Mammary-like Carcinoma of the vulva: A diagnostic challenge.

Mammary-like carcinoma of the vulva is incredibly rare with less than 30 cases published since 1935, and the similarities of such pathology between breast cancer metastases, squamous adenocarcinoma, Bartholin gland carcinomas, etc, make an accurate diagnosis challenging. A diagnosis can be made utilizing immunohistochemical staining and patient history to rule out more likely causes such as metastases to ensure a correct diagnosis.

Plasmacytoid Urothelial Carcinoma of the Urinary Bladder: A Clinicopathologic and Immunohistochemical Analysis of 49 Cases.

OBJECTIVES: Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare histologic variant. We retrospectively analyzed a large series of bladder PUC from a single institution. METHODS: The patients consisted of 44 men and five women with a mean age of 62 years (range, 45-86 years). RESULTS: PUC was pure in 23 cases and mixed with other histologic types in 26 cases. All PUCs diffusely invaded the bladder wall. Most PUCs lacked immunoreactivity for the retinoblastoma (RB) gene protein (12/32) and E-cadherin (8/30). Of the 44 patients with follow-up information, 25 died of PUC at a mean of 23 months, whereas 19 patients were alive at a mean of 22 months. CONCLUSIONS: Our findings support that bladder PUC is a highly aggressive disease. The lack of E-cadherin expression in PUCs may underlie the distinct discohesive histologic appearance, and abnormal function of the RB gene may be implicated in the development of PUC.

Analysis and significance of c-MET expression in adenoid cystic carcinoma of the salivary gland.

Adenoid cystic carcinoma (ACC), a rare salivary gland malignancy, is a histogenetic, morphologic, and clinical heterogeneous disease. Extensive efforts have been made to characterize molecular events associated with these tumors, including the identification of prognostic and predictive biomarkers. Increased copy number gain and amplification of c-Met, the cell surface receptor for hepatocyte growth factor, has been shown to enhance tumor growth and invasiveness and promote metastasis in certain tumor types. In this study, we evaluated the expression of c-Met by immunohistochemistry (IHC) in a large cohort of salivary gland ACCs and examined its clinicopathologic implications. Archival formalin-fixed paraffin-embedded blocks from 200 ACC patients were used in this study. Pathologic patterns and phenotypic expression of c-Met were recorded and compared with clinical factors including gender, age, disease stage at diagnosis, and clinical outcomes. Correlations between c-MET expression and clinical characteristics were assessed by Pearson's chi-square test or by the 2-tailed Fisher exact test. Curves describing overall survival were generated by Kaplan-Meier product limit method. Strong c-MET expression was seen in inner ductal and outer myoepithelial cells in 53.2% of the cases. There was no correlation between c-Met overexpression and clinicopathologic parameters or patient's overall survival ( p = .94074). In conclusion, c-MET expression is high in a significant subgroup of ACC patients. While c-MET expression is not a prognostic factor in ACC, its role as a predictive marker of benefit from MET inhibitors deserves further investigation.

Cutaneous meningioma: a potential diagnostic pitfall in p63 positive cutaneous neoplasms.

Cutaneous meningiomas are divided into three groups. Type I lesions present at birth and are derived from ectopic arachnoid cells. Type II lesions usually present in adults and are derived from arachnoid cells surrounding nerve bundles. Type III lesions are due to direct extension or metastasis from dural-based neoplasms. Dural-based meningiomas are known to express p63. The aim of our study is to examine the expression of p63 in type II and type III meningioma. Two cases of cutaneous meningioma (type II and type III) were evaluated for the expression of p63, EMA, CK 5/6, S100 and CD31. The cells of interest were spindled to epithelioid and arranged in a whorling pattern. Immunohistochemical staining showed expression of EMA and p63 in both cases, while stains for CK 5/6, S100 and CD31 were negative. Among cutaneous tumors, p63 is considered a marker of epithelial derivation, as it is positive in epidermal and adnexal neoplasms. It is important to be aware of p63 expression in the context of cutaneous meningioma to avoid misinterpretation as an epithelial tumor. On the basis of our small study, it is unlikely that p63 expression would be helpful in distinguishing between type II and type III meningioma, as both may be p63-positive.

Expression of MiTF may be helpful in differentiating cellular neurothekeoma from plexiform fibrohistiocytic tumor (histiocytoid predominant) in a partial biopsy specimen.

BACKGROUND: Overlapping histopathologic features of cellular neurothekeoma (CNT) and plexiform fibrohistiocytic tumor (PFHT), when both are predominantly composed of histiocytoid cells, make distinction between these entities challenging. Some have suggested that CNT and PFHT are related entities. No prior study has demonstrated a reliable immunohistochemical panel to differentiate these entities. METHODS: Skin biopsies diagnosed as CNT and PFHT, from 2004 to 2010 were retrieved with accompanying pathology reports. Each case was reviewed by at least 2 dermatopathologists and 2 soft tissue pathologists for confirmation of diagnosis. All cases were then evaluated for immunohistochemical expression of PAX2, NKIC3, CD10, and microphthalmia transcription factor (MiTF). RESULTS: Histopathologically, the histiocytoid areas of each tumor shared similar architecture, demonstrating nests and fascicles of histiocytoid to spindled cells, with some separation of nests by collagen bands. Both CNT and PFHT were uniformly positive for NKIC3 and CD10, and both were frequently PAX2 positive. MiTF was strongly and diffusely positive in CNT and was consistently negative in the PFHT. CONCLUSIONS: CNT and PFHT share many histopathologic features and immunohistochemical staining patterns. Of the stains we evaluated, we found that expression of MiTF may be a reliable marker for distinguishing CNT from histiocytoid-predominant PFHT, especially in instances where only a small part of the tumor is sampled for evaluation.

Extra-acral cutaneous/soft tissue sclerosing perineurioma: an under-recognized entity in the differential of CD34-positive cutaneous neoplasms.

BACKGROUND: Perineuriomas are an uncommon group of tumors composed of perineurial cells of peripheral nerve sheath lineage. Variants include soft tissue (extraneural), intraneural, sclerosing, reticular and plexiform forms. Sclerosing perineuriomas have been reported to occur almost exclusively on the hands of young men. Herein, we report three extra-acral cutaneous/soft tissue perineuriomas that show significant associated sclerosis. METHODS: Skin biopsy specimens from three patients were evaluated for cytomorphology and degree of associated sclerosis, which was classified as either focal or diffuse. Immunohistochemical expression of epithelial membrane antigen (EMA), CD34 and S-100 was also assessed to facilitate further classification. RESULTS: Histopathologically, the tumors showed both focal and diffuse sclerosis, and lesional cells were generally spindled in shape. Immunohistochemical staining showed diffuse positivity for CD34 and focal or diffuse positivity for EMA. The cells uniformly lacked expression of S-100 protein. CONCLUSIONS: Sclerosing perineuriomas can occur in extra-acral locations and should be considered in the differential of EMA-positive cutaneous spindle-cell proliferations. It is also important to recognize that perineuriomas can express CD34 and should be considered in the differential diagnosis of CD34-positive cutaneous neoplasms.

Contributions of muscles and passive dynamics to swing initiation over a range of walking speeds.

Stiff-knee gait is a common walking problem in cerebral palsy characterized by insufficient knee flexion during swing. To identify factors that may limit knee flexion in swing, it is necessary to understand how unimpaired subjects successfully coordinate muscles and passive dynamics (gravity and velocity-related forces) to accelerate the knee into flexion during double support, a critical phase just prior to swing that establishes the conditions for achieving sufficient knee flexion during swing. It is also necessary to understand how contributions to swing initiation change with walking speed, since patients with stiff-knee gait often walk slowly. We analyzed muscle-driven dynamic simulations of eight unimpaired subjects walking at four speeds to quantify the contributions of muscles, gravity, and velocity-related forces (i.e. Coriolis and centrifugal forces) to preswing knee flexion acceleration during double support at each speed. Analysis of the simulations revealed contributions from muscles and passive dynamics varied systematically with walking speed. Preswing knee flexion acceleration was achieved primarily by hip flexor muscles on the preswing leg with assistance from biceps femoris short head. Hip flexors on the preswing leg were primarily responsible for the increase in preswing knee flexion acceleration during double support with faster walking speed. The hip extensors and abductors on the contralateral leg and velocity-related forces opposed preswing knee flexion acceleration during double support.

Predicting outcomes of rectus femoris transfer surgery.

Rectus femoris transfer surgery is a common treatment for stiff knee gait in children with cerebral palsy. Unfortunately, the improvement in knee motion after surgery is inconsistent. There is great interest in understanding the causes of stiff knee gait and determining predictors of improved knee motion after surgery. This study demonstrates that it is possible to predict whether or not a patient's knee motion will improve following rectus femoris transfer surgery with greater than 80% accuracy. A predictive model was developed that requires only a few preoperative gait analysis measurements, already collected as a routine part of treatment planning. Our examination of 62 patients before and after rectus femoris transfer revealed that a combination of hip power, knee power, and knee flexion velocity at toe-off correctly predicted postoperative outcome for 80% of cases. With the addition of two more preoperative measurements, hip flexion and internal rotation, prediction accuracy increased to nearly 88%. Other combinations of preoperative gait analysis measurements also predicted outcomes with high accuracy. These results provide insight into factors related to positive outcomes and suggest that predictive models provide a valuable tool for determining indications for rectus femoris transfer.

Mechanisms of improved knee flexion after rectus femoris transfer surgery.

Rectus femoris transfer is frequently performed to treat stiff-knee gait in subjects with cerebral palsy. In this surgery, the distal tendon is released from the patella and re-attached to one of several sites, such as the sartorius or the iliotibial band. Surgical outcomes vary, and the mechanisms by which the surgery improves knee motion are unclear. The purpose of this study was to clarify the mechanism by which the transferred muscle improves knee flexion by examining three types of transfers. Muscle-actuated dynamic simulations were created of ten children diagnosed with cerebral palsy and stiff-knee gait. These simulations were altered to represent surgical transfers of the rectus femoris to the sartorius and the iliotibial band. Rectus femoris transfers in which the muscle remained attached to the underlying vasti through scar tissue were also simulated by reducing but not eliminating the muscle's knee extension moment. Simulated transfer to the sartorius, which converted the rectus femoris' knee extension moment to a flexion moment, produced 32+/-8 degrees improvement in peak knee flexion on average. Simulated transfer to the iliotibial band, which completely eliminated the muscle's knee extension moment, predicted only slightly less improvement in peak knee flexion (28+/-8 degrees ). Scarred transfer simulations, which reduced the muscle's knee extension moment, predicted significantly less (p<0.001) improvement in peak knee flexion (14+/-5 degrees ). Simulations revealed that improved knee flexion following rectus femoris transfer is achieved primarily by reduction of the muscle's knee extension moment. Reduction of scarring of the rectus femoris to underlying muscles has the potential to enhance knee flexion.

Importance of preswing rectus femoris activity in stiff-knee gait.

Stiff-knee gait is characterized by diminished and delayed knee flexion during swing. Rectus femoris transfer surgery, a common treatment for stiff-knee gait, is often recommended when a patient exhibits prolonged activity of the rectus femoris muscle during swing. Treatment outcomes are inconsistent, in part, due to limited understanding of the biomechanical factors contributing to stiff-knee gait. This study used a combination of gait analysis and dynamic simulation to examine how activity of the rectus femoris during swing, and prior to swing, contribute to knee flexion. A group of muscle-actuated dynamic simulations was created that accurately reproduced the gait dynamics of ten subjects with stiff-knee gait. These simulations were used to examine the effects of rectus femoris activity on knee motion by eliminating rectus femoris activity during preswing and separately during early swing. The increase in peak knee flexion by eliminating rectus femoris activity during preswing (7.5+/-3.1 degrees ) was significantly greater on average (paired t-test, p=0.035) than during early swing (4.7+/-3.6 degrees ). These results suggest that preswing rectus femoris activity is at least as influential as early swing activity in limiting the knee flexion of persons with stiff-knee gait. In evaluating rectus femoris activity for treatment of stiff-knee gait, preswing as well as early swing activity should be examined.