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.

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.

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.

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.

Genomic Landscape of Osteosarcoma of Bone in an Older-Aged Patient Population and Analysis of Possible Etiologies Based on Molecular Signature.

Background: Osteosarcoma (OS), the most common primary malignant bone tumor, occurs mostly in the pediatric and adolescent (P/A) population where it has been subject to intense study whereas OS arising in the older-aged adult population has undergone less scrutiny. Materials and Methods: In this study, we assess the molecular aberrations detected in eight older adult patients (>59 years of age) with OS of bone by whole-exome sequencing (WES) on formalin-fixed, paraffin-embedded tissue and quantified the contributions of endogenous and exogenous mutational processes to tumor mutational burden and to tumorigenesis through computational analysis. Results: We identified 86 clinically significant somatic mutations. TP53 mutations occurred in OSs of three patients and one patient harbored a pathogenic germline mutation of TP53. Loss-of-heterozygosity of DNA-damage repair genes occurred in all six tumors evaluated. Computational analysis of single nucleotide variants within each tumor detected eight distinct mutagenic processes of which age-associated mutational processes, thiopurine chemotherapy, and defective homologous DNA recombination repair contributed the most to both tumor mutation burden and tumor pathogenesis. Conclusion: The genomic landscape of our older OS patients deciphered by WES is extremely diverse with only 15% of mutated somatic genes uncovered in our study previously described in P/A-enriched OS studies. Endogenous age-related mutagenic processes, defective DNA homologous recombination repair, and exogenous effects of chemotherapy are mainly responsible for pathogenic mutations in OS occurring in our cohort.

Use of Mitotic Activity and the Size of Any Dedifferentiated Component for Risk Assessment in MDM2-Amplified Liposarcoma.

CONTEXT.­: The characteristic molecular signature for both atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma is amplified sequences derived from chromosome 12q13-15, including MDM2 proto-oncogene (MDM2). As the progression of atypical lipomatous tumor/well-differentiated liposarcoma to the more aggressive dedifferentiated liposarcoma has the potential to adversely affect patient outcomes, the extent of the latter component might be important to evaluate. OBJECTIVE.­: To investigate the correlation between clinicopathologic characteristics, including tumor size, modified Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, molecular data, and outcomes in 123 surgically resected MDM2-amplified liposarcomas. DESIGN.­: Pathology reports and clinical records were reviewed. A log-rank test was used to compare the survival trends, and univariate logistic regression was performed to identify variables associated with adverse events (distant metastasis and/or death), from which the P value was derived to construct a multivariate regression model. RESULTS.­: In univariate analysis, the largest single dimension of the dedifferentiated component, the percentage of cells with gain of chromosome 12, mitotic count, and the presence of modified FNCLLC grade 3 were associated with adverse events. In multivariate analysis, the largest single dimension of the dedifferentiated component (odds ratio: 1.169; 95% CI: 1.053, 1.299; P = .003), and a higher mitotic count (odds ratio: 1.133; 95% CI: 1.037, 1.237; P = .006) were correlated with adverse events. There was no statistically significant association between current local recurrence status, overall largest tumor dimension, overall tumor volume, MDM2 copy number, or MDM2 to chromosome 12 centromere probe ratio and adverse outcomes. CONCLUSIONS.­: Staging dedifferentiated liposarcoma based on the size of the dedifferentiated component better predicts the outcome.

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.

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.

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.

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.

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.

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.

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.

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.

Calcareous lesions of the distal extremities resembling tumoral calcinosis (tumoral calcinosislike lesions): clinicopathologic study of 43 cases emphasizing a pathogenesis-based approach to classification.

Herein, we analyze the clinicopathologic features of 46 distal extremity lesions that have histologic features similar to conventional tumoral calcinosis (tumoral calcinosislike; TC-L). The study included 31 females and 12 males (whites:non-whites>3:1) ranging in age from 1 to 91 (mean, 39; median, 42) years. The lesions presented in fingers (n=20), feet (n=10), wrist (n=6), hands (5), toes (n=4), and ankle (n=1) were solitary in all but 5 patients and ranged in size from 0.3 to 4.5 (mean, 1.6; median, 1.4) cm. Chief initial complaints included presence of a painful (n=16) or asymptomatic (n=7) mass, and limitation of joint mobility (n=3). Pertinent clinical associations included antecedent trauma (n=7), scleroderma (n=3), long-standing osteoarthritis (n=3), bony deformities (n=5), including 2 infants with congenital hand malformations, and chronic renal failure (n=2). Patients were stratified into one of the 3 recognized clinical settings of TC: primary normophosphatemic (n=17), secondary (n=5), or primary hyperphosphatemic TC (n=1). The 20 remaining patients were placed in an "indeterminate TC" category. Most lesions were located in tenosynovial/fascial tissue, but 13 lesions involved dermis and 1 was intra-articular. Histologically, the process consisted of multiple cystic or cleftlike spaces bordered by histiocytes, osteoclastlike giant cells, and a variable inflammatory infiltrate and containing fibrin, granular calcific debris, and calcospherites. Pools of calcific debris bordered by sclerotic collagen and a sparse cellular element predominated in 4 cases. Cartilaginous metaplasia was identified in 10 lesions and evidence of hemorrhage or specific injury was observed in 12 examples. Follow-up data for 22 patients (interval range, 1 to 30 y; median, 6 y) revealed 17 individuals with no evidence of recurrent disease or the development of additional lesions after simple (local) excision. One patient (indeterminate TC) required reexcision of a thumb mass 1 year after surgery. All 3 scleroderma patients developed additional TC-L lesions. Acral TC-L lesions are histologically similar to conventional TC, but present as smaller size lesions. Most TC-L lesions are closely aligned with primary normophosphatemic or secondary TC. Acral TC-L lesions may be the first manifestation of scleroderma, where the process has the potential to follow an unrelenting course.

Neurothekeoma: an analysis of 178 tumors with detailed immunohistochemical data and long-term patient follow-up information.

This report describes the clinicopathologic findings in 176 patients who presented with 178 tumors currently referred to as neurothekeomas. Our study group included 64 males and 112 females, ranging from 20 months to 85 years old at the time of their first surgical procedure (median age: 17 y). Twenty-four percent of patients were or=30 years of age at initial diagnosis. The patients typically presented with a solitary, superficial, slow-growing, and relatively asymptomatic mass in the 0.3 to 2.0 cm size range. One patient had multiple tumors. More than 75% of the lesions involved the head (n=63), upper extremities (n=44), and shoulder girdle (n=27) regions. The tumors were evident a few weeks to 4 years (median duration: approximately 7 mo) before surgical resection was sought. Histologically, the lesions involved the dermis and/or subcutis, and they formed multinodular masses with varying amounts of myxoid matrix and peripheral fibrosis. On the basis of the amount of myxoid matrix, the tumors were subclassified as cellular (n=63), mixed (n=67), or myxoid (n=48). All cases had spindled and epithelioid mononuclear neoplastic cells with relatively abundant cytoplasm and indistinct cell borders. The majority of cases also had occasional multinucleated tumor cells. The lesional cells had a strong tendency for whorled growth, and oftentimes, focal fascicular growth was also present. Nuclear atypia was minimal in 62 cases, mild in 73 cases, at least focally moderate in 41 cases, and focally marked in 2 cases. Mitotic activity ranged from 0 to 124 mitotic figures/25 wide-field high power fields (WHPFs) (median mitotic count: 4 mitotic figures/25WHPFs). Twenty-five lesions had >10 mitotic figures/25WHPFs. A total of 16 cases (9%) had atypical mitotic figures. Osteoclastlike giant cells were detected in 39% of cases. Immunoreactivity was typically present for vimentin, NKI/C3, CD10, microphthalmia transcription factor, and PGP9.5, and focal reactivity was sometimes noted for smooth muscle actin and CD68. All tumors tested were negative for S100 protein, glial fibrillary acidic protein, and Melan A. The overwhelming majority of cases had involvement of the tissue margins. A complete follow-up record is available for 71 patients (40.3%) with follow-up intervals ranging from 3 years 2 months to 34 years 9 months (median: 17 y 9 mo). Limited or incomplete follow-up information is also available for an additional 14 patients with follow-up intervals ranging from weeks to approximately 10 years (median: 5 mo). Regrowth of tumor after biopsy or local excision was reported in 13 patients, one of whom had 2 recurrences. However, because of the nature of our consultation practice and a tendency for clinicians to specifically send us cases with a complex clinical course, this is believed an overestimation of the true recurrence rate. Neurothekeomas are morphologically and immunohistochemically distinct from true nerve sheath myxomas. An origin from fibroblastic cells with the ability to differentiate into myofibroblasts and a tendency to recruit histiocytic cells is postulated.

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.

Palmar-plantar fibromatosis in children and preadolescents: a clinicopathologic study of 56 cases with newly recognized demographics and extended follow-up information.

Palmar-plantar fibromatosis, the most common type of fibromatosis, is well recognized in the adult population, but many clinicians and pathologists are unfamiliar with the fact that children may also be affected by this process. This report describes the clinicopathologic findings in 56 cases of palmar-plantar fibromatosis in children and preadolescents. Our study group included 19 males and 37 females, ranging from 2 to 12 years of age at the time of their first surgical procedure (median age, 9 years). The patients typically presented with solitary, lobular or multilobular masses in the 0.5- to 2.5-cm size range. The preoperative duration of the lesions ranged from 1 month to 6 years, with 1 patient purportedly having clinical evidence of disease since birth. All but two of the initial lesions occurred on the plantar aspect of the feet, typically in the region of the arch. Only 2 patients presented with palmar disease. The tumors were usually painless, except when pressure was applied. Seven patients had a history of trauma, sometimes involving a foreign body. One patient presented with concurrent disease involving both feet, and 12 additional patients subsequently developed palmar-plantar fibromatosis in another extremity, knuckle pads on the hands, or had other clinical findings linked to this disease. A family history was available for 25 patients, and 11 individuals had relatives with palmar-plantar fibromatosis, and 4 others had relatives with a history that was either suspicious for palmar-plantar disease or positive for other disorders associated with this disease. Histologically, the tumors involved aponeurosis and commonly formed discontinuous, moderately cellular, nodular masses composed of spindled cells with intervening collagen. Mitotic counts for 79 separately submitted tumor specimens ranged from 0 to 31 mitotic figures per 25 wide-field high power fields (mean mitotic count, 3.4 mitotic figures per 25 wide-field high power fields). Eight tumor had > or =10 mitoses per 25 wide-field high power fields. All patients were initially managed by local excision, and in most of cases, histologic examination showed tumor extending to the tissue edge. Thirty-two of 38 patients (84.2%) with clinical follow-up, ranging from 4 months to 33 years (mean, 14 years 9 months; median, 16 years 1 month), had one (n = 16) or more (n = 16) local recurrence of their fibromatosis.

Nerve sheath myxoma: a clinicopathologic and immunohistochemical analysis of 57 morphologically distinctive, S-100 protein- and GFAP-positive, myxoid peripheral nerve sheath tumors with a predilection for the extremities and a high local recurrence rate.

This report describes the clinicopathologic findings in 57 cases of nerve sheath myxoma. Our study group included 34 males and 23 females, ranging from 8 to 72 years of age at the time of their first surgical procedure (mean, 36 years; median, 34 years). The patients typically presented with solitary, superficial, multinodular masses in the 0.5- to 2.5-cm size range. Eighty-six percent of cases occurred in the extremities, with the most common locations being the hand/fingers (n = 22), knee/pretibial region (n = 10), and ankle/foot (n = 7). Only 7 cases (12.3%) involved the trunk or head and neck region. The tumors were generally slow growing, and often, they were present for many years before surgical resection was sought. In the majority of instances, the lesions were painless. Histologically, the tumors involved the dermis and/or subcutis, and they formed distinct multinodular/multilobular masses with abundant myxoid matrix and a peripheral fibrous border. All cases had small epithelioid Schwann cells in corded, nested, and/or syncytial-like aggregates, a variable number of Schwann cells with a ring-like appearance, and scattered spindled and stellate-shaped Schwann cells. These cells often had cytoplasmic-nuclear invaginations, and they were immunoreactive for S-100 protein, glial fibrillary acidic protein, neuron specific enolase, and CD57. They were also bordered by collagen IV. Epithelial membrane antigen-positive perineurial cells were typically present in small numbers, primarily in the fibrous tissue directly adjacent to the myxoid nodules. CD34-positive intraneural fibroblasts were generally sparse. Mitotic figures were uncommon. All cases were initially managed by simple excision, and in almost all instances, tumor extended to the tissue edge. Follow-up information is available for 34 patients (follow-up range, 8 months to 28 years; median follow-up interval, 14 years 3 months). Sixteen patients (47%) had one (n = 11) or more (n = 5) local recurrence of their tumor, and 2 additional patients had findings suspicious for a recurrence. Nerve sheath myxomas are morphologically distinct peripheral nerve sheath tumors with a peak incidence in the fourth decade of life and a strong predilection for the extremities. These tumors have a relatively high local recurrence rate when managed by simple local excision. They appear to be unrelated to so-called cellular and mixed-type neurothekeomas.