Leona A Doyle

Harvard Medical School, Boston, Massachusetts, United States

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Publications (30)114.65 Total impact

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    ABSTRACT: Epithelioid benign fibrous histiocytoma, also known as 'epithelioid cell histiocytoma,' has traditionally been considered a morphologic variant of cutaneous fibrous histiocytoma (dermatofibroma). In addition to its characteristic epithelioid cytomorphology, several phenotypic differences suggest that epithelioid fibrous histiocytoma may differ biologically from other variants. Recently, ALK rearrangement was described in two cases of epithelioid fibrous histiocytoma and separately in two cases reported as 'atypical' fibrous histiocytoma (with epithelioid features), with corresponding ALK expression detectable by immunohistochemistry. The goals of this study were to determine the frequency of ALK expression by immunohistochemistry in epithelioid fibrous histiocytoma, to determine its value for the diagnosis of epithelioid fibrous histiocytoma among variants and other histologic mimics, and to evaluate ALK gene rearrangement in epithelioid fibrous histiocytoma. ALK protein expression was evaluated in whole tissue sections from 33 epithelioid fibrous histiocytomas, 41 other cases of fibrous histiocytoma (11 conventional and 10 each cellular, atypical, and aneurysmal types), 10 cutaneous syncytial myoepitheliomas, and 5 atypical fibroxanthomas, using a mouse anti-ALK monoclonal antibody. Fluorescence in situ hybridization (FISH) was performed using break-apart probes. In total, 29/33 (88%) cases of epithelioid fibrous histiocytoma showed diffuse cytoplasmic ALK expression. Staining was moderate to strong in intensity in all cases except one, which showed diffuse weak expression. All other tumor types were negative for ALK expression. FISH demonstrated ALK rearrangement in all ALK-immunoreactive cases evaluated (n=13), and not in one ALK expression-negative epithelioid fibrous histiocytoma successfully examined. In conclusion, the majority of epithelioid fibrous histiocytomas demonstrate ALK expression and ALK gene rearrangement. ALK expression is not seen in other variants of fibrous histiocytoma, providing a useful diagnostic tool to distinguish epithelioid fibrous histiocytoma from most histologic mimics. The expression of ALK suggests that epithelioid fibrous histiocytoma is a biologically distinct tumor type, unrelated to conventional fibrous histiocytoma and histologic variants.Modern Pathology advance online publication, 10 April 2015; doi:10.1038/modpathol.2015.49.
    Modern Pathology 04/2015; DOI:10.1038/modpathol.2015.49 · 6.36 Impact Factor
  • Leona A. Doyle
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    ABSTRACT: Recent insights into the pathogenesis of various soft tissue tumors, along with the identification of recurrent molecular alterations characteristic of specific tumor types, have resulted in the development of many diagnostically useful immunohistochemical markers. In some cases, expression of these markers is significantly associated with distinctive clinical and histologic features, which may impart prognostic or predictive information. This review outlines new diagnostic immunohistochemical markers in soft tissue tumor pathology, emphasizing their utility in clinical practice and potential pitfalls, molecular correlates and clinical associations. Copyright © 2015 Elsevier Inc. All rights reserved.
    Seminars in Diagnostic Pathology 02/2015; DOI:10.1053/j.semdp.2015.02.012 · 1.80 Impact Factor
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    ABSTRACT: Increasingly, tumors are being analyzed for a variety of mutations and other genomic changes, with the goal of guiding personalized therapy and directing patients to appropriate clinical trials based on genotype, as well as identifying previously unknown genomic changes in different tumor types and thereby providing new insights into the pathogenesis of human cancers. Next-generation sequencing (NGS) is a powerful research tool now gaining traction in the clinic. In this report, we demonstrate the utility of NGS assays in providing diagnostic information when evaluating tumor specimens. This is illustrated by a case previously thought to represent an atypical carcinoid tumor, in which an EWSR1-ERG translocation was detected during next generation sequencing using a hybrid capture approach, leading to a revised diagnosis of Ewing sarcoma. The role of translocation detection in these assays is also discussed.
    Cancer Genetics 08/2014; DOI:10.1016/j.cancergen.2014.08.004 · 2.42 Impact Factor
  • Leona A. Doyle
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    ABSTRACT: The 2013 World Health Organization Classification of Tumors of Soft Tissue and Bone incorporates changes in tumor classification, as well as new genetic insights into the pathogenesis of many different tumor types that have emerged over the 11 years since the publication of the prior volume. This article reviews changes in the classification of soft tissue and bone sarcomas as well as tumors of intermediate biologic potential in the 2013 World Health Organization volume, new molecular insights into these tumors, and associated surgical and clinical implications. Cancer 2014. © 2014 American Cancer Society.
    Cancer 06/2014; 120(12). DOI:10.1002/cncr.28657 · 4.90 Impact Factor
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    Clinical Cancer Research 05/2014; 19(19_Supplement):A11-A11. DOI:10.1158/1078-0432.OVCA13-A11 · 8.19 Impact Factor
  • Leona A Doyle, Jason L Hornick
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    ABSTRACT: Mastocytosis encompasses a group of clinically and pathologically heterogeneous disorders most commonly involving the skin, which typically takes the form of urticaria pigmentosa. Mastocytosis may also involve other organs, most often bone marrow, followed by gastrointestinal tract, liver, spleen, and lymph nodes. The presence of extracutaneous involvement by mastocytosis is a major diagnostic criterion for systemic disease. However, mast cell infiltrates are often subtle in skin and extracutaneous organs, and the histologic features of mastocytosis at different anatomic sites may be variable. This article reviews the pathologic features and clinical correlates of mastocytosis involving skin and other extramedullary sites.
    Immunology and allergy clinics of North America 05/2014; 34(2):323-339. DOI:10.1016/j.iac.2014.01.010 · 2.22 Impact Factor
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    ABSTRACT: Cutaneous fibrous histiocytoma (FH) is a common mesenchymal neoplasm. Metastasis is rare, disproportionately occurring among the aneurysmal, cellular, atypical, and deep variants. We determined whether DNA copy number changes occurred in atypical FH (AFH), and whether they were similar to those in metastasizing FH (MetFH) and benign cellular FH (CFH). Five primary tumors of MetFH were evaluated by array-based comparative genomic hybridization analysis, with tissue from local recurrences and lung metastases in 2 and 2 patients, respectively. Seven indolent AFH and 5 CFH were identified for comparison. Substantial differences between the groups were found both in the frequency of chromosomal aberrations (higher among MetFH and absent or solitary in CFH) and array-based comparative genomic hybridization profiles (frequent gains of 7 and 8q and losses of Xq in MetFH; recurrent losses of chromosomes 9 and 22 in AFH; isolated loss of 5q and gain in chromosome 20 in 2 CFH). Fatal MetFH cases (2 of 5 cases) exhibited the highest rate of chromosomal aberrations. This study included a small sample size with a short-term follow-up. Benign CFH, indolent AFH, and MetFH represent distinct biological entities within the spectrum of FH; array-based comparative genomic hybridization may be a tool in recognizing FH cases with metastatic potential and increasingly aggressive behavior.
    Journal of the American Academy of Dermatology 04/2014; 71(2). DOI:10.1016/j.jaad.2014.03.015 · 5.00 Impact Factor
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    ABSTRACT: Counting mast cells in gastrointestinal (GI) mucosal biopsies is becoming an increasingly common practice. The primary reason for this exercise is to evaluate for possible involvement by systemic mastocytosis (SM). However, the features of mastocytosis in GI biopsies are not well described. In addition, recent studies have suggested that increased mast cells may be involved in the pathogenesis of some cases of diarrhea-predominant irritable bowel syndrome (IBS); the term "mastocytic enterocolitis" has been proposed for such cases. As the baseline mast cell density in colonic biopsies from normal patients has not been established in large cohorts, there is no widely accepted threshold for what constitutes increased mucosal mast cells. The aims of this study were (1) to determine the utility of GI biopsies for the diagnosis of SM, (2) to characterize the clinical, histologic, and immunohistochemical features of mastocytosis in the GI tract, (3) to determine mast cell density in normal colonic mucosa from a large cohort of asymptomatic patients, and (4) to compare these findings with those from patients with diarrhea-predominant IBS. Twenty-four patients with SM involving the GI tract, 100 asymptomatic patients, and 100 patients with IBS (the latter 2 groups with histologically normal colonic biopsies) were included. For the mastocytosis group, 107 biopsies (70 involved by mastocytosis; 67 mucosal, 3 liver) from 20 women and 4 men were evaluated (median age 59 y). The most commonly involved site was the colon (19 patients, 95%), followed by ileum (86%), duodenum (80%), and stomach (54%). In 16 cases (67%), the first diagnosis of SM was made on the basis of GI biopsies. Seventeen patients had documented cutaneous mastocytosis. Fifteen of 17 patients who underwent bone marrow biopsy had marrow involvement by SM. Eighteen patients had indolent disease, and 6 had aggressive disease (including all 3 with liver involvement). The most common GI symptom was diarrhea, followed by abdominal pain, nausea, weight loss, bloating, vomiting, or reflux. Liver disease presented with hepatomegaly and ascites. Endoscopic abnormalities (observed in 62%) included erythema, granularity, and nodules. Histologically, involved biopsies were characterized by infiltrates of ovoid to spindle-shaped mast cells in aggregates or sheets in the lamina propria, sometimes forming a confluent band underneath the surface epithelium; 25% of biopsies had only focal involvement (single aggregate). Prominent eosinophils were seen in 44% of involved colonic/ileal biopsies and 16% of duodenal biopsies. Mast cells were highlighted by diffuse membranous staining for KIT and CD25. In the nonmastocytosis groups, all biopsies contained singly dispersed mast cells with no aggregates. The mean highest mast cell counts (in a single high-power field) for asymptomatic patients and IBS patients were 26 (range, 11 to 55) and 30 (range, 13 to 59), respectively. In summary, GI (especially colonic) biopsies can establish a diagnosis of SM in patients with GI symptoms. GI involvement is usually subtle and is often associated with prominent eosinophils, which may obscure the mast cell infiltrate. KIT and CD25 are invaluable markers for the diagnosis. Mast cell density in colonic mucosa from asymptomatic patients is highly variable. Although patients with diarrhea-predominant IBS on average have mildly increased mast cells, the overlap in range with that of control patients is too great for this difference to be clinically useful. These findings argue against the utility of counting GI mucosal mast cell in patients with chronic diarrhea.
    The American journal of surgical pathology 03/2014; 38(6). DOI:10.1097/PAS.0000000000000190 · 4.59 Impact Factor
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    ABSTRACT: A recurrent intrachromosomal rearrangement on chromosome 12q in solitary fibrous tumor leads to the formation of a NAB2-STAT6 fusion oncogene. As a result, nuclear expression of the cytoplasmic transcription factor STAT6 is found in solitary fibrous tumor and serves as a useful diagnostic marker. STAT6 is located in 12q13, a region containing well-characterized oncogenes that are commonly amplified in dedifferentiated liposarcoma; we have previously reported that STAT6 is expressed in a subset of dedifferentiated liposarcoma. The aim of this study was to determine the frequency of STAT6 expression in dedifferentiated liposarcoma and the underlying genetic mechanism. STAT6 protein expression was analyzed by immunohistochemistry in a well-characterized series of 35 previously unpublished cases of dedifferentiated liposarcoma, all with nuclear MDM2 and/or CDK4 expression by immunohistochemistry and/or cytogenetic features of dedifferentiated liposarcoma. FISH for STAT6 was performed in all cases with STAT6 expression, and a subset of control cases without STAT6 expression. In total 4/35 cases (11%) showed STAT6 expression (three with multifocal staining of moderate to strong intensity and one with weak focal staining). FISH demonstrated amplification of STAT6 in all cases positive for STAT6 by immunohistochemistry; in contrast, FISH performed on four STAT6-negative dedifferentiated liposarcomas demonstrated no STAT6 amplification (P=0.0286). Of the four STAT6 amplified cases, three patients were male and one was female, ranging in age from 51 to 76 years. Tumors were located in the mediastinum (n=2), paratesticular soft tissue (n=1), and perirenal soft tissue (n=1). Three patients received pre-operative chemotherapy +/- radiation therapy. In conclusion, STAT6 is amplified in a subset of dedifferentiated liposarcoma, resulting in STAT6 protein expression that can be detected by immunohistochemistry and may be a potential pitfall in the differential diagnosis of dedifferentiated liposarcoma and solitary fibrous tumor. These findings suggest a role for STAT6-mediated transcriptional activity in some cases of dedifferentiated liposarcoma and highlight the genomic complexity and heterogeneity of dedifferentiated liposarcoma.Modern Pathology advance online publication, 24 January 2014; doi:10.1038/modpathol.2013.247.
    Modern Pathology 01/2014; DOI:10.1038/modpathol.2013.247 · 6.36 Impact Factor
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    ABSTRACT: The NAB2-STAT6 fusion was recently identified as a consistent finding in solitary fibrous tumour (SFT), resulting in nuclear expression of the carboxy-terminal part of STAT6. Gene expression studies of SFT revealed high expression of the GRIA2 gene (GLUR2). Here we examine GRIA2 expression in SFTs and other soft tissue tumours to evaluate its diagnostic utility. Immunohistochemistry was performed on 375 soft tissue tumours. In total, 84 of 105 (80%) SFTs, including 86% of malignant SFTs and 100% of dedifferentiated SFTs, were positive for GRIA2. One SFT known to harbor NAB2-STAT6 fusion but negative for STAT6 by immunohistochemistry was positive for GRIA2. Of note, 93% of SFTs received in the last 3 years were positive for GRIA2, compared to only 70% of older cases. The only other tumours that expressed GRIA2 were 15 of 20 (75%) cases of dermatofibrosarcoma protuberans (DFSP), 4 of 9 (44%) myoepitheliomas, 1 synovial sarcoma (<1% of cells), and 1 schwannoma. GRIA2 is a useful marker to distinguish SFT from most mimics. Among other CD34-positive tumours, GRIA2 is also expressed in DFSP; however, clinical and histologic features aid in their distinction. GRIA2 shows a limited distribution in other soft tissue tumours. This article is protected by copyright. All rights reserved.
    Histopathology 01/2014; 65(1). DOI:10.1111/his.12377 · 3.30 Impact Factor
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    ABSTRACT: Diagnosing anal squamous cell carcinoma (SCC), which is often preceded by anal intraepithelial neoplasia (AIN), may be challenging in small biopsies. Cytokeratin 17 (CK17) is a basal/myoepithelial cell keratin induced in activated keratinocytes and associated with disease progression in SCC of the uterine cervix, esophagus, and oral cavity. We investigated the utility of CK17 in diagnosing invasion in anal squamous neoplastic lesions. Immunohistochemical staining for CK17 was evaluated in 11 AINs, 12 invasive SCCs, 8 invasive SCCs with basaloid features (BSCC), and 2 invasive pure basaloid carcinomas. The pattern of staining was scored as surface/central, peripheral/rim, diffuse, or absent. All cases of invasive SCC and BSCC stained positive for CK17. Eleven of 12 (92%) SCCs showed diffuse staining, and 1 of 12 (8%) showed peripheral staining. Six of 8 (75%) BSCCs showed diffuse staining, and 2 of 8 (25%) showed peripheral staining. Both pure basaloid carcinomas were negative for CK17. One of 11 (9%) AINs was diffusely positive for CK17; all other AINs had surface or absent CK17. Of the 6 patients with concurrent AIN and invasive carcinoma, superficial expression of CK17 was present in 1 AIN, whereas all invasive components showed diffuse staining. The sensitivity and specificity of CK17 for identifying invasion in SCC and BSCC was 100% and 91%, respectively. Peripheral or diffuse staining for CK17 is a useful marker of invasion in anal squamous neoplastic lesions. A potential pitfall in the utility of CK17 is that the pure basaloid variant of anal carcinoma is negative for CK17.
    The American journal of surgical pathology 01/2014; 38(1):78-85. DOI:10.1097/PAS.0000000000000111 · 4.59 Impact Factor
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    ABSTRACT: Background. Due to concern that mucinous malignant or borderline ovarian neoplasms (MON) may represent metastatic deposits from appendiceal primaries, gynecologic oncologists routinely perform appendectomy in these cases. However, a multidisciplinary critique of this practice is lacking. Methods. The New England Case-Control study database was utilized to compare the effect of prior appendectomy against known risk factors for MON. Pathology and operative reports of local cases of MON were reviewed to estimate the frequency of microscopic mucinous lesions in the appendix. Protein expression patterns among mucinous ovarian, colorectal, and appendiceal cancers were compared by immunohistochemistry. Results. From the New England Case-Control study, 287 cases of MON were compared against 2339 age-matched controls. Prior appendectomy did not reduce the risk of MON (OR 1.28, 95% CI 0.83-1.92, p = 0.23), while prior tubal ligation, parity, and breastfeeding were each protective against MON. Active smoking (OR 2.04, 95% CI 1.48-2.80, p < 0.001) was associated with an increased risk of MON. Among 196 mucinous adnexal tumors, appendectomy did not reclassify any MON as appendiceal in origin. By immunohistochemistry, mucinous ovarian carcinomas tended to be CK7+/CK20-/MUC2-/CDX2-, whereas mucinous colorectal and appendiceal adenocarcinomas were typically CK7-/CK20+/MUC2+/CDX2+, although with some overlap in immunophenotype. Additionally, PAX8 was positive in a subset of MOC and negative in all appendiceal carcinomas. Conclusion. Prior appendectomy is not protective against development of malignant or borderline MON. Routine appendectomy during surgery for MON seldom reveals an unsuspected GI primary in early stage tumors but may aid in final diagnosis in advanced stage cases.
    Gynecologic Oncology 12/2013; 132(2). DOI:10.1016/j.ygyno.2013.12.011 · 3.69 Impact Factor
  • Leona A Doyle, Christopher D M Fletcher
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    ABSTRACT: Hemangioblastoma is a rare tumor of uncertain histotype that typically arises in the cerebellum, quite often in the setting of Von Hippel-Lindau syndrome (VHL). Exceptional cases of hemangioblastoma arising outside the central nervous system have been reported, but little is known about their clinicopathologic and immunohistochemical features. Twenty-two cases of hemangioblastoma arising at peripheral sites were identified in consultation files. Clinical, morphologic, and immunohistochemical features were evaluated. Outcome data were obtained from referring pathologists. Twelve patients were female and 10 male; the median age was 58 years (range, 27 to 79 y). All the tumors were solitary (except 1) and arose in spinal nerve roots (12), kidney (3), intestine (2), orbit (1), forearm (1), peritoneum (1), periadrenal soft tissue (1), and flank (1). Five patients had VHL; another 5 had lesions suggestive of VHL. One patient had tuberous sclerosis. The median tumor size was 4 cm (range, 1.3 to 15 cm). Most tumors were well circumscribed; 6 were poorly marginated-3 eroded the adjacent bone and 1 extended into the pleura. All tumors were composed of an admixed population of plump spindle cells and microvacuolated cells with palely eosinophilic or clear cytoplasm, which often mimicked lipoblasts or renal cell carcinoma. In 5 cases the microvacuolated cells were scant. Spindle cell nuclei were hyperchromatic or vesicular with inconspicuous nucleoli. Four tumors showed marked nuclear pleomorphism. Mitotic activity was low (range, 0 to 2/10 HPF). All tumors had a complex capillary network, with admixed larger thin-walled or thick-walled vessels in a solid and often lobular growth pattern, similar to central nervous system hemangioblastoma. In 9 cases the larger vessels showed a branching hemangiopericytoma-like pattern. No necrosis or lymphovascular invasion was identified. Tumor cells expressed inhibin in 95% (20/21), neuron-specific enolase in 79% (15/19), and S100 protein in 65% (13/20); they also expressed GLUT1 (7/10, mostly weak), SMA (4/5), epithelial membrane antigen (2/8, focal), PAX8 (1/10), and desmin (1/4). Brachyury was consistently negative (0/19), as were keratin, HMB-45, melan-A, and GFAP. CD31 and CD34 highlighted tumor vasculature. Follow-up information was available for 17 patients (range, 5 to 117 mo; median 36 mo). Three patients had locally persistent disease after incomplete resection. True local recurrence or distant metastasis has not been identified in any patient so far. One patient died of metastatic renal cell carcinoma. Peripheral hemangioblastoma is rare, often associated with VHL syndrome, and may mimic some malignant tumors. The immunohistochemical profile can aid diagnosis. Unresectable cases may be locally aggressive, but complete excision appears to be curative. Recognition of this tumor may identify patients in whom testing for VHL syndrome is warranted.
    The American journal of surgical pathology 10/2013; DOI:10.1097/PAS.0b013e3182a266c1 · 4.59 Impact Factor
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    Leona A Doyle, Jason L Hornick
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    ABSTRACT: The discovery of activating mutations in the tyrosine kinase receptor genes KIT and PDGFRA has led to the development of effective targeted therapies for gastrointestinal stromal tumors (GISTs). Specific genotypes in part predict response to treatment with tyrosine kinase inhibitors. However, approximately 10% of GISTs lack such mutations (often referred to as "wild-type" GISTs). Recent insights into the biology of "wild-type" GISTs have resulted in clinically significant sub-classification of this heterogeneous group of tumors, the majority of which are now known to represent succinate dehydrogenase-deficient GISTs. Recognition of this distinctive class of tumors has critical implications for prognosis, therapy, clinical follow-up, and genetic counseling. Other uncommon genetic groups include neurofibromatosis type I-associated and BRAF-mutant GISTs. This review will provide an update on the diagnosis and pathogenesis of these less common classes of GISTs, as well as summarize clinical and pathologic features associated with particular genotypes, and discuss mechanisms of resistance to targeted therapies. This article is protected by copyright. All rights reserved.
    Histopathology 10/2013; DOI:10.1111/his.12302 · 3.30 Impact Factor
  • Leona A Doyle, Jason L Hornick
    The American journal of surgical pathology 10/2013; 37(10):1630-1. DOI:10.1097/PAS.0b013e3182a05a6b · 4.59 Impact Factor
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    ABSTRACT: Perivascular epithelioid cell tumors (PEComas) are distinctive mesenchymal neoplasms that most often arise in the retroperitoneum, visceral organs, and abdominopelvic sites and usually show reactivity for melanocytic and smooth muscle markers. Fewer than 20 PEComas of the gastrointestinal (GI) tract have been reported, and behavior and criteria for malignancy are incompletely defined. The purpose of this study was to examine the clinicopathologic features of a series of GI PEComas and to evaluate prognostic parameters. A total of 35 PEComas of the GI tract were retrieved from consult and surgical files. Clinical and pathologic features were evaluated, and immunohistochemical analysis was performed. Clinical follow-up information was obtained from medical records and referring physicians. Nineteen patients were female and 16 male (median age 45 y; range, 7 to 70 y). One patient had tuberous sclerosis. Nineteen tumors arose in the colon, 12 in the small bowel, 2 in the stomach, and 1 each in gallbladder and omentum. Median tumor size was 6.2 cm (range, 0.8 to 22 cm). Three tumors were limited to the mucosa and submucosa, 8 extended to the muscularis propria, 15 to the subserosa/serosa, and 8 into the mesentery. The tumors were composed of nests and sheets of usually epithelioid cells with abundant granular eosinophilic to clear cytoplasm, surrounded by a delicate capillary vasculature. Thirteen tumors had mixed epithelioid and spindle cell components, and 2 were purely spindled. Sixteen tumors showed marked nuclear atypia. Seventeen tumors contained occasional pleomorphic cells, and 12 showed diffuse cellular pleomorphism. The median mitotic rate was 2/10 HPF (range, 0 to 36). Vascular invasion was present in 5 cases, and 16 tumors showed necrosis. By immunohistochemistry, 23/35 were positive for HMB45, 23/34 for melan-A, 15/25 for MiTF, 20/35 for smooth muscle actin, 26/35 for desmin, and 3/20 for TFE3. Focal cytoplasmic S100 protein was present in 5/27 cases, 2/25 cases were positive for KIT, and 1 case each was positive for EMA and keratin. Follow-up information was available for 31 patients (median 36 mo; range, 2 to 176 mo). Thirteen patients have developed metastases (10 liver, 3 peritoneum, 4 lymph node, 3 lung, 1 bone, 1 brain, and 1 adrenal). Thus far, 5 patients have died of disease. Metastases were significantly associated with marked atypia, diffuse pleomorphism, and mitoses ≥2/10 HPF. In summary, PEComas of the GI tract occur at similar frequency in female and male patients, most commonly involve the colon, and exhibit variable clinical behavior, ranging from benign lesions to aggressive, high-grade sarcomas. The presence of marked nuclear atypia, diffuse pleomorphism, and mitotic activity are the strongest predictors of malignant behavior.
    The American journal of surgical pathology 09/2013; DOI:10.1097/PAS.0b013e31829caab3 · 4.59 Impact Factor
  • Leona A Doyle, Christopher D M Fletcher
    Annals of Surgical Oncology 09/2013; 20(13). DOI:10.1245/s10434-013-3243-8 · 3.94 Impact Factor
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    ABSTRACT: Solitary fibrous tumor (SFT) is composed of spindled to ovoid cells in a patternless architecture with prominent stromal collagen and hemangiopericytoma-like vessels. Some tumors show hypercellularity, nuclear atypia, and significant mitotic activity; the latter feature in particular often portends an aggressive clinical course. SFT can sometimes be difficult to distinguish from other benign mesenchymal tumors and sarcomas. The most characteristic (albeit nonspecific) immunohistochemical finding in SFT is CD34 expression. A NAB2-STAT6 gene fusion, resulting in a chimeric protein in which a repressor domain of NGFI-A binding protein 2 (EGR1 binding protein 2) (NAB2) is replaced with a carboxy-terminal transactivation domain from signal transducer and activator of transcription 6, interleukin-4 induced (STAT6), was recently identified as a consistent finding in SFT. However, as these genes are located in close proximity on 12q13, this fusion can only rarely be detected by conventional chromosomal banding or fluorescence in situ hybridization analysis. Nuclear expression of the carboxy terminal part of STAT6 is a consistent finding in SFT of the meninges (so-called 'meningeal hemangiopericytoma'). We investigated STAT6 expression by immunohistochemistry in SFTs and other soft tissue tumors arising outside the central nervous system to validate the diagnostic utility of this novel marker. Whole-tissue sections of 231 tumors were evaluated, including 60 cases of SFT as well as other benign and malignant mesenchymal neoplasms and sarcomatoid mesotheliomas. Fifty-nine of 60 SFT cases (98%) showed nuclear expression of STAT6, which was usually diffuse and intense. All other tumor types were negative for STAT6, except for three dedifferentiated liposarcomas and one deep fibrous histiocytoma, which showed weak staining. In conclusion, STAT6 is a highly sensitive and almost perfectly specific immunohistochemical marker for SFT and can be helpful to distinguish this tumor type from histologic mimics.Modern Pathology advance online publication, 13 September 2013; doi:10.1038/modpathol.2013.164.
    Modern Pathology 09/2013; DOI:10.1038/modpathol.2013.164 · 6.36 Impact Factor
  • Leona A. Doyle, Jason L. Hornick
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    ABSTRACT: Mesenchymal tumors involve the gastrointestinal (GI) tract more frequently than other visceral organs. Many such tumors are small, and are benign and increasingly being detected incidentally during colonoscopic screening. Some tumors show distinctive features at this site, such as schwannoma and clear cell sarcoma–like tumor of the GI tract. Without knowledge of these features, recognition of these tumor types can be difficult. This reviews addresses recent developments and diagnostic features of mesenchymal tumors of the GI tract other than gastrointestinal stromal tumor (GIST).
    Surgical Pathology Clinics 09/2013; 6(3):425–473. DOI:10.1016/j.path.2013.05.003
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    ABSTRACT: Patients with inflammatory bowel disease (IBD) may develop a variety of neoplastic and nonneoplastic polyps. This review covers the pathology, pathogenesis, natural history, and treatment of polyps in IBD with special emphasis on dysplastic lesions. Elevated or polypoid dysplastic lesions in IBD patients are referred to by the acronym DALM (dyspasia-associated lesion or mass). DALMs are further categorized as adenoma-like (endoscopically resectable polypoid dysplasia) or non–adenoma-like (non–endoscopically resectable polypoid dysplasia) based on their endoscopic appearance. Colectomy is recommended for patients with a non–adenoma-like DALM because of the high risk of synchronous or metachronous adenocarcinoma. In contrast, adenoma-like DALMs can be safely treated by polypectomy and continued surveillance provided that the lesion is removed in total, with negative margins, and no flat dysplasia is identified in the colon adjacent to and distant from the polyp.
    Techniques in Gastrointestinal Endoscopy 04/2013; 15(2):113–120. DOI:10.1016/j.tgie.2013.02.002