?rss=yesElsevier Inc.en © 2009 Published by Elsevier Inc. All rights reserved. Annals of Diagnostic Pathology1092-9134141February 2010 © 2009 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.annalspathology.com/article/PIIS1092913409001579/abstract?rss=yesEditorial Board10.1016/S1092-9134(09)00157-9Annals of Diagnostic Pathology 14, 1 (2010)2010-02-01Annals of Diagnostic Pathology2010-02-01141S1092-9134(09)X0007-9IFCIFChttp://www.annalspathology.com/article/PIIS1092913409000550/abstract?rss=yesAbstract: Apocrine metaplasia (APM) is a common finding in the breast of postmenopausal women and is seen in a broad spectrum of lesions ranging from microscopic cysts to invasive apocrine carcinoma. Apocrine metaplasia within sclerosing adenosis is known as apocrine adenosis (AA) and is considered a benign lesion of the breast. Apocrine metaplasia and AA have been the subject of many studies; however, little is known about the dynamics of cell turnover in these lesions. Recent studies have shown that some forms of AA may show altered degree of proliferation along with altered expression of bcl-2 and bax proteins. In the current study, we investigate further aspects of apoptosis to help understand the mechanisms of cell turnover in AA and APM. To investigate cell turnover in APM and AA, immunohistochemistry was used to study the expression of the apoptotic markers Bak, Mcl-1, Bcl-x, and Bcl-xL in 45 cases of APM (13 cases of nonpapillary APM, 21 cases of simple papillary APM, and 11 cases of complex papillary APM). Also, 34 cases of AA (23 cases of non–atypical AA [NAA] and 11 cases of atypical AA [AAA]) were included in the study. The expression of hTERT and the proliferation marker Ki-67 were also determined. The TdT-mediated dUTP nick-end labeling (TUNEL) technique was used to study the apoptotic status in 28 cases of APM (12 cases nonpapillary APM and 16 cases of papillary APM including simple and complex forms) and 22 cases of AA (15 cases of NAA and 7 cases of AAA). The results showed that all cases studied by immunohistochemistry were positive for the expression of Bak, Mcl-1, Bcl-x, and Bcl-xL showing a pattern of staining similar to that seen in the normal breast epithelium. There was no relation between hTERT positivity and the degree of proliferation in any of the lesions studied. The TUNEL results revealed an apoptotic index (AI) of 0.4% and 0.2% in the papillary and nonpapillary groups of APM, respectively. There was no statistical significance between the AI of these 2 groups and that of the normal breast epithelium (0.3%). The average Ki-67 index in the nonpapillary group was 0.7%, whereas in the papillary group, a value of 4% was recorded. In the cases of AA, an AI of 0.4% and 0.3% in NAA and AAA, respectively, was seen. There was no statistical significance between the AI of these 2 groups and that of the normal breast epithelium (0.3%). The Ki-67 index was 5.2% and 6.6% in the NAA and AAA, respectively. The current results show that apoptosis is not a common event in APM and AA even in the presence of increased proliferation, which may render some of these lesions more susceptible to oncogenic changes. Further studies are needed to study other apoptotic pathways that may be involved in cell turnover in these lesions.Cell turnover in apocrine metaplasia and apocrine adenosis of the breastGhada Elayat, Abdel-Ghani A Selim, Clive A Wells10.1016/j.anndiagpath.2009.05.001Annals of Diagnostic Pathology 14, 1 (2010)2010-02-01Annals of Diagnostic Pathology2010-02-01141S1092-9134(09)X0007-9Original Contributions17http://www.annalspathology.com/article/PIIS1092913409001099/abstract?rss=yesAbstract: Mesenchymal chondrosarcoma is a rare malignant tumor in the differential diagnosis of other small, round blue cell tumors, including atypical teratoid tumor in the central nervous system (CNS) and rhabdomyosarcoma in the musculoskeletal (MSK) locations. We reviewed the morphology of CNS and MSK cases and applied a panel of immunostains. Archival cases were pulled from our files. Immunohistochemistry and follow-up were obtained. Twenty-two cases included 5 CNS (all female; mean age, 30.2) and 17 MSK (11 female and 6 male; mean age, 31.1). Both CNS and MSK examples had similar round cells, staghorn vascular pattern, increased mitotic activity, and centrally located hyaline cartilage islands. The CNS examples demonstrated more spindling and the MSK cases more necrosis. INI1 was retained in all tumors studied. Epithelial membrane antigen (EMA) and desmin were expressed focally in 35% and 50% of cases, respectively. The round cells of all cases were negative for MyoD1, myogenin, smooth muscle actin (SMA), glial fibrillary acid protein (GFAP), keratins, and estrogen receptor, as well as a panel of other antiobodies. Eighty percent of patients with follow-up had pulmonary metastases and/or died within a mean of 5 years. The CNS and MSK mesenchymal chondrosarcoma predominantly affects adult females with poor prognosis. There are only subtle morphologic differences between the CNS and MSK groups. By immunohistochemistry, mesenchymal chondrosarcoma occasionally expresses aberrant desmin and EMA but is negative for SMA, myogenin MyoD1, GFAP, and keratins, refuting true smooth or skeletal muscle, epithelial, or meningothelial phenotype. Retained INI1 separates these tumors from atypical teratoid tumor. Despite marked female predominance in our series, estrogen receptor is negative in mesenchymal chondrosarcoma.Immunoprofile of mesenchymal chondrosarcoma: aberrant desmin and EMA expression, retention of INI1, and negative estrogen receptor in 22 female-predominant central nervous system and musculoskeletal casesJulie C. Fanburg-Smith, Aaron Auerbach, Jayson S. Marwaha, Zengfeng Wang, Mariarita Santi, Alexander R. Judkins, Elisabeth J. Rushing10.1016/j.anndiagpath.2009.09.003Annals of Diagnostic Pathology 14, 1 (2010)2009-12-09Annals of Diagnostic Pathology2009-12-09141S1092-9134(09)X0007-9Original Contributions814http://www.annalspathology.com/article/PIIS1092913409001117/abstract?rss=yesAbstract: Cutaneous angiosarcoma (AS) is a rare malignant neoplasm of dermis composed of infiltrating cells of endothelial phenotype with overall poor prognosis. Although autocrine stimulation by vascular endothelial growth factor secretion may play a role in the pathogenesis of angiosarcoma, its mechanism has not been fully established. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that mediates cellular and systemic homeostatic responses to hypoxia.. The stability of HIF can regulate key proteins in angiogenesis and the α-subunit has been found in epithelial tumors, only 1 case of human retroperitoneal angiosarcoma, and rare vascular proliferations and tumors in knockout mice. We wanted to observe the utility of HIF-1α as a marker or explanatory factor in AS. Cases coded as “angiosarcoma” of dermis were culled and re-reviewed for inclusion as AS, based on patient folder, slides, and obtained immunohistochemistry including CD31 and smooth muscle actin (SMA). Hypoxia-inducible factor-1α was performed on a subset of cases, with additional available material. Forty-five cases met the criteria for AS; there were 17% females and 83% males, with a mean age at presentation of 67 years (range, 27-88 years). Tumors presented most commonly in the skin of the scalp followed by the left lower leg, face, nose, lower arm, neck, thigh, eyelid, ear, and temple. Associated basal cell carcinoma was noted in 1 patient; no others had other neoplasms or unrelated surgeries. There was no history of other primary, lymphedema, radiation, breast-associated, or thorotrast-induced angiosarcoma. The tumors ranged in size from 0.4 up to 9.5 cm, with a mean size of 2.4 cm. Histopathologically, most tumors were vasoformative, with either solid architecture (n = 35) or papillary endothelial hyperplasia-like foci (n = 7). All cases demonstrated infiltrative growth pattern, cytologic atypia, and mitotic activity, including atypical forms. Surface ulceration was present in 44% and solar elastosis in the most evaluable cases. Epithelioid morphology was present in 29% (n = 13) cases. Mild to moderate lymphocytic inflammatory response was noted in 62% (n = 28) cases. CD31 highlighted malignant endothelial cells. SMA (for pericytes) was generally absent. Hypoxia-inducible factor 1α was focally positive in cytoplasm of 3 of 18 (17%) cases studied. Treatment and follow-up data were only available on 4 cases: 2 died of disease within 4 years, 2 others had known recurrence within 2 years. Cutaneous angiosarcoma is largely found on the scalp of older individuals. Requirement for diagnosis includes extravascular proliferation of atypical endothelial cells with mitotic activity in vasoformative, solid, and papillary patterns. Absence of SMA can prove extravascular extension of tumor, outside their normal vessel confines. Cutaneous angiosarcoma generally lacks HIF-1α expression. Accordingly, the hypoxic response pathway is not thought to be a documentable common mechanism of angiogenesis in this entity.Sporadic cutaneous angiosarcomas generally lack hypoxia-inducible factor 1α: a histologic and immunohistochemical study of 45 casesMalak Abedalthagafi, Elisabeth J. Rushing, Aaron Auerbach, Mohamed M. Desouki, Jason Marwaha, Zengfeng Wang, Julie C. Fanburg-Smith10.1016/j.anndiagpath.2009.09.005Annals of Diagnostic Pathology 14, 1 (2010)2009-12-11Annals of Diagnostic Pathology2009-12-11141S1092-9134(09)X0007-9Original Contributions1522http://www.annalspathology.com/article/PIIS1092913409001233/abstract?rss=yesAbstract: This study was conducted to clarify whether or not expressions of hypoxia-related molecules would have clinicopathological significance in squamous cell carcinoma (SCC) of the esophagus. Expressions of hypoxia inducible factor-1 alpha (HIF-1α), glucose transporter 1 (GLUT-1) and RAC-1 were immunohistochemically analyzed in 96 surgically resected SCCs at pT1b (sm1, 12 cases; sm2, 35 cases; sm3, 49 cases). They were divided into a lymph node metastasis (LNM)–positive group composed of 44 cases and an LNM-negative group composed of 52 cases. Immunohistochemical profiles were estimated based on the staining extent (score: 1+, 2+, 3+) and intensity (score: 1+, 2+, 3+). A significant expression pattern was found in the nucleus for HIF-1α, cell membrane for GLUT-1 and cytoplasm for RAC-1. The cases were categorized into a high score group (total score of 4 or more) and a low score group (total score of 3 or less) in each maker, respectively. A comparison made between the LNM-positive group and the LNM-negative group showed that the proportion of cases with a high score was larger in the LNM-positive group than in the LNM-negative group (HIF-1α, P = .02; GLUT-1, P = .008; RAC-1, P = .001). Among them, HIF-1α was found to be significantly related to the disease-free survival (P = .019) and overall survival (P = .034) as well as LNM (disease-free survival, P = .030; overall survival, P = .030). The multivariate analysis demonstrated that the HIF-1α expression would be an independent indicator for prognosis. In the superficial SCCs of the esophagus, GLUT-1 and RAC-1 may be involved in LNM, and HIF-1α overexpression is expected to predict an unfavorable clinical outcome.Clinicopathological implications of expressions of hypoxia-related molecules in esophageal superficial squamous cell carcinomaNaoki Ogane, Masanori Yasuda, Michio Shimizu, Masaki Miyazawa, Shingo Kamoshida, Akiko Ueda, Ken Takata, Yuji Sakuma, Yohei Miyagi, Yoichi Kameda10.1016/j.anndiagpath.2009.10.003Annals of Diagnostic Pathology 14, 1 (2010)2010-02-01Annals of Diagnostic Pathology2010-02-01141S1092-9134(09)X0007-9Original Contributions2329http://www.annalspathology.com/article/PIIS1092913409001385/abstract?rss=yesAbstract: We described 2 cases of plasmacytoma presenting with a preponderant involvement of the pleural membranes simulating clinically, radiologically, and on gross pathologic inspection a primary mesothelioma. The patients were an 80-year-old man and a 45-year-old woman. In both cases, the clinical presentation was that of a serosal tumor, including effusions and pleural thickening. In the former, the serosal infiltration raised the suspicion of mesothelioma reinforced by history of occupational exposure to asbestos. Patient general condition deteriorated rapidly. Postmortem examination revealed unilateral encasing of the lung within a thick, irregular neoplastic rind. In addition, tumoral involvement was seen in the homolateral third rib and the clavicle. Histologic examination of pleural masses demonstrated diffuse infiltration by highly atypical, pleomorphic plasma cells with κ chain restriction. In the second case, clinical presentation was also suspicious of mesothelioma. Nonetheless, a pleural biopsy specimen showed irregular sheets of plasma cells showing κ light chain restriction. A bone marrow aspirate was also positive for abnormal plasma cell infiltrates. Despite chemotherapy, the patient died 4 months after presentation. Although rarely, it seems that plasmacytoma may present with an exclusive or preponderant pleural involvement; and it may therefore be added to the list of pseudomesotheliomatous tumors.Plasma cell myeloma presenting with diffuse pleural involvement: a hitherto unreported pattern of a new mesothelioma mimickerAntonio Colonna, Gabriela Gualco, Carlos E. Bacchi, Marcia Araujo Leite, Maurizio Rocco, Giovanna DeMaglio, Stefano Pizzolitto, Giovanni Falconieri10.1016/j.anndiagpath.2009.10.005Annals of Diagnostic Pathology 14, 1 (2010)2010-02-01Annals of Diagnostic Pathology2010-02-01141S1092-9134(09)X0007-9Original Contributions3035http://www.annalspathology.com/article/PIIS1092913409001105/abstract?rss=yesAbstract: Juvenile xanthogranuloma is a relatively rare cutaneous tumor of histiocytic origin, occurring mainly in neonates, children, and young people in the first 2 decades of life. An occurrence in adults is rare. Very rare is also a “deep“ subcutaneous and intramuscular localization of this tumor that is called in such case as “deep juvenile xanthogranuloma.” A very uncommon variant of this tumor is the so-called mitotically active xanthogranuloma, which was described in the literature only in a single case. We present an interesting case of the mitotically active intramuscular juvenile xanthogranuloma of the upper arm in a 28-year-old woman. Before surgical excision, the tumor was examined by fine-needle aspiration biopsy. A diagnosis of deep malignant melanoma or alveolar rhabdomyosarcoma was considered. One year after the total excision, the patient is free of disease. In the presented case, we emphasize cytologic-histologic correlation. In the differential diagnosis, we considered especially an atypical diffuse giant cell tumor of tendon sheaths and joints (extra-articular pigmented villonodular synovitis) and some rare types of soft tissue leiomyosarcoma, such as epitheloid leiomyosarcoma and leiomyosarcoma with prominent osteoclast-like giant cells.Mitotically active deep juvenile xanthogranulomaJan Koren, Ludovit Matecek, Michal Zamecnik10.1016/j.anndiagpath.2009.09.004Annals of Diagnostic Pathology 14, 1 (2010)2009-12-11Annals of Diagnostic Pathology2009-12-11141S1092-9134(09)X0007-9Cytologic-Pathologic Correlations3640http://www.annalspathology.com/article/PIIS1092913409000379/abstract?rss=yesAbstract: Anaplastic transformation of papillary thyroid carcinoma is a rare condition and is associated with an aggressive behavior. Most cases described in the literature have occurred in the thyroid gland or in the surrounding cervical lymph nodes. We report a case of an 83-year-old man who, 10 years after being treated for a conventional papillary thyroid carcinoma, presented with widespread metastases in his lungs. At autopsy, he was found to have extensive metastatic deposits in both lungs, which histologically and immunohistochemically were consistent with papillary thyroid carcinoma. An unusual finding was the presence of solid pleomorphic foci within tumor deposits, consistent with anaplastic transformation.Anaplastic transformation in lung metastases of differentiated papillary thyroid carcinoma: an autopsy case report and review of the literatureWael Al-Qsous, Iain D. Miller10.1016/j.anndiagpath.2009.04.003Annals of Diagnostic Pathology 14, 1 (2010)2009-05-25Annals of Diagnostic Pathology2009-05-25141S1092-9134(09)X0007-9Case Reports4143http://www.annalspathology.com/article/PIIS1092913409000380/abstract?rss=yesAbstract: Desmoplastic spindle cell tumor of the liver is a recently described and extremely unusual neoplasm that affects children and young adults. We report 1 case in a 33-year–old man. The patient had abdominal pain and dyspepsia. Abdominal examination showed that the liver was enlarged and palpable until umbilical region. Laboratory studies demonstrated positive serologic markers to hepatitis B virus. All other analytical studies were irrelevant. Computed tomography revealed a large tumor mass in left hepatic lobe showing heterogeneous densities, with hyperdense peripheral areas, as multiple nodular calcifications of less than 1 cm. In the central part of the mass, a big hypodense area was observed. There was no evidence of extrahepatic disease. Grossly, the tumor was well circumscribed with multiple nodular calcifications. The tumor was characterized by the presence of cohesive nests of bland spindle cells arranged in short fascicles and surrounded by desmoplastic stroma, intermixed with epithelioid cells. Mitotic activity was very low. Extensive osteoid formation was seen inside the cell nests. The tumor cells showed cytoplasmic reactivity for vimentin and pan-cytokeratin. The cells of desmoplastic stroma were immunoreactive for actin. The biologic behavior is still uncertain with only 5 published cases, but current information suggests that they are low-grade tumors with an indolent course. The clinical and morphologic features of this tumor are very similar to those of tumors previously reported as “nested stromal-epithelial tumor of liver” and “ossifying stromal-epithelial tumor of liver.” We describe the histologic, immunohistochemical, and molecular genetic features of a case of desmoplastic spindle cell tumor of the liver and review the literature.Desmoplastic nested spindle cell tumor of the liver in an adultMaría Isabel Oviedo Ramírez, Agueda Bas Bernal, Eduardo Ortiz Ruiz, Juan Bermejo, Enrique De Alava, Teresa Hernández10.1016/j.anndiagpath.2009.03.009Annals of Diagnostic Pathology 14, 1 (2010)2009-11-02Annals of Diagnostic Pathology2009-11-02141S1092-9134(09)X0007-9Case Reports4449http://www.annalspathology.com/article/PIIS1092913409000392/abstract?rss=yesAbstract: Desmoplastic fibroma (DF) is a rare neoplasm of bone, showing infiltrative and locally aggressive nature. Here, we report a case of DF with an unusual histology arising in a 41-year-old female in the left distal femur, which was detected by plain x-ray as an osteolytic lesion and by magnetic resonance imaging as a well-demarcated mass with endosteal scalloping. Pathologically, the tumor was composed mainly of bland-looking spindle cells in abundant collagenous stroma, accompanied with areas of myxofibrosarcomatous and malignant fibrous histiocytomatous components. These histologically different areas were admixed with each other. The array-based comparative genomic hybridization study on the histologically different areas showed some specific gained or lost loci according to their histologic features. The specific genetic events and the histologic features of this case might represent the malignant transformation of DF.Desmoplastic fibroma with malignant transformationHye Sook Min, Hyun Gyui Kang, Joo-Hyuk Lee, Geon Kook Lee, Jae Y. Ro10.1016/j.anndiagpath.2009.04.004Annals of Diagnostic Pathology 14, 1 (2010)2009-06-22Annals of Diagnostic Pathology2009-06-22141S1092-9134(09)X0007-9Case Reports5055http://www.annalspathology.com/article/PIIS1092913409000586/abstract?rss=yesAbstract: A 39-year-old woman presented with an incidentally discovered mass of the left adrenal fossa. Computed tomography and magnetic resonance imaging did not show any other lesion. Histologically, this mass was composed of a dense proliferation of spindle cells with a fibrosarcomatous-like pattern. Immunohistochemistry using anticytokeratin showed some epithelial cells within the tumor. The diagnosis of primitive synovial sarcoma of the left adrenal fossa was confirmed by the presence of the characteristic t(X;18) translocation. Despite radiotherapy, several chemotherapies, and 2 other surgical resections, the patient died 30 months after the initial diagnosis. To our knowledge, this report constitutes the first described case of synovial sarcoma arising in the adrenal gland.Unexpected diagnosis for an adrenal tumor: synovial sarcomaPierre-Alexandre Just, Frédérique Tissier, Stéphane Silvera, Bertrand Dousset, Stelly Ballet, Olivier Delattre, Marie-Cécile Vacher-Lavenu, François Goldwasser, Xavier Bertagna, Gonzague De Pinieux10.1016/j.anndiagpath.2009.05.004Annals of Diagnostic Pathology 14, 1 (2010)2009-08-10Annals of Diagnostic Pathology2009-08-10141S1092-9134(09)X0007-9Case Reports5659http://www.annalspathology.com/article/PIIS1092913409000860/abstract?rss=yesAbstract: Sclerosing hemangioma of the lung is a rare neoplasm with polymorphic histologic features. Despite various patterns, there are 2 unifying cellular components: “surface cells” and “round cells.” Although histogenesis has been debated for decades, most ultrastructural, immunocytochemical, and molecular studies strongly indicate a neoplastic epithelial derivation for both cellular components. Herein, we present a review of sclerosing hemangioma and summarize the essential data regarding histologic, cytologic, and ancillary findings of this distinctive pulmonary neoplasm.So-called sclerosing hemangioma of lung: current conceptNeda Kalhor, Gregg A. Staerkel, Cesar A. Moran10.1016/j.anndiagpath.2009.07.002Annals of Diagnostic Pathology 14, 1 (2010)2009-12-11Annals of Diagnostic Pathology2009-12-11141S1092-9134(09)X0007-9Review Article6067http://www.annalspathology.com/article/PIIS1092913409001592/abstract?rss=yesInstructions to Authors10.1016/S1092-9134(09)00159-2Annals of Diagnostic Pathology 14, 1 (2010)2010-02-01Annals of Diagnostic Pathology2010-02-01141S1092-9134(09)X0007-9Review Article6868http://www.annalspathology.com/article/PIIS1092913409001580/abstract?rss=yesTable of Contents10.1016/S1092-9134(09)00158-0Annals of Diagnostic Pathology 14, 1 (2010)2010-02-01Annals of Diagnostic Pathology2010-02-01141S1092-9134(09)X0007-9FrontmatterA1A2http://www.annalspathology.com/article/PIIS1092913409001567/abstract?rss=yesMasthead10.1016/S1092-9134(09)00156-7Annals of Diagnostic Pathology 14, 1 (2010)2010-02-01Annals of Diagnostic Pathology2010-02-01141S1092-9134(09)X0007-9FrontmatterA3A3