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Christopher D M Fletcher

Publications and source records attributed to Christopher D M Fletcher.

At least 37 records · Page 2Linked to original sources
PubMed2005

Spindle cell rhabdomyosarcoma in adults.

The spindle cell variant of rhabdomyosarcoma (RMS) is uncommon and is most often encountered in the paratesticular region of children in whom it has a good prognosis. Only isolated cases in adulthood have been described. Sixteen cases of spindle cell RMS occurring in adults were retrieved from our files. Eleven patients were male and 5 were female. Patient age ranged from 18 to 79 years (median, 32 years). Tumor size varied from 1.5 to 35 cm (median, 6 cm). The head and neck region, including the oral cavity, parotid gland, nasopharynx, and nasal cavity, was the commonest affected area, accounting for >50% of the cases, followed by retroperitoneum, thigh, leg, subscapular area, hand, vulva, and paratesticular region (1 case each). Follow-up was available in 12 cases, ranging from 1 to 102 months (median, 16.5 months). Treatment modalities included surgery, chemotherapy, and radiation. Two patients died of uncontrolled local disease 13 and 27 months after diagnosis; 4 were alive without disease at 12, 17, 24, and 102 months, including 1 patient with metastasis to 10 of 50 pelvic lymph nodes at presentation; 3 are alive with localized disease at 16, 17, and 19 months; and 1 was followed for 6 months and showed persistent local disease. One patient is alive at 10 months after diagnosis with evidence of metastatic disease to bone, lungs, and breast. All the tumors showed long fascicles of spindle cells with elongated, vesicular nuclei and pale indistinct cytoplasm. Scattered spindled or polygonal rhabdomyoblasts with abundant brightly eosinophilic cytoplasm were present in all cases. In 3 cases, focal areas showed pseudovascular, sclerosing features. There were no round cell or pleomorphic areas. Positive immunohistochemical results were as follows: desmin (15 of 15 cases), myf-4 (12 of 12), fast myosin (7 of 9), myoglobin (2 of 3), HHF-35 (9 of 9), and SMA (11 of 14). One tumor was focally positive for keratins and EMA. All tumors were negative for caldesmon, S-100 protein, and GFAP. Spindle cell RMS is a rare neoplasm in adults and appears to have distinct clinicopathologic features when compared with cases occurring in the pediatric population. Specifically, it appears to be most common in the head and neck region, and although only limited follow-up is available so far, these lesions appear to have a more aggressive clinical course in adults.

Actins↗
PubMed2004

Targeted expression of human MYCN selectively causes pancreatic neuroendocrine tumors in transgenic zebrafish.

The zebrafish model organism has been used extensively for studies of genetic pathways in development, indicating its potential applicability to cancer. Here we show that targeted expression of MYCN in cells of the pancreatic islet induces neuroendocrine carcinoma. Four transgenic fish developed abdominal tumors between 4 and 6 months of age, and histologic analysis revealed lobulated arrangements of neoplastic cells with expression of the MYCN transgene. The tumors also expressed insulin mRNA, and pancreatic exocrine cells and ducts were identified within the neoplasms, indicating a pancreatic origin for the tumor. Transmission electron microscopy revealed cytoplasmic, endocrine-dense core granules, analogous to those found in human neuroendocrine tumors. Our studies establish a zebrafish transgenic model of pancreatic neuroendocrine carcinoma, setting the stage to evaluate molecular pathways downstream of MYCN in this vertebrate forward genetic model system.

Animals↗
PubMed2004

Liposarcoma subtypes: identification with computed tomography and ultrasound-guided percutaneous needle biopsy.

The purpose of the study was to evaluate the feasibility of image-guided percutaneous needle biopsy to enable specific subtype classification of liposarcoma in patients with previously diagnosed disease and compare the yield of fine and large needle techniques for each subtype. We reviewed the medical records and pathology reports of 69 fine (20 g) needle and large (15, 16 g) needle biopsies performed in 44 patients enrolled in a clinical trial evaluating the effect of a novel therapy for advanced liposarcoma in the abdomen and pelvis. Cytopathologists and surgical pathologists identified features that enabled them to classify the tumor into one of four subtypes: well differentiated, myxoid/round cell, pleomorphic and dedifferentiated. The pre-study open surgical biopsy was used as the standard for comparison. The diagnostic yield (proportion of biopsies with correct subtype diagnosis) of percutaneous biopsy for identifying all subtypes of liposarcoma was 81% (64% for fine needles and 73% for large needles alone). There was a significant association between pathologic subtype and the probability of a correct diagnosis (P=0.05). Accurate diagnostic subset classification of liposarcoma by percutaneous biopsy is feasible, although both fine and large needles should be used. Although these data cannot be extrapolated to primary diagnosis of liposarcoma, they are important for screening and subtyping of possible recurrence.

Adult↗
PubMed2004

Phase II study of the antiangiogenic agent SU5416 in patients with advanced soft tissue sarcomas.

PURPOSE: SU5416 (semaxanib) is a small molecule inhibitor of the vascular endothelial growth factor (VEGF) receptor-2 and KIT receptor tyrosine kinases. This Phase II study was conducted to investigate the safety and efficacy of SU5416 for patients with soft tissue sarcomas. EXPERIMENTAL DESIGN: Thirteen patients with locally advanced or metastatic soft tissue sarcomas were treated with SU5416 via intravenous infusion at a dose of 145 mg/m(2) twice weekly. In selected cases tumor biopsies were taken before and after 2 months of treatment. RESULTS: The median progression-free survival was 1.8 months. Median overall survival was 22.8 months. No objective tumor responses were observed. There was evidence of shorter survival among patients with high baseline urine VEGF levels (P = 0.04). No grade 4 toxicities were observed. The most common grade 3 toxicities were headache and thrombosis. Other less serious toxicities included fatigue, nausea, and abdominal pain. The median systolic blood pressure increased from 118 mmHg at baseline to 133 after 1 month of treatment (P = 0.01). Post-treatment tumor biopsies showed no significant decreases in VEGF receptor phosphorylation compared with baseline in 3 evaluable patients. One patient with gastrointestinal stromal tumor who had rapid progression during SU5416 treatment was subsequently treated with another KIT inhibitor, imatinib mesylate, and had a partial response lasting >36 months. CONCLUSIONS: SU5416 was relatively well tolerated but did not demonstrate significant antitumor activity against advanced soft tissue sarcoma. Correlative studies suggest that VEGF receptor or KIT inhibition was incomplete in at least some cases, providing a possible explanation for the observed lack of activity.

Adult↗
PubMed2004

Protein Kinase C theta (PKCtheta) expression and constitutive activation in gastrointestinal stromal tumors (GISTs).

KIT expression is a key diagnostic feature of gastrointestinal stromal tumors (GISTs), and virtually all of the GISTs express oncogenic forms of the KIT or PDGFRA receptor tyrosine kinase proteins, which serve as therapeutic targets of imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). However, KIT expression can be low in PDGFRA-mutant GISTs, increasing the likelihood of misdiagnosis as other types of sarcoma. We report that the signaling intermediate protein kinase C theta (PKCtheta) is a diagnostic marker in GISTs, including those that lack KIT expression and/or contain PDGFRA mutations. PKCtheta is strongly activated in most GISTs and hence may serve, along with KIT/PDGFRA, as a novel therapeutic target.

Enzyme Activation↗
PubMed2004

Mechanisms of oncogenic KIT signal transduction in primary gastrointestinal stromal tumors (GISTs).

Most gastrointestinal stromal tumors (GISTs) express constitutively activated forms of the KIT receptor tyrosine kinase protein, resulting from oncogenic mutations in the extracellular, juxtamembrane, or kinase domains. KIT oncoproteins are detected early in GIST tumorigenesis, and most GIST patients respond well to treatment with the KIT kinase inhibitor imatinib mesylate (STI571, Gleevec). However, GISTs can develop resistance to imatinib, and additional therapeutic strategies are needed. Little is known about oncogenic KIT signal transduction in GISTs, and whether the type of KIT mutation accounts for selective activation of downstream signaling intermediates. We therefore evaluated KIT downstream signaling profiles in 15 primary GISTs with mutations in KIT exons 9, 11, 13, and 17, and in two human GIST cell lines. All GISTs showed constitutive phosphorylation at KIT tyrosine residues Y703 and Y721. Additionally, most GISTs showed activation of MAPK p42/44, AKT, S6K, STAT1, and STAT3. STAT5 and JNK were not demonstrably activated in any GIST. Using GIST in vitro models, we showed that activation of MAPK p42/44, AKT, and S6K was KIT dependent, whereas STAT1 and STAT3 phosphorylation was only partially dependent on KIT activation. Correlation of activated signaling pathways with the type of KIT mutation revealed low levels of AKT phosphorylation in exon 9 mutant GISTs in contrast to a subset of GISTs with exon 11 mutations. However, additional factors are likely to modify the engagement of signaling pathways in GISTs as suggested by the fact that four GISTs with identical KIT exon 9 mutations had differential activation of MAPK p42/44 and STAT proteins. In summary, in this first report on KIT signal transduction in primary GISTs and GIST cell lines, we identified pathways that are constitutively activated in a KIT-dependent manner and therefore warrant further study as molecular targets in GISTs.

Apoptosis↗
PubMed2004

The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma.

Low-grade fibromyxoid sarcoma (LGFMS) is a variant of fibrosarcoma that was recognized as a distinct tumor entity only quite recently. We previously described a translocation, t(7;16)(q33;p11), that resulted in a fusion of the FUS and CREB3L2 (also known as BBF2H7) genes in two soft tissue tumors that fulfilled morphologic criteria for LGFMS. To delineate the spectrum of tumors that may harbor the FUS/CREB3L2 gene, we selected 45 low-grade spindle cell sarcomas for reverse transcriptase polymerase chain reaction (RT-PCR) and/or fluorescence in situ hybridization (FISH) analyses; none of these tumors had originally been diagnosed as LGFMS. Furthermore, also included were two benign soft tissue tumors and nine high-grade sarcomas with supernumerary ring chromosomes or 7q3 rearrangement and three tumors diagnosed as LGFMS prior to the genetic analysis. Of the 59 tumors analyzed, 12 were FUS/CREB3L2-positive, all of which were diagnosed at histopathologic re-examination as being LGFMS, of both the classical subtype and the subtype with giant collagen rosettes. The breakpoints in the fusion transcripts were always in exons 6 or 7 of FUS and exon 5 of CREB3L2. The results indicated that FUS/CREB3L2 is specifically associated with LGFMS and that RT-PCR or FISH analysis may be useful for the differential diagnosis.

Adolescent↗
PubMed2004

Cutaneous myoepithelioma: a clinicopathologic and immunohistochemical study of 14 cases.

Analogous to mixed tumors of salivary glands (" pleomorphic adenomas" ), cutaneous mixed tumors (" chondroid syringomas" ) contain a ductal (epithelial) component and a variably prominent myoepithelial component. Tumors showing purely myoepithelial differentiation (myoepitheliomas) have only recently been recognized to arise in the dermis, and to date very few cases have been described. To characterize these tumors further, 14 cutaneous myoepithelial tumors were retrieved from the authors' consult files. Eleven patients were male and 3 were female; their median age was 22.5 years (range, 10 to 63 years), and 7 patients were between 10 and 20 years old. Tumor size ranged from 0.5 to 2.5 cm (mean, 1.1 cm). Most tumors arose on the extremities: 6 on the upper limbs, 6 on the lower limbs, and 1 each on the back and nose. Ten tumors were limited to the dermis, and 5 also extended into superficial subcutis. Thirteen tumors were myoepitheliomas (lacking ductal differentiation), and 1 tumor was a myoepithelial carcinoma (exhibiting severe cytological atypia and a high mitotic rate). Histologically, 7 tumors were solid, composed of ovoid to spindled, histiocytoid, or epithelioid cells with no significant stroma, and 7 were predominantly lobulated, with cords or nests of epithelioid, plasmacytoid, or spindled cells with a variably reticular architecture and a chondromyxoid or collagenous/hyalinized stroma. One tumor was composed solely of plasmacytoid (hyaline) cells, and 1 exhibited extensive adipocytic differentiation. Among the 13 myoepitheliomas, mitoses ranged from 0 to 6 per 10 high-power fields (HPFs) (mean, 1.5); 8 tumors contained no mitoses. The myoepithelial carcinoma had 39 mitoses per 10 HPFs. By immunohistochemistry, all cases were reactive for epithelial markers (keratins and/or epithelial membrane antigen [EMA]); 13 of 14 (93%) expressed S-100 protein, 10 of 11 expressed (91%) calponin, 11 of 14 (79%) expressed EMA, 9 of 14 (64%) expressed keratins, 8 of 14 (57%) expressed smooth muscle actin, 7 of 14 (50%) expressed glial fibrillary acidic protein, 3 of 11 (27%) expressed p63, and 1 of 6 (17%) expressed desmin. All 5 cases without keratin staining were diffusely positive for EMA, and all of these cases showed a solid growth pattern. Follow-up was available for 8 patients (median follow-up, 40 months; range, 6 months to 9 years); 3 tumors (38%) recurred locally, and 1 tumor (13%) also metastasized to the lymph nodes. The case that resulted in recurrence and metastasis had the highest mitotic rate (6 per 10 HPFs) of the cytologically benign tumors. Follow-up information was not available for the myoepithelial carcinoma. This study suggests that approximately 50% of cutaneous myoepitheliomas are distinctive lesions composed of a solid proliferation of cells with abundant eosinophilic syncytial cytoplasm, which often lack immunostaining for keratin, whereas the remainder demonstrate focally reticular architecture and myxoid stroma or plasmacytoid cells, similar to their counterparts in salivary gland and soft tissue. Whereas most cutaneous myoepitheliomas behave in a benign fashion, there is apparently a significant risk for local recurrence but a low metastatic potential.

Adolescent↗
PubMed2004

Activation of the GLI oncogene through fusion with the beta-actin gene (ACTB) in a group of distinctive pericytic neoplasms: pericytoma with t(7;12).

Activation of the GLI oncogene is an important step in the sonic hedgehog signaling pathway, and leads to, eg, tissue-specific cell proliferation during embryogenesis. GLI activity in adult tissues is restricted, but has been identified in various neoplasms, as a result of mutations in the PTCH (patched) or SMOH (smoothened) genes, encoding components of the sonic hedgehog pathway, or by amplification of GLI. Herein, we present a new mechanism of GLI activation through fusion with the beta-actin gene (ACTB) in five histologically distinctive soft tissue tumors showing a t(7;12)(p21-22;q13-15) and a pericytic phenotype. Each was composed of a perivascular proliferation of monomorphic short spindle cells that stained positively for smooth muscle actin and laminin and that showed pericytic features by electron microscopy. To date, with a median follow-up of 24 months, none has behaved in an aggressive manner. Molecular genetic analysis showed that the translocation in all cases resulted in a fusion transcript including the 5'-part of ACTB and the 3'-part of GLI. The DNA-binding zinc finger domains of GLI were retained in the fusion transcripts and it is likely that the replacement of the promoter region of GLI with that of the ubiquitously expressed ACTB gene leads to deregulation of GLI expression and its downstream target genes.

Actins↗
PubMed2004

Cutaneous epithelioid angiomatous nodule: a distinct lesion in the morphologic spectrum of epithelioid vascular tumors.

Cutaneous epithelioid vascular proliferations comprise a morphologic spectrum ranging from benign, reactive to frankly malignant conditions. We present a group of morphologically distinct epithelioid vascular lesions in the skin that defy classification according to current criteria. Clinically, the lesions presented as single (14/15) or multiple (1/15) small (< 1.5 cm, median = 0.5 cm) erythematous to bluish nodules or papules of short duration (weeks to months) without gender predilection (M:F = 1:1). Age distribution ranged from 15 to 79 years (median: 37). Lesions were predominantly located on the trunk (8/15) but also involved the extremities (5/15), face (1/15), and nasal mucosa (1/15). No patient was immunocompromised. Treatment was simple surgical excision. Histologically, the lesions were located superficially in dermis (or submucosa) and consisted of a circumscribed, unilobular, mainly solid proliferation of large polygonal epithelioid endothelial cells with vesicular nuclei and conspicuous nucleoli. Cytoplasm was abundant and contained frequent intracytoplasmic vacuoles. Nuclear atypia was absent. Mitotic figures (up to 5/10HPF) were observed in 8 lesions. Formation of endothelial-lined channels was a focal but constant feature. Also noted were adjacent dilated dermal vessels (8/15), hemosiderin deposition (6/15), and mild fibrosis (9/15). The lesion was accompanied by a chronic inflammatory infiltrate with a lymphoplasmacytic component (14/15), most pronounced at the periphery of the lesion, and varying numbers of eosinophils scattered throughout the lesion (12/15). Eosinophils were conspicuous in only 4 cases. Epidermal hyperplasia was present in 11 cases. By immunohistochemistry, lesional cells stained positively for at least one endothelial marker. Clinical follow-up (median = 30 months) showed no recurrence or metastases. Epithelioid angiomatous nodule is a benign, likely reactive cutaneous lesion in the clinical and morphologic spectrum of epithelioid vascular proliferations. It differs from conventional epithelioid hemangioma both in its clinical presentation with predominant involvement of trunk and extremities as well as its histologic features, which more closely resemble epithelioid angiosarcoma.

Adolescent↗
PubMed2004

Distinctive dermal clear cell mesenchymal neoplasm: clinicopathologic analysis of five cases.

Dermal clear cell tumors are not common. This group of lesions is comprised primarily of clear cell adnexal lesions, balloon cell melanocytic lesions, and metastatic clear cell carcinomas. We report the clinicopathologic features of five cases of a novel dermal clear cell neoplasm that appears mesenchymal in nature. The affected patients included 3 men and 2 women ranging in age from 38 to 70 (median, 45 years). All the lesions occurred on the lower limb. Clinically described as smooth cutaneous nodules, size ranged from 0.5 to 2.5 cm in greatest dimension and the lesions were present from weeks to 5 years prior to excision. Situated in the reticular dermis, the tumors usually extended to involve the subcutis with sparing of the papillary dermis. The tumors were composed of large optically clear cells with vesicular nuclei. The lesions entrapped adnexal structures and thin dermal collagen fibers. Mitoses were rare (less than 1 per 25 hpf). A single case showed more pleomorphic nuclei as well as quite frequent mitoses and was considered of uncertain biologic potential. Immunohistochemistry revealed reactivity only for NKI-C3 (5/5 cases), CD68 (2/5 cases), and vimentin (2/3 cases); melanocytic, epithelial, and lymphoid markers were uniformly negative. All five lesions were locally excised; the more pleomorphic and mitotically active lesion was widely re-excised and given subsequent radiation therapy. In follow-up ranging from 1.5 to 11 years (median, 5.5 years), none of these lesions has recurred. These tumors appear to be mesenchymal in nature, but their precise line of differentiation is unknown. Recognition of these lesions is important to avoid confusion with better-known malignant neoplasms.

Adult↗
PubMed2004

KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications.

The diagnosis of gastrointestinal stromal tumor (GIST) is currently based on morphologic features and immunohistochemical demonstration of KIT (CD117). However, some tumors (in our estimation approximately 4%) have clinicopathologic features of GIST but do not express KIT. To determine if these lesions are truly GISTs, we evaluated 25 tumors with clinical and histologic features typical of GIST, but with negative KIT immunohistochemistry, for KIT and PDGFRA mutations using DNA extracted from paraffin-embedded tissue. Most tumors originated in the stomach (N = 14) or omentum/mesentery (N = 5). The neoplasms were composed of epithelioid cells (13 cases), admixed epithelioid and spindle cells (8 cases), or spindle cells (4 cases). Absence of KIT expression was confirmed by immunoblotting in 5 cases. Tumor karyotypes performed in 4 cases were noncomplex with monosomy 14 or 14q deletion, typical of GIST. Mutational analysis revealed PDGFRA and KIT mutations in 18 and 4 tumors, respectively, whereas 3 tumors did not have apparent KIT or PDGFRA mutations. The PDGFRA mutations primarily involved exon 18 (N = 15) and included 11 tumors with missense mutation in codon 842 (PDGFRA D842V or D842Y). In conclusion, a small subset of GISTs with otherwise typical clinicopathologic and cytogenetic features do not express detectable KIT protein. When compared with KIT-positive GISTs, these KIT-negative GISTs are more likely to have epithelioid cell morphology, contain PDGFRA oncogenic mutations, and arise in the omentum/peritoneal surface. Notably, some KIT-negative GISTs contain imatinib-sensitive KIT or PDGFRA mutations; therefore, patients with KIT-negative GISTs should not, a priori, be denied imatinib therapy.

Adult↗
PubMed2004

Distinctive prepubertal vulval fibroma: a hitherto unrecognized mesenchymal tumor of prepubertal girls: analysis of 11 cases.

Eleven cases of a distinctive previously unrecognized mesenchymal tumor that arises in the vulvar region in the prepubertal years are described. The tumors presented in the vulva (8 cases arising from labia majora) of prepubertal girls (range, 4-12 years; median, 8 years). The preoperative diagnoses were labial mass or swelling, not otherwise specified in 3 cases, hemangioma in 2 cases, lipoma in 2 cases, and lymphangioma and Bartholin cyst/lymphedema in 1 case each. The tumors were unilateral, ill defined, located in the submucosa or subcutaneous tissue, and ranged in size from 2.0 to 8.0 cm in maximum dimension. Microscopically, they were poorly marginated, hypocellular neoplasms composed of bland spindle-shaped cells in a variably collagenous to edematous or myxoid stroma, diffusely infiltrating between preexisting normal vascular, adipose, and neural tissues. No cytologic atypia was identified. Mitotic activity was minimal with no abnormal mitotic figures. The tumor cells were immunoreactive for CD34 (8 of 9 cases) but not for smooth muscle actin, desmin, and S-100 protein. Treatment was by local excision. From the follow-up data available for 9 patients, 3 patients showed locally recurrent tumor after 4, 6, and 13 months, respectively, of which the second case showed a second recurrence 18 months after the first excision. The term "prepubertal vulval fibroma" is suggested because it reflects the distinct features of this seemingly unique, previously uncharacterized, site- and age-specific mesenchymal tumor.

Child↗
PubMed2004

Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy.

Histiocytic sarcoma is a rare malignant neoplasm that occurs in lymph nodes, skin, and the gastrointestinal tract. Many previously published cases were likely misdiagnosed examples of non-Hodgkin lymphoma. Only small numbers of bona fide examples exist in the world literature; cases arising primarily at extranodal sites are not well described and often seem to go unrecognized. To characterize these tumors further, 14 extranodal histiocytic sarcomas were analyzed. Hematoxylin and eosin sections were reexamined, immunohistochemistry was performed, and clinical details were obtained from referring hospitals. Eight patients were female and 6 male (median age, 55 years; range, 15-89 years). All patients presented with a solitary mass, ranging in size from 1.8 to 12 cm (median 6.8 cm). Seven tumors arose in soft tissue (6 lower limb; 1 upper limb), 5 in the gastrointestinal tract (1 involving both stomach and colon, 1 ileum, 2 rectum, 1 anus), 1 in the nasal cavity, and 1 in the lung. Three gastrointestinal tract tumors also involved regional lymph nodes, and 1 involved the liver. Most cases had infiltrative margins. The tumors were generally composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin, and large nucleoli. Binucleated cells were common, and 6 cases contained tumor giant cells. Mitoses ranged from 1 to 64 per 10 HPF (median 11 per 10 HPF). Necrosis was present in 8 cases. Nearly all tumors showed a striking inflammatory infiltrate, most often of neutrophils or lymphocytes. All cases were reactive for LCA, CD45RO, and CD68 (KP1 and PG-M1); 13 of 14 (93%) expressed CD4, 12 of 14 (86%) lysozyme, 8 of 10 (80%) CD31, 7 of 14 (50%) S-100 protein, and 5 of 14 (36%) focal CD1a. Two tumors showed weak, focal cytoplasmic positivity for CD30, and 1 for epithelial membrane antigen. The tumors were negative for ALK-1, CD21, CD35, CD3, CD20, CD34, myeloperoxidase, HMB-45, and keratins. Gastrointestinal tract cases were negative for c-kit and desmin. Six patients were treated with postoperative radiation and 7 with chemotherapy (CHOP or ProMACE-MOPP). Follow-up was available for 10 patients (median, 24 months; range, 4 months to 11 years). Two tumors recurred locally, and 5 patients developed distant spread: 3 to lymph nodes, 1 to lung, and 1 to bone. At the last follow-up, 2 patients have died of disseminated disease, 4 and 5 months following initial diagnosis. The patients who died thus far had the largest primary tumors. Histiocytic sarcoma may arise primarily in soft tissue and shows reproducible histologic features, including abundant eosinophilic cytoplasm and a prominent inflammatory infiltrate. Metastatic carcinoma, metastatic melanoma, and large cell non-Hodgkin lymphomas should be excluded by immunohistochemistry. Histiocytic sarcoma has the potential for an aggressive clinical course, most often with lymph node involvement. However, a subset of cases presenting with clinically localized disease have a favorable long-term outcome. Tumor size may be a prognostic factor.

Adolescent↗
PubMed2004

Pleomorphic liposarcoma: clinicopathologic analysis of 57 cases.

Pleomorphic liposarcoma is an uncommon form of liposarcoma that only recently has been properly characterized. A series of 57 cases is presented. Patient age at presentation ranged from 27 to 95 years (median, 54 years), and there was a slight male predilection (male/female ratio = 1.2:1). Tumors most frequently involved the lower limb (47% of cases) or upper limb (18%). Other anatomic sites, including trunk (14%), retroperitoneum (7%), head and neck (5%), abdomen/pelvis (5%), and spermatic cord (4%), were less frequently involved. Tumor size ranged from 1.5 to 21 cm (median, 8 cm), with deep (subfascial) locations (39 cases) being more frequent than subcutaneous (11 cases) or dermal sites (5 cases). All lesions showed features of pleomorphic sarcoma and at least focally contained typical multivacuolated lipoblasts. Although there was considerable overlap, tumors fell into three broad categories: high-grade pleomorphic/spindle cell sarcoma with scattered lipoblasts or sheets of lipoblasts (60%), high-grade pleomorphic sarcoma with epithelioid areas and scattered lipoblasts (28%), and intermediate- to high-grade sarcoma predominantly resembling myxofibrosarcoma except for the presence of lipoblasts (12%). Immunohistochemistry revealed focal staining for smooth muscle actin in 13 of 29 cases (45%), S-100 protein positivity in lipoblasts in 15 of 45 cases (33%), focal staining for keratin in 6 of 28 cases (21%), including 5 of 13 (38%) with epithelioid morphology, and focal staining for desmin in 4 of 30 cases (13%). Follow-up data, available in 50 patients (88%) (median, 33 months), showed local recurrence in 34% of patients, systemic metastases in 32%, and tumor-related death in 32%. Only 2 of the 16 superficial (dermal or subcutaneous) lesions metastasized. Five-year overall, local recurrence-free, metastasis-free, and disease-free survivals were 63%, 58%, 58%, and 39%, respectively. By univariate analysis, central (nonextremity) location, deep situation, tumor size > or =10 cm, mitotic rate > or =10 per 10 HPF, necrosis, and epithelioid morphology were associated with a worse prognosis. However, by multivariate analysis, only age > or =60 years, central location, tumor size, and mitotic rate remained independent predictors for an adverse outcome. By multivariate analysis, wide local excision or amputation and postoperative radiotherapy protected against local recurrence.

Adult↗
PubMed2004

Cellular angiofibroma: clinicopathologic and immunohistochemical analysis of 51 cases.

Cellular angiofibroma is a recently described histologically distinctive benign mesenchymal neoplasm composed of 2 principal components, the cellular spindle cell component and prominent stromal blood vessels. Cases in males have sometimes been called "angiomyofibroblastoma-like tumor." We describe a series of 51 cases of cellular angiofibroma to further characterize its clinicopathologic and immunohistochemical features. There were 26 women and 25 men, ranging in age from 22 to 78 years (mean 53.5, median 52 years). Men tended to be older than women. Tumor size ranged from 0.6 to 25.0 cm (overall median size 3.9 cm, median in women 2.7 cm, median in men 6.7 cm). Most common sites were the vulvovaginal region (22 cases) and the inguinoscrotal region (19 cases). Preoperative duration (known for 25 patients) ranged from 1 week to 5 years, with presentation as a painless mass, except for 1 case each with intermittent genital bleeding and a painful mass. Most lesions were located primarily in subcutaneous tissue. Most cases were grossly well marginated. Two cases showed foci of hemorrhage and 1 case showed foci of necrosis. Microscopically, 41 tumors were well circumscribed, and 2 tumors infiltrated into the surrounding tissue. All tumors consisted of bland, spindle-shaped cells, short bundles of wispy collagen and numerous small- to medium-sized thick-walled vessels. Intralesional fat was present in 12 cases (6 female and 6 male cases). Mild cytologic atypia (5 cases) and frequent mitoses (3 cases) were infrequent; significant nuclear atypia and abnormal mitoses were absent. By immunohistochemistry, 29 of 48 tumors (60%) expressed CD34, 10 of 48 (21%) SMA, 4 of 48 (8%) desmin, but none expressed S-100 protein. Follow-up information was available for 40 patients (range 4-168 months; mean 31.2 months) and no patient has developed recurrence or metastasis to date.

Adult↗