Adenocarcinoma of anogenital mammary gland type arising from encapsulated papillary carcinoma: A rare vulvar tumor mimicking breast carcinoma.

Anogenital mammary-like glands are normal structures of the anogenital region. Tumors originating from these glands often exhibit a striking resemblance to their mammary gland counterparts. Herein, we present a rare case of adenocarcinoma of mammary gland type in the vulva of a 69-year-old female. Histopathologic examination revealed a complex lesion, which included a large encapsulated papillary carcinoma (EPC) with associated invasive carcinoma of mammary gland type and ductal carcinoma in situ (DCIS). The invasive component consisted mostly of invasive ductal carcinoma of no special type, with a notable focus of invasive mucinous carcinoma. p40 immunostain demonstrated a lack of myoepithelial cells in both the EPC and invasive carcinoma, but such cells expressed p40 around the ducts involved by DCIS. The main component of this lesion, EPC, was characterized by a papillary proliferation within a cystic space surrounded by a fibrous capsule without a myoepithelial layer. The histopathologic features of anogenital EPC closely resemble cutaneous hidradenoma papilliferum. Indeed, there have been a few reports in the literature describing cases where in situ and invasive carcinoma arose from a preexisting hidradenoma papilliferum. As tumors of anogenital mammary-like glands bear a closer resemblance to breast lesions than to skin tumors, we recommend that they be aligned with the classification of well-established breast lesions rather than cutaneous adnexal tumors.

Myxoinflammatory Fibroblastic Sarcoma.

MIFS is a low-grade fibroblastic sarcoma that predilects to superficial distal extremity soft tissue. It is composed of plump spindled and epithelioid cells, inflammatory infiltrates, and mucin deposits in a fibrosclerotic stroma. Large epithelioid cells harboring bizarre nuclei and virocyte-like macronucleoli and pleomorphic pseudolipoblasts are characteristic. While conventional MIFS has locally recurrent potential but minimal metastatic risk, tumors with high-grade histologic features have a greater risk for recurrence and metastasis. Wide local excision is the recommended treatment.

Clear cell chondrosarcoma: a review of clinicopathologic characteristics, differential diagnoses, and patient management.

Clear cell chondrosarcoma (CCC), an extremely rare primary bone tumor, is currently classified by the World Health Organization as a low-grade malignant cartilaginous neoplasm. Clinically, CCC occurs primarily in males with a peak incidence in the third to fifth decades of life, and occasionally, it presents in skeletally immature patients. Unlike conventional chondrosarcoma, CCC has a predilection for the epiphysis of long bones and often displays radiologic features reminiscent of chondroblastoma. The recommended treatment is wide operative resection. CCC has a local recurrence rate of approximately 30%, and nearly 20% cases metastasize mainly to bone and lung often a decade after surgical intervention. Incomplete excision or curettage is associated with a high rate of recurrence. Histologically, the process is characterized by infiltrative lobules and sheets of round to oval cells with abundant cleared cytoplasm and well-defined cell borders associated with trabecula of osteoid and woven bone, scattered osteoclasts, and foci of conventional low-grade chondrosarcoma in about one-half of cases. Correlation with clinical and radiologic characteristics, such as epiphyseal location and young patient age, assists in establishing a correct diagnosis. Pathologic diagnosis of CCC is complicated by the low diagnostic accuracy of core needle biopsy, overlapping histologic features with other matrix-rich primary bone tumors, and a lack of a specific immunohistochemical and molecular profile. DNA methylation-based profiling classifier (sarcoma classifier) is one recent technologic advancement that may help to confirm the histopathological diagnosis of CCC or indicate the need for thorough reassessment in cases where results contradict previous conventional findings.

Pulmonary artery angiomatoid fibrous histiocytoma mimicking pulmonary embolism.

A young man presented to the emergency department with pleuritic chest pain and shortness of breath. Of note, he recently went on a long-distance flight of about 9 hours. Given his recent long-distance travel and clinical symptoms, a pulmonary embolism was suspected. However, pathological examination of the excised pulmonary artery intraluminal mass demonstrated an angiomatoid fibrous histiocytoma. This case describes the clinicopathological and immunohistochemical features and molecular profile of a rare type of pulmonary artery tumour, a pulmonary artery angiomatoid fibrous histiocytoma.

Cellular angiofibroma arising in the anorectal region: clinicopathologic and immunohistochemical analysis of five cases.

Cellular angiofibroma (CA) is a rare, benign mesenchymal tumor with a predilection to the distal female and male genital tract. Extragenital examples of CA, including anorectal CAs, are exceedingly rare and documented mainly as single case reports. Herein, we analyze the clinicopathological and immunohistochemical features of 5 anorectal CAs. There were 4 males and one female ranging in age from 45 to 70 (median, 58) years at the time of surgery. Tumors arose in the superficial tissues of the anorectal (n = 3) and perianal (n = 2) regions. The tumors were well circumscribed ranging from 2 to 6.7 (median, 5.4) cm. All demonstrated a low to moderately cellular proliferation of cytologically bland spindled cells within a variably dense collagenous and focally myxocollagenous stroma and small- to medium-sized vessels featuring perivascular collagen deposition. Two cases showed degenerative and/or inflammatory changes. All 5 tumors strongly expressed CD34 and androgen receptor proteins, more variably expressed estrogen (n = 5) and progesterone (n = 4) receptor proteins and desmin (n = 3), and focally expressed alpha-smooth muscle actin (n = 3), GATA-3 (n = 2), and p16 (n = 1). Retinoblastoma protein expression was reduced (n = 4) (compared with expression in endothelial cells) or completely lost (n = 1). All patients were treated with simple surgical excision, and the 2 study members with follow-up data showed no evidence of local recurrence over a postoperative follow-up interval of 23 and 73 months. In comparison with conventional genital tract CA, our 5 anorectal CAs occurred mostly in males, were generally less cellular, and appear to follow a similar uneventful clinical course.

Total knee arthroplasty in hemophilia A.

Hemophilia A is a rare genetic disorder involving a deficiency of clotting factor VIII. Coagulation factor replacement therapy has prolonged the life expectancy of patients with hemophilia, but recurrent hemarthrosis of major joints is often a common occurrence. Therefore, orthopaedic adult reconstructive surgeons increasingly encounter hemophilic arthropathy in young adults and consider treating with total joint arthroplasty. In this report, the authors describe a patient with hemophilia A and severe knee osteoarthritis, who was subsequently treated with primary total knee arthroplasty. This rare case is an opportunity to explore a variety of unique clinical scenarios specific to patients with hemophilia, including the maintenance of optimal factor VIII levels through clotting factor infusions and prevention of a venous thromboembolic event.

Expression of MDM2 and p16 in angiomyolipoma.

Angiomyolipoma (AML) arises primarily from the kidney but may grow into the retroperitoneal space mimicking a primary retroperitoneal tumor. Fine needle aspiration (FNA) and core needle biopsy of AML, particularly the fat-predominant variant, may be difficult to distinguish from retroperitoneal well-differentiated liposarcoma (WDLS) or lipoma. Commonly used immunomarkers, MDM2 and p16, have proven useful in diagnosing WDLS and dedifferentiated liposarcoma (DDLS), while HMB45 and Melan-A are melanocyte-related markers characteristically expressed in AML. In this study, we investigated the utility of MDM2 and p16 along with HMB45 and Melan-A immunohistochemical analysis in distinguishing AML from WDL/DDLS or lipoma. Immunohistochemically, AMLs demonstrated focal MDM2 expression (40% of cases) and focal/diffuse expression of p16 (60%). AMLs marked focally or diffusely with HMB45 (76% of cases) and Melan-A (96%). These latter two immunomarkers were not expressed in any of the WDLS/DDLSs or lipomas tested. WDLS/DDLSs showed focal/diffuse expression of MDM2 (91% of cases) and p16 (97%). While focal expression of MDM2 and p16 was observed in 14% and 67% of lipomas, respectively, no lipoma exhibited diffuse MDM2 positivity. In our hands, MDM2 expression by itself cannot exclude the diagnosis of AML or lipoma, and p16 alone is not helpful in separating AML and conventional lipoma from WDLS/DDLS. However, along with morphology, an immunohistochemical battery including HMB45, Melan-A, MDM2 and p16 are useful in distinguishing AML from WDLS/DDLS or lipoma. For equivocal cases, fluorescence in situ hybridization for MDM2 should be performed.

Isolated Multinodular Soft-Tissue Rosai-Dorfman Disease on FDG PET/CT.

Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) is a rare systemic histiocytic disorder of unknown etiology characterized by the accumulation of enlarged non-Langerhans histiocytes within lymph nodes and extranodal sites. The histiocytes display characteristic emperipolesis (nondestructive engulfment of inflammatory cells) and are CD68 and S100 positive and CD1a negative. Although extranodal disease frequently occurs with nodal involvement, isolated extranodal disease is uncommon. We report a case of isolated localized subcutaneous multinodular disease on FDG PET/CT. We also include a companion classic Rosai-Dorfman case with extensive nodal involvement and a characteristic benign clinical course with spontaneous improvement.

Federation Nationale des Centers de Lutte Contre le Cancer grading of soft tissue sarcomas on needle core biopsies using surrogate markers.

Needle core biopsy (NCB) of soft tissue sarcomas (STSs) presents problems for French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) histological grading because small sample size hinders determination of necrosis and mitotic activity. We graded 53 STSs on NCB using a modified FNCLCC grading system that substitutes Ki-67 immunoexpression for mitotic count and uses a radiological assessment of necrosis, and compared the results with those obtained by conventional FNCLCC grading of the corresponding untreated, surgically resected specimen. Forty-eight of the 53 tumors were classified as malignant on NCB (concordance = 91%). The modified FNCLCC grade correctly separated high-grade (grades II and III) from low-grade sarcomas in 70% of cases and predicted the traditional FNCLCC grade given to the resected specimen in 49% of cases. Ki-67 scores of 2 or 3 were observed in 5 tumors classified as low-grade neoplasms on NCB but upgraded to a high-grade dedifferentiated liposarcoma on resection. Underestimated NCB grades were commonly encountered with lipomatous tumors due to sampling error, whereas Ki-67 or radiologic necrosis scores higher than the corresponding histological scores were responsible for the vast majority of overestimated NCB grades. Our FNCLCC grading scheme replacing conventional mitosis counting and histologic assessment of necrosis with surrogate markers is useful in separating high- and low-grade STSs on NCB for STS treatment planning. High Ki-67 rate should raise suspicion of a higher-grade component, particularly with fatty tumors.

Plexiform fibromyxoma with cotyledon-like serosal growth: A case report of a rare gastric tumor and review of the literature.

Plexiform fibromyxoma is a rare, benign mesenchymal neoplasm that predilects the gastric antrum and has potential for misdiagnosis as a gastrointestinal stromal tumor (GIST). The histology of the tumor is characterized by interwoven fascicular growth of cytologically bland spindled cells within a variably myxoid stroma. The current study reports the clinicopathological and immunohistochemical findings of a plexiform fibromyxoma resected from a 28-year-old Vietnamese female. The patient presented with acute, severe abdominal pain and worsening anemia. The initial fine-needle aspiration and needle core biopsy of the gastric antral mass led to an initial diagnosis of GIST. The subsequent distal partial gastrectomy revealed a 5.5-cm transmural antral mass that ulcerated the overlying mucosa and grew as variably elongated, myxoedematous, polypoid (cotyledon-like) excrescences from the serosal surface. Microscopically, the tumor demonstrated plexiform and multinodular growth of cytologically bland spindled cells proliferating in an abundant myxocollagenous stroma with a prominent capillary network. Tumor cells immunohistochemically expressed smooth muscle actin and CD10, but did not express CD117, Discovered on GIST-1 or nuclear ß-catenin. Follow-up evaluation 23 months post surgery revealed no evidence of residual tumor. A review the cases of this rare entity reported in the English language literature is also provided.

Anaplastic thyroid carcinoma with rhabdoid features.

Anaplastic thyroid carcinoma (ATC) is a rare, highly aggressive neoplasm, characterized by complete or partial composition by undifferentiated cells. We report a case of ATC with rhabdoid features in a 68-year-old male, who presented with a rapidly enlarging neck mass. Fine-needle aspiration (FNA) of the thyroid mass showed discohesive, pleomorphic round to polygonal rhabdoid cells with one to multiple eccentric, large, rounded nuclei with a prominent nucleolus, moderate to abundant, globoid cytoplasm which oftentimes harbor a pale para-nuclear inclusion. The cytoplasm of some cells contained variously sized, eosinophilic granules. Rare cells contained neutrophils in their cytoplasm. Mitoses including atypical mitotic figures and necrosis were readily seen. Histologic examination of needle core biopsy (NCB) revealed individual dispersed and sheets of pleomorphic neoplastic cells with similar cytomorphologic features as described above. The tumor extensively infiltrated a myxocollagenous stroma containing lymphocytes and neutrophils, and demonstrated foci of necrosis. Tumor cells were immunoreactive for keratins AE1/AE3, CAM5.2, and CK19; PAX-8, and p63, but negative for S-100, HMB-45, calcitonin, TTF-1, thyroglobulin, CD56, HBME-1, glypican-3, PAX-5, myogenin, CD31, and INI-1. The differential diagnosis of this malignant rhabdoid tumor is discussed.

Intranodal palisaded myofibroblastoma: another mesenchymal neoplasm with CTNNB1 (ß-catenin gene) mutations: clinicopathologic, immunohistochemical, and molecular genetic study of 18 cases.

Intranodal palisaded myofibroblastoma is a benign, lymph node-based myofibroblastic tumor of unknown pathogenesis. We report the clinicopathologic, immunohistochemical, and molecular genetic features of this rare entity. The study cohort consisted of 14 men and 4 women ranging in age from 31 to 65 (mean, 47; median 49) years with tumors arising in inguinal lymph nodes (n=15), a neck lymph node (n=1), and undesignated lymph nodes (n=2). Most individuals presented with a painless mass or lump. Possible trauma/injury to the inguinal region was documented in 4 cases. Tumors ranged in size from 1.0 to 4.2 (mean, 3.1; median; 3.0) cm. Microscopically, the process presented as a well-circumscribed, oftentimes pseudoencapsulated nodule (n=17) or nodules (n=1). Tumors consisted of a cellular proliferation of cytologically bland, spindled cells arranged in short fascicles and whorls within a finely collagenous (n=11) or myxocollagenous (n=7) matrix. In 12 tumors, scattered fibromatosis-like fascicles of spindled cells were noted. Histologic features characteristic of the process included nuclear palisades (n=16 cases), collagenous bodies (n=15), and perinuclear intracytoplasmic hyaline globules (n=10). Mitotic activity ranged from 0 to 8 (mean, 2; median, 1) mitotic figures/50 high-powered fields with no atypical division figures identified. Immunohistochemically, all tumors tested expressed smooth muscle actin and/or muscle-specific actin (n=5, each), and nuclear ß-catenin and cyclin D1 (n=8, each). The latter 2 results prompted a screening for mutations in the ß-catenin gene glycogen synthase kinase-3 ß phosphorylation mutational "hotspot" region in exon 3 using polymerase chain reaction amplification and Sanger sequencing. Single nucleotide substitutions leading to missense mutations at the protein level were identified in 7 of 8 (88%) analyzed tumors and are responsible for the abnormal expression of ß-catenin and cyclin D1. These results demonstrate that mutational activation of the ß-catenin gene is likely a pivotal event in the pathogenesis of intranodal palisaded myofibroblastoma.

Examination of national lymph node evaluation practices for adult extremity soft tissue sarcoma.

BACKGROUND AND OBJECTIVES: Lymph node evaluation recommendations for extremity soft tissue sarcoma (ESTS) are absent from national guidelines. Our objectives were (1) to assess rates and predictors of nodal evaluation, and (2) to assess rates and predictors of nodal metastases. METHODS: ESTS patients from the National Cancer Data Base (2000-2009) were assessed, and regression models were used to identify factors associated with nodal evaluation and metastases. RESULTS: Of 27,536 ESTS patients, 1,924 (7%) underwent nodal evaluation, and of these, 290 (15%) had nodal metastases. Nodal evaluation was most frequently performed for rhabdomyosarcoma (15.6%), angiosarcoma (10.0%), clear cell sarcoma (39.3%), epithelioid sarcoma (28.1%), and synovial sarcoma (9.3%). On multivariable analysis, factors associated with nodal evaluation included histologic subtype, tumor size, and grade. Nodal metastasis rates were highest among patients with rhabdomyosarcoma (32.1%), angiosarcoma (24.1%), clear cell sarcoma (27.7%), and epithelioid sarcoma (31.8%). On multivariable analysis, factors associated with nodal metastases included histologic subtype, tumor size, and grade. CONCLUSIONS: Nodal evaluation rates are highest among certain expected subtypes but are generally low. However, nodal metastasis rates for many histologic subtypes in patients selected for lymph node evaluation may be higher than previously reported. Multi-institutional studies should address nodal evaluation for ESTS.

Myxoinflammatory fibroblastic sarcoma: a clinicopathologic analysis of 104 cases, with emphasis on predictors of outcome.

In this study, we examine the clinicopathologic features of 104 cases of myxoinflammatory fibroblastic sarcoma (MIFS), a low-grade, inflammatory fibromyxoid tumor with a predilection to distal extremity soft tissue, and attempt to identify factors predictive of aggressive behavior. The study cohort consisted of 49 male and 55 female patients ranging in age from 17 to 83 (mean, 42; median, 39) years. The tumor arose primarily on the dorsal aspect of the distal extremities as a solitary and usually painless mass. Tumors ranged in size from 0.5 to 15 (mean, 3.2; median; 2.4) cm. Microscopically, tumors consisted of variably cellular and inflamed fibromyxoid tissue growing as a lobulated mass or as multiple nodules within subcutaneous tissue or along tendinofascial planes. Tumor cells ranged from plump spindled to more epithelioid cells with enlarged, vesicular nuclei. Characteristic of the process was a strikingly bizarre cell with an inclusion body-like nucleolus (85% of cases) and/or a smudgy hyperchromatic nucleus (51%) present in all but 7 cases. The mitotic rate per 50 high-power field ranged from 0 to 13 (mean, 2,9; median, 2) mitoses. Twenty-two tumors demonstrated 1 or more of the following atypical features: (1) foci with complex sarcoma-like vasculature; (2) hypercellular areas; and (3) increased mitotic activity or atypical mitotic figures. Immunohistochemically, tumor cells demonstrated immunoreactivity for vimentin (100%), D2-40 (86%), CD34 (50%), keratin(s) (33%), CD68 (27%), actin(s) (26%), desmin (9%), S-100 protein (7%), and epithelial membrane antigen (6%). Thirty of 59 patients (51%) with follow-up data suffered (at least) 1 local recurrence, and 1 patient developed metastatic disease after multiple local recurrences. Completeness of initial surgical excision was the only clinicopathologic parameter that statistically correlated with a lower incidence of recurrence (P=0.004). Histologically atypical MIFS recurred more often than conventional tumors (67% vs. 47%), but the difference was not statistically significant (P=0.35). Our study shows that histologic features often associated with more aggressive sarcomas do not substantially impact the morbidity of MIFS, and complete surgical excision provides the best chance for disease-free survival.

Sarcomatoid (spindle cell) carcinoma of the pancreas: A case report and review of the literature.

Sarcomatoid (spindle cell) carcinoma of the pancreas is a rare, high-grade epithelial malignancy composed predominantly or exclusively of spindle cells demonstrating evidence of epithelial derivation, but no features indicative of a specific line of mesenchymal differentiation. The current study presents the case of an 85-year-old Caucasian male with a tumor mass in the body of the pancreas. The individual subsequently underwent a distal pancreatectomy, splenectomy and partial gastrectomy. Microscopic examination of the 3.3-cm mass located in the body of the pancreas revealed a small, but high-grade, adenocarcinomatous component that blended imperceptibly with malignant spindle cells. No light microscopic or immunohistochemical evidence of specific mesenchymal differentiation was identified, and the spindle cells, as in the case of the carcinoma, were diffusely keratin-positive. Sarcomatoid (spindle cell) carcinoma defined in this way rarely presents in the pancreas, with, to the best of our knowledge, only six cases reported in the English literature.

Assessment of multimodality therapy use for extremity sarcoma in the United States.

BACKGROUND: Extremity sarcoma national guidelines offer several stage-specific treatment options; therefore, treatment approaches are not standardized. Our objectives were to examine multimodality treatment trends, practice patterns, and factors associated with neoadjuvant or postoperative adjuvant therapy utilization. METHODS: Using the National Cancer Data Base (2000-2009), treatment of non-metastatic extremity sarcoma was examined. Regression models were developed to identify factors associated with neoadjuvant or postoperative adjuvant therapy receipt and treatment sequence. RESULTS: Twenty-two thousand fifty-one patients underwent resection (stage I: 45.2%, stage II: 27.7%, stage III: 27.1%). Over 10 years, neoadjuvant radiation (6.4-11.6%, P < 0.001) and chemotherapy utilization (1.4-1.8%, P = 0.037) increased, while postoperative radiation (34.3-29.2%, P = 0.023) and trimodality therapy decreased (10.5-9.6%, P = 0.002). After adjusting for age, comorbidities, and histology, patients with large high-grade tumors treated at high-volume academic centers were more likely to receive neoadjuvant therapy (all P < 0.001). Postoperative chemotherapy utilization was associated with younger age, synovial histology, high grade, and surgical margins (all P < 0.001). CONCLUSIONS: Utilization of neoadjuvant therapy for extremity sarcoma has increased over time. Practice patterns are not only related to tumor size, grade, histology, and margins but also hospital type. Opportunities remain to better define the most effective multimodality treatment for extremity sarcoma.

Superficial paramucosal clear cell sarcoma of the soft parts resembling melanoma in a 13-year-old boy.

Clear cell sarcoma (CCS) of tendons and aponeuroses, also known as melanoma of soft parts, represents an aggressive rare malignancy that is characterized by a nested or fascicular pattern of spindled cells and a pathognomonic reciprocal translocation, t(12;22)(q13;q12), that results in the fusion of EWSR1 and ATF1 genes. Numerous recent studies have recognized the importance of a cutaneous CCS variant that can mimic a broad spectrum of entities, including spindle cell melanoma, spindle cell squamous carcinoma, cutaneous leiomyosarcoma and atypical fibroxanthoma. We report a case of a 13-year-old boy with cutaneous CCS who presented with a few months history of an asymptomatic papule on the lower lip that was suggestive of a mucocele. Biopsy of the lesion showed a wedge shaped neoplasm arranged in nests and fascicles of epithelioid- to oval-shaped cells with pale cytoplasm, open chromatin and prominent nucleolus. The superficial component was closely opposed to the basal epithelium resembling the junctional nests of a melanocytic neoplasm. The process extended into and involved the striated muscle of the lip. The cells expressed S-100, CD99 and synaptophysin by immunohistochemistry, and there was focal HMB-45 and microphthalmia transcription factor (MiTF) positivity as well. Fluorescence in situ hybridization confirmed the presence of the t(12;22) (ESWR1-ATF1) translocation.

Inguinal smooth muscle tumors in women-a dichotomous group consisting of Müllerian-type leiomyomas and soft tissue leiomyosarcomas: an analysis of 55 cases.

Assessment of the biological potential of smooth muscle tumors can be difficult and depends primarily on tumor site, stage, and histologic parameters. In this study, we examined the clinicopathologic and immunohistochemical features of 55 noncutaneous inguinal smooth muscle tumors of women (age range, 20 to 82 y; median, 57 y). Histologically, 23 tumors were considered as leiomyomas. They showed low mitotic activity (range, 0 to 6 mitoses/10 high-power fields, without atypical mitotic figures), minimal cytologic atypia, and absence of coagulative necrosis. Fifteen of these tumors histologically resembled conventional uterine leiomyomas and 8 resembled their variants: lipoleiomyomas (n = 2) and epithelioid variants (n = 6). The mean size was 7.8 cm, and half of the tumors with specified location arose in association with the round ligament. Immunohistochemical expression of estrogen receptor (ER) and/or Wilms tumor protein (WT1) was detected in most cases (83%), supporting Müllerian derivation. Follow-up data (range, 10 to 29 y; median, 13 y) on 11 patients showed that all were alive without disease or death from unrelated causes. The second group, classified as leiomyosarcomas, consisted of 32 mitotically active smooth muscle tumors, almost invariably with atypical mitotic figures, and exhibiting significant cytologic atypia. These patients were older than those with leiomyomas, and their tumors were mostly subcutaneous with a mean tumor size of 5.4 cm. Two leiomyosarcomas showed a femoral vein origin, but none were associated with the round ligament. All but 3 leiomyosarcomas were negative for ER. Follow-up data on 13 patients (range, 2 mo to 30 y; median, 4.5 y) showed that 5 died of metastatic sarcoma. Six individuals were alive without disease (median, 16 y), and 2 died of unrelated causes. In conclusion, inguinal smooth muscle tumors in women are a dichotomous group. They consist of ER/WT1-positive Müllerian-type leiomyomas resembling uterine leiomyomas with an excellent prognosis and conventional LMSs that are usually ER/WT1-negative and show a variable malignant course. Separation of these 2 categories is important for prognostication and optimal patient management, and is aided by immunohistochemical studies for ER and WT1.

Targeting prostate cancer angiogenesis through metastasis-associated protein 1 (MTA1).

BACKGROUND: Metastasis-associated protein 1 (MTA1) is overexpressed in many forms of cancer types but its role in prostate cancer (PCa) progression and metastasis has not been explored. In this study, we addressed the functional and biological role of MTA1 in PCa. METHODS: Gene expression profiling was used to determine MTA1 overexpression during PCa cell-bone interaction. Immunohistochemistry was used to detect MTA1 on tissue microarrays (TMA) and vascular endothelial growth factor (VEGF), CD31, and Ki67 in xenografts. We used retroviral or lentiviral RNAi transduction of PCa cells to establish MTA1 knockdowns. RT-PCR, Western blot, invasion, and endothelial cell migration assays were used to characterize the cells in vitro. The role of MTA1 in PCa tumorigenesis was evaluated in mouse xenografts. RESULTS: We identified MTA1 as a component of bone metastasis signature in PCa, which suggested a possible role for MTA1 in PCa progression and metastasis. MTA1 was expressed at higher levels in PCa cell lines than in normal prostate epithelial cells. Silencing MTA1 significantly suppressed the invasion and angiogenic activity of the cells in vitro and delayed tumor formation and development in mouse xenografts. Tumors that express MTA1 had higher proliferative indices, secreted higher levels of VEGF and were more vascularized. Analysis of the human TMA showed positive correlation between MTA1 nuclear localization/staining intensity and PCa aggressiveness. CONCLUSIONS: MTA1 pro-angiogenic and pro-invasive functions create permissive environment for PCa tumor growth and likely support metastasis. Taken together with its predictive values, MTA1 can be utilized both as a prognostic marker and a therapy target in PCa.

Leiomyosarcoma of the inferior vena cava: clinicopathologic study of 40 cases.

This report details the clinicopathologic features and follow-up data on 40 cases of inferior vena cava leiomyosarcoma, a rare sarcoma with a poor prognosis. Study cohort consisted of 31 females and 9 males (mean age, 53 y), whose material was accessioned to the Armed Forces Institute of Pathology between 1976 and 2008. Inferior vena cava leiomyosarcomas ranged in size from 3.5 to 15.0 (median, 8.5) cms, and most involved the middle segment of the vessel and grew extraluminally. Eleven leiomyosarcomas were French Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) histologic grade I; 21, grade II; and 5 were grade III. Eleven of 33 patients managed by complete or radical resection had involved surgical margins. Twenty of the 34 patients (59%) with clinical follow-up data (mean, 33.5; median, 51 mo) died of sarcoma-related complications and 9 (26%) of unknown causes. The 5-year and 10-year survival rates after resection without documented residual macroscopic disease were 50% and 22%, respectively. Two patients are alive without disease 9 and 18 years after last surgical intervention. Suprahepatic vena caval and right atrial involvement by tumor, predominant intraluminal tumor growth, and residual postsurgical macroscopic disease were factors that statistically correlate with death within 2 years. By univariate analysis, intraluminal tumor (P=0.03), liver injury or failure (compromised liver) (P=0.01), and moderate to poor tumor differentiation (P=0.03) were associated with increased tumor-related mortality, whereas a compromised liver (P=0.01) was the only factor correlated with mortality by multivariate analysis. Our study concludes that a macroscopic resection of localized inferior vena cava leiomyosarcoma provides the best chance for long-term survival, suprahepatic tumors often result in early death, and a compromised liver correlates with overall poor survival, but French Federation Nationale des Centres de Lutte Contre le Cancer grading does not affect prognosis.