John F Fetsch

National Cancer Institute (USA), Maryland, United States

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Publications (57)207.29 Total impact

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    ABSTRACT: Intranodal palisaded myofibroblastoma is a benign, lymph node-based myofibroblastic tumor of unknown pathogenesis. We report the clinicopathologic, immunohistochemical, and molecular genetic features of this rare entity. The study cohort consisted of 14 men and 4 women ranging in age from 31 to 65 (mean, 47; median 49) years with tumors arising in inguinal lymph nodes (n=15), a neck lymph node (n=1), and undesignated lymph nodes (n=2). Most individuals presented with a painless mass or lump. Possible trauma/injury to the inguinal region was documented in 4 cases. Tumors ranged in size from 1.0 to 4.2 (mean, 3.1; median; 3.0) cm. Microscopically, the process presented as a well-circumscribed, oftentimes pseudoencapsulated nodule (n=17) or nodules (n=1). Tumors consisted of a cellular proliferation of cytologically bland, spindled cells arranged in short fascicles and whorls within a finely collagenous (n=11) or myxocollagenous (n=7) matrix. In 12 tumors, scattered fibromatosis-like fascicles of spindled cells were noted. Histologic features characteristic of the process included nuclear palisades (n=16 cases), collagenous bodies (n=15), and perinuclear intracytoplasmic hyaline globules (n=10). Mitotic activity ranged from 0 to 8 (mean, 2; median, 1) mitotic figures/50 high-powered fields with no atypical division figures identified. Immunohistochemically, all tumors tested expressed smooth muscle actin and/or muscle-specific actin (n=5, each), and nuclear β-catenin and cyclin D1 (n=8, each). The latter 2 results prompted a screening for mutations in the β-catenin gene glycogen synthase kinase-3 β phosphorylation mutational "hotspot" region in exon 3 using polymerase chain reaction amplification and Sanger sequencing. Single nucleotide substitutions leading to missense mutations at the protein level were identified in 7 of 8 (88%) analyzed tumors and are responsible for the abnormal expression of β-catenin and cyclin D1. These results demonstrate that mutational activation of the β-catenin gene is likely a pivotal event in the pathogenesis of intranodal palisaded myofibroblastoma.
    The American journal of surgical pathology. 07/2014;
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    ABSTRACT: In this study, we examine the clinicopathologic features of 104 cases of myxoinflammatory fibroblastic sarcoma (MIFS), a low-grade, inflammatory fibromyxoid tumor with a predilection to distal extremity soft tissue, and attempt to identify factors predictive of aggressive behavior. The study cohort consisted of 49 male and 55 female patients ranging in age from 17 to 83 (mean, 42; median, 39) years. The tumor arose primarily on the dorsal aspect of the distal extremities as a solitary and usually painless mass. Tumors ranged in size from 0.5 to 15 (mean, 3.2; median; 2.4) cm. Microscopically, tumors consisted of variably cellular and inflamed fibromyxoid tissue growing as a lobulated mass or as multiple nodules within subcutaneous tissue or along tendinofascial planes. Tumor cells ranged from plump spindled to more epithelioid cells with enlarged, vesicular nuclei. Characteristic of the process was a strikingly bizarre cell with an inclusion body-like nucleolus (85% of cases) and/or a smudgy hyperchromatic nucleus (51%) present in all but 7 cases. The mitotic rate per 50 high-power field ranged from 0 to 13 (mean, 2,9; median, 2) mitoses. Twenty-two tumors demonstrated 1 or more of the following atypical features: (1) foci with complex sarcoma-like vasculature; (2) hypercellular areas; and (3) increased mitotic activity or atypical mitotic figures. Immunohistochemically, tumor cells demonstrated immunoreactivity for vimentin (100%), D2-40 (86%), CD34 (50%), keratin(s) (33%), CD68 (27%), actin(s) (26%), desmin (9%), S-100 protein (7%), and epithelial membrane antigen (6%). Thirty of 59 patients (51%) with follow-up data suffered (at least) 1 local recurrence, and 1 patient developed metastatic disease after multiple local recurrences. Completeness of initial surgical excision was the only clinicopathologic parameter that statistically correlated with a lower incidence of recurrence (P=0.004). Histologically atypical MIFS recurred more often than conventional tumors (67% vs. 47%), but the difference was not statistically significant (P=0.35). Our study shows that histologic features often associated with more aggressive sarcomas do not substantially impact the morbidity of MIFS, and complete surgical excision provides the best chance for disease-free survival.
    The American journal of surgical pathology 10/2013; · 4.59 Impact Factor
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    ABSTRACT: ERG transcription factor is constitutively expressed in endothelial cells. Because benign and malignant vascular endothelia retain the ERG expression, ERG is considered a useful marker for angiosarcomas and related tumors. ERG is also expressed in a subset of prostate carcinomas and Ewing sarcomas due to ERG-involved translocations; therefore, this marker is also of high interest in the study of these malignancies. In this study, we evaluated 109 epithelioid sarcomas for ERG expression, on the basis of an initial observation of an ERG-positive case. We also studied expression of other endothelial antigens in epithelioid sarcoma. ERG was expressed in 38% of epithelioid sarcomas (41/109), usually with a uniform nuclear staining, similar to that seen in angiosarcomas. However, all epithelioid sarcomas were negative for ERG gene rearrangement indicating that ERG expression is not likely related to ERG-involving translocations in epithelioid sarcoma. Other endothelial markers, CD31, claudin 5, and Prox1, were absent in epithelioid sarcomas. The only exception was a pulmonary metastasis of epithelioid sarcoma showing focal CD31 expression, which probably resulted from antigen adsorption onto tumor cell surfaces. However, podoplanin was commonly (7/9) expressed in epithelioid sarcoma; therefore, this marker is not useful in distinguishing epithelioid sarcoma from angiosarcoma. INI1/SMARCB1 gene product was absent in all epithelioid sarcomas (considered here a definitional feature) but was absent from only 1 epithelioid angiosarcoma, indicating its relative specificity for epithelioid sarcoma in this differential diagnostic setting. ERG expression is fairly common in epithelioid sarcoma and should be recognized as a diagnostic pitfall in the differential diagnosis of epithelioid sarcoma and epithelioid angiosarcoma. General lack of endothelial cell-specific markers in epithelioid sarcoma helps in this distinction.
    The American journal of surgical pathology 06/2013; · 4.59 Impact Factor
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    Eric A Walker, Mark D Murphey, John F Fetsch
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    ABSTRACT: Our purpose was to identify imaging characteristics of tenosynovial and bursal chondromatosis. We retrospectively reviewed 25 pathologically confirmed cases of tenosynovial (n = 21) or bursal chondromatosis (n = 4). Patient demographics and clinical presentation were reviewed. Imaging was evaluated by two musculoskeletal radiologists with agreement by consensus, including radiography (n = 21), bone scintigraphy (n = 1), angiography (n = 1), ultrasonography (n = 1), CT (n = 8), and MR (n = 8). Imaging was evaluated for lesion location/shape, presence/number of calcifications, evidence of bone involvement, and intrinsic characteristics on ultrasonography/CT/MR. Average patient age was 44 years (range 7 to 75 years) with a mild male predilection (56%). A slowly increasing soft tissue mass was the most common clinical presentation (53%). Lesion locations included the foot (n = 8), hand (n = 6), shoulder (n = 3), knee (n = 2), ankle (n = 2) and one each in the upper arm, forearm, wrist, and cervical spine. All lesions were located in a known tenosynovial (21 cases, 84%) or bursal (four cases, 16%) location. All cases of bursal chondromatosis were round/oval in shape. Tenosynovial lesions were fusiform (65%) or round/oval (35%). Radiographs commonly showed a soft tissue mass (86%) and calcification (90%). Calcifications were predominantly chondroid (79%) or osteoid (11%) in character with >10 calcified bodies in 48%. CT detected calcifications in all cases. The intrinsic characteristics of the nonmineralized component showed low attenuation on CT (75%), high signal intensity on T2-weighted MR (76%) and a peripheral/septal contrast enhancement pattern (100%). Imaging of tenosynovial and bursal chondromatosis is often characteristic with identification of multiple osteochondral calcifications (90% by radiographs; 100% by CT). CT and MR also revealed typical intrinsic characteristics of chondroid tissue and lesion location in a known tendon sheath or bursa.
    Skeletal Radiology 03/2011; 40(3):317-25. · 1.74 Impact Factor
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    ABSTRACT: Assessment of the biological potential of smooth muscle tumors can be difficult and depends primarily on tumor site, stage, and histologic parameters. In this study, we examined the clinicopathologic and immunohistochemical features of 55 noncutaneous inguinal smooth muscle tumors of women (age range, 20 to 82 y; median, 57 y). Histologically, 23 tumors were considered as leiomyomas. They showed low mitotic activity (range, 0 to 6 mitoses/10 high-power fields, without atypical mitotic figures), minimal cytologic atypia, and absence of coagulative necrosis. Fifteen of these tumors histologically resembled conventional uterine leiomyomas and 8 resembled their variants: lipoleiomyomas (n = 2) and epithelioid variants (n = 6). The mean size was 7.8 cm, and half of the tumors with specified location arose in association with the round ligament. Immunohistochemical expression of estrogen receptor (ER) and/or Wilms tumor protein (WT1) was detected in most cases (83%), supporting Müllerian derivation. Follow-up data (range, 10 to 29 y; median, 13 y) on 11 patients showed that all were alive without disease or death from unrelated causes. The second group, classified as leiomyosarcomas, consisted of 32 mitotically active smooth muscle tumors, almost invariably with atypical mitotic figures, and exhibiting significant cytologic atypia. These patients were older than those with leiomyomas, and their tumors were mostly subcutaneous with a mean tumor size of 5.4 cm. Two leiomyosarcomas showed a femoral vein origin, but none were associated with the round ligament. All but 3 leiomyosarcomas were negative for ER. Follow-up data on 13 patients (range, 2 mo to 30 y; median, 4.5 y) showed that 5 died of metastatic sarcoma. Six individuals were alive without disease (median, 16 y), and 2 died of unrelated causes. In conclusion, inguinal smooth muscle tumors in women are a dichotomous group. They consist of ER/WT1-positive Müllerian-type leiomyomas resembling uterine leiomyomas with an excellent prognosis and conventional LMSs that are usually ER/WT1-negative and show a variable malignant course. Separation of these 2 categories is important for prognostication and optimal patient management, and is aided by immunohistochemical studies for ER and WT1.
    The American journal of surgical pathology 03/2011; 35(3):315-24. · 4.59 Impact Factor
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    ABSTRACT: This report details the clinicopathologic features and follow-up data on 40 cases of inferior vena cava leiomyosarcoma, a rare sarcoma with a poor prognosis. Study cohort consisted of 31 females and 9 males (mean age, 53 y), whose material was accessioned to the Armed Forces Institute of Pathology between 1976 and 2008. Inferior vena cava leiomyosarcomas ranged in size from 3.5 to 15.0 (median, 8.5) cms, and most involved the middle segment of the vessel and grew extraluminally. Eleven leiomyosarcomas were French Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) histologic grade I; 21, grade II; and 5 were grade III. Eleven of 33 patients managed by complete or radical resection had involved surgical margins. Twenty of the 34 patients (59%) with clinical follow-up data (mean, 33.5; median, 51 mo) died of sarcoma-related complications and 9 (26%) of unknown causes. The 5-year and 10-year survival rates after resection without documented residual macroscopic disease were 50% and 22%, respectively. Two patients are alive without disease 9 and 18 years after last surgical intervention. Suprahepatic vena caval and right atrial involvement by tumor, predominant intraluminal tumor growth, and residual postsurgical macroscopic disease were factors that statistically correlate with death within 2 years. By univariate analysis, intraluminal tumor (P=0.03), liver injury or failure (compromised liver) (P=0.01), and moderate to poor tumor differentiation (P=0.03) were associated with increased tumor-related mortality, whereas a compromised liver (P=0.01) was the only factor correlated with mortality by multivariate analysis. Our study concludes that a macroscopic resection of localized inferior vena cava leiomyosarcoma provides the best chance for long-term survival, suprahepatic tumors often result in early death, and a compromised liver correlates with overall poor survival, but French Federation Nationale des Centres de Lutte Contre le Cancer grading does not affect prognosis.
    The American journal of surgical pathology 06/2010; 34(6):873-81. · 4.59 Impact Factor
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    ABSTRACT: Perivascular epithelioid cell tumors comprise a rare and recently described family of neoplasms that characteristically coexpress melanocytic and myoid markers. We describe the clinicopathologic features of 2 ocular cases. Case 1 occurred in a 26-year-old woman with a recurrent left upper eyelid tumor, and case 2 was diagnosed in a 7-year-old boy with a left ciliary body mass. This is the first report of perivascular epithelioid cell tumor arising in the ciliary body or eyelid. Neither patient in our series had documented evidence of the tuberous sclerosis complex. Despite its rarity, perivascular epithelioid cell tumor should be considered in the differential diagnosis of ocular melanocytic lesions. Although most examples appear cytologically bland, experience is limited regarding their malignant potential; and therefore, complete surgical resection and close follow-up are recommended.
    Human pathology 03/2010; 41(5):768-72. · 2.81 Impact Factor
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    ABSTRACT: The clinicopathologic and immunohistochemical features of 69 pediatric examples of infantile digital fibroma/fibromatosis (IDF) were analyzed. Thirty males, 26 females, and 1 child (sex unstated) ranging from newborn to 120 months of age (median, 12 mo) manifested 74 lesions (5 identified in follow-up) involving the toe or finger (n=71) and the hand or foot (n=3). Tumors ranged in size from 3 to 35 (median, 10) mm. All but 4 study members presented with a solitary lesion. Metachronous IDFs developed in 7 patients within 17 to 82 months. Microscopically, a cytologically bland, fibroproliferative lesion was observed forming a dome-shaped/polypoid nodule directly beneath the epidermis and invading dermal adnexa. Mitotic figures per 20 high-powered fields ranged from 0 to 7 (median, 1). Paranuclear cytoplasmic inclusions were identified in 57 tumors. Tumor cells immunohistochemically expressed calponin (11 of 11 tumors), desmin (9/9), alpha-smooth muscle actin (11/11), CD99 (11/11), CD117 (6/8), heavy caldesmon (2/11 and scattered cytoplasmic inclusions in 4 tumors), CD10 (1/9), nuclear beta-catenin (2/11), and CD34 (1/11), but not muscle actin (HUC1-1), keratins, estrogen/progesterone receptor proteins, or activated caspase-3. Twenty-eight of 38 patients (74%) experienced recurrent/persistent disease (single in 22; multiple in 6) (median, 4 mo after surgery). One recurrent tumor spontaneously regressed and the size of another remained unchanged for almost 17 years before reexcision. All 23 patients with >5 years follow-up are currently disease free (median disease-free interval, 23 y). Minor postoperative functional/cosmetic complaints were reported in 47%. No patient with adequate clinical data developed the digitocutaneous dysplasia syndrome or a conventional fibromatosis, or relayed a family history of IDF/conventional fibromatosis. Our results indicate that IDF is a unique myofibroblastic process separable from conventional fibromatoses and from histologic mimics. Conservative excision or observation after biopsy (with additional surgery employed as necessary) are recommended treatment options.
    The American journal of surgical pathology 10/2008; 33(1):1-13. · 4.59 Impact Factor
  • Markku Miettinen, Val Finnell, John F Fetsch
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    ABSTRACT: Ossifying fibromyxoid tumor (OFT) is a unique soft tissue tumor of uncertain histogenesis. The majority of reported cases (approximately 220) have pursued a benign clinical course. However, recent literature has emphasized the existence of morphologically atypical and clinically malignant examples of this tumor and proposed guidelines for assessment of biologic potential. In the present study, we evaluated 104 cases of OFT from the Armed Forces Institute of Pathology, accessioned between the years 1970 and 2007. Herein, OFT was strictly defined as a tumor with lobular architecture, predominantly epithelioid cell morphology, a low level of atypia, corded and trabecular growth patterns, moderate amounts of myxocollagenous matrix, and often, focal peripheral metaplastic bone formation. Tumors that lacked conventional morphology were excluded. The exclusion group included cutaneous mixed tumors, low-grade fibromyxoid sarcomas, and extraskeletal osteosarcomas. The OFTs occurred in 64 men and 40 women with a median age of 50 years (range, 21 to 81 y). The tumor size ranged from 0.7 to 17 cm (median, 3 cm). The mitotic rate varied from 0 to 41 mitotic figures per 50 HPFs (median, 2/50 HPFs). Tumor cell nuclei typically contained small, distinct nucleoli, and necrosis was infrequent (11/104). The great majority of tumors (67/71, 94%) were positive for S100 protein, whereas only occasional examples had (focal) positivity for desmin, glial fibrillary acidic protein, and an AE1/AE3 keratin cocktail. Local recurrences were documented in 9 of 41(22%) living patients, usually 10 or more years after primary surgery, but there were no metastases. A mitotic rate of >2 mitotic figures/50 HPFs was a risk factor for local recurrence, but necrosis, tumor size, the presence of satellite nodules, and positive margins were not. When OFT is strictly defined by the criteria noted above, there is potential for local recurrence, but there seems to be little or no risk for metastasis.
    The American journal of surgical pathology 07/2008; 32(7):996-1005. · 4.59 Impact Factor
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    ABSTRACT: 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=10 years of age and only 20% 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.
    American Journal of Surgical Pathology 07/2007; 31(7):1103-14. · 4.59 Impact Factor
  • Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 04/2007; 103(4).
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    ABSTRACT: Tumors of the soft tissues and bones form a heterogeneous group that includes common benign neoplasms as well as other less common, variably malignant neoplasms (sarcomas). Recent advances in molecular and cell biology have influenced considerably the present clinical approach to these tumors. As the classifications of these tumors, most notably that of soft tissue sarcomas, are constantly refined by the addition of new data, the grading of soft tissue and bone sarcomas remains a work in progress (1, 2). Accordingly, only the most established grading systems used in daily surgical pathology practice are presented here.
    03/2007: pages 91-98;
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    ABSTRACT: 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.
    American Journal of Surgical Pathology 02/2007; 31(1):15-25. · 4.59 Impact Factor
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    ABSTRACT: This report details the clinicopathologic and immunohistochemical findings identified in 21 cases of a fibrosclerotic variant of lipoma from acral sites that is frequently misdiagnosed as a fibromatous (nonlipogenic) process. The study includes 12 males and 9 females; aged 7 to 72 (mean and median, 39). The patients presented with solitary, mostly asymptomatic, masses that ranged from 0.6 to 2.2 (median, 1.2; mean, 1.3) cm and involved fingers (n=17), hands or wrists (n=3), and toes (n=1). Microscopically, the lesions were well-circumscribed nodules that showed very low to moderately low cellularity and consisted of cytologically bland spindled and stellate-shaped cells and a minor component of randomly dispersed adipocytes embedded in a collagenous to myxocollagenous stroma. Eight tumors were "fibroma-like" owing to their paucity of spindled cells, dense fibrosclerotic stroma, and inconspicuous vasculature. One tumor showed features of spindle cell/pleomorphic lipoma, whereas another demonstrated a vague onion skin-like arrangement of collagen reminiscent of sclerotic (storiform) fibroma. In all cases, the mitotic activity was negligible. Nonlipogenic tumor cells were immunoreactive for CD99 (6 of 6 cases), CD34 (6 of 8), S-100 protein (4 of 7), and smooth muscle actin (2 of 6). Follow-up data on 8 patients (range, 1 to 20 years; median, 9.5 years) revealed no recurrence in 6, but indicated the possibility of persistent tumor in the remaining 2 individuals after simple excision. Despite histological overlap in 1 case with the sclerotic fibroma, no patient displayed definitive clinical features of Cowden syndrome. Our study indicates that fibrosclerotic lipomas demonstrate a broader histological scope than what was initially described.
    American Journal of Dermatopathology 09/2006; 28(4):308-16. · 1.43 Impact Factor
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    ABSTRACT: Synovial sarcoma, one of the most common types of soft tissue sarcomas, usually presents in the proximal or middle portions of the extremities, often as a large mass with an aggressive clinical behavior. Gland-forming biphasic and spindle cell fibrous monophasic tumors are the most common subtypes. In this study, we evaluated 21 minute synovial sarcomas, <1 cm in diameter, from the hands and feet. These tumors occurred in 14 females and 7 males with a median age of 29 years (range, 8-60 years). Clinically, all tumors were thought to be benign processes such as a ganglion cyst or glomus tumor, and on microscopic examination, they were also often initially misinterpreted as benign lesions such as nerve sheath or (myo) fibroblastic tumors. Histologically, 7 tumors were biphasic and 14 were monophasic spindle cell variants. Microscopic calcifications were present in 8 cases and were prominent in 3 tumors. All monophasic tumors tested had elements positive for EMA, and all but one had reactivity for a keratin cocktail. S-100 protein-positive neuroma-like neural proliferations were commonly present in the monophasic but not in biphasic tumors. SYT-SSX fusion transcripts were demonstrated in 5 cases studied by polymerase chain reaction assay. All tumors were enucleated, followed by local reexcision of the site, and often combined with postoperative radiation. Three patients had amputation of the involved digit or metatarsal. Four patients had local recurrences, 2 of which were successfully treated; 2 of these patients were lost to follow-up. Despite some variation in treatment, all 12 patients with complete follow-up were alive and well, 2 to 32.2 years after surgery (median, 14.7 years), including 2 patients who received neither amputation nor postoperative radiation. Minute synovial sarcomas of hands and feet are clinically favorable tumors if completely excised; there is some evidence to suggest that they may be managed more conservatively than larger tumors. These tumors should be recognized as part of the spectrum of synovial sarcomas.
    American Journal of Surgical Pathology 06/2006; 30(6):721-6. · 4.59 Impact Factor
  • Markku Miettinen, John F Fetsch
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    ABSTRACT: Reticulohistiocytoma and multicentric reticulohistiocytosis are designations for uncommon, incompletely characterized histiocytic proliferations of the skin or soft tissues. In this study, we analyzed a uniform group of 44 lesions composed of epithelioid histiocytes, comprising a subset of lesions originally designated as reticulohistiocytoma, and propose designating them as "solitary epithelioid histiocytoma" (SEH), in line with the recently published classification proposal for histiocytic disorders. There were 26 males and 18 females with a median age of 35 years (range, 2.5-74 years). All patients had a superficial, circumscribed, mildly elevated, solitary lesion (size range, 1.5-11 mm; median, 4 mm), located in the trunk wall (n = 16), lower extremity (n = 12), head and neck (n = 8, including 2 in the oral cavity), upper extremity (n = 6), penis (n = 1), and an unspecified site (n = 1). Histologically, the lesions typically involved upper and mid-dermis and were not ulcerated. They were composed of large epithelioid histiocytes with a varying number of lymphocytes and neutrophils. The histiocytes had abundant, typically densely eosinophilic, cytoplasm and mostly mild, if any, nuclear atypia. Multinucleated forms with randomly oriented nuclei were also present. The histiocytes had low mitotic activity (range, 0-4 mitoses per 10 wide HPFs; median, 1 mitosis per 10 HPFs). The lesions contained varying numbers of CD3-positive T cells, whereas B lymphocytes, plasma cells, eosinophils, and mast cells were scant, if present at all. Immunohistochemically, the epithelioid histiocytes were positive for CD163, CD68, lysozyme (variably), and vimentin. They often had focal nuclear immunoreactivity for microphthalmia transcription factor, and they sometimes had focal reactivity for Factor XIIIa and S-100 protein. Membrane positivity for CD31, CD43, and CD45 was variable. The epithelioid histiocytes were consistently negative for CD3, CD20, CD30, HMB45, and keratins. All 12 patients with follow-up information had an uneventful clinical course with no recurrences (median, 13 years). SEH is a benign, probably reactive, histiocytic proliferation of unknown etiology. It needs to be distinguished from Rosai-Dorfman disease, juvenile xanthogranuloma, a variety of granulomatous conditions, and some malignant neoplasms, including histiocytic sarcoma, melanoma, and epithelioid sarcoma.
    American Journal of Surgical Pathology 05/2006; 30(4):521-8. · 4.59 Impact Factor
  • M Miettinen, J F Fetsch
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    ABSTRACT: Smooth muscle tumours (SMTs) have been traditionally divided into benign leiomyomas (LM) and malignant leiomyosarcomas (LMS) based on cytological atypia, mitotic activity and other criteria. In most instances, this dichotomous approach works, but in some instances the biological potential cannot be determined with certainty. This is often because some, but not all criteria for malignancy have been met or because the tumours are occurring in unusual settings for which there are sparse substantive data. Tumours falling into the latter categories are often designated as 'smooth muscle tumours of uncertain malignant potential'. For most non-hormonally influenced SMTs, the presence of significant atypia plus mitotic activity equates with a diagnosis of LMS. However, not all tumours classified as LMSs have a similar prognosis, as a number of other factors, including tumour size, depth, grade and resectability, affect outcome. For example, cutaneous SMTs, regardless of mitotic activity and atypia, have potential largely limited to local recurrence, whereas subcutaneous and deep LMSs have a definite metastatic potential. Angioleiomyoma is the most common SMT of peripheral soft tissues, but deep peripheral LMs are distinctly rare and should be approached with caution. Hormonally influenced oestrogen- and progesterone receptor-positive uterine and extrauterine SMTs in women have unique criteria, including the allowance of higher mitotic activity for the benign LM designation. SMTs of female genital tract can be assessed with criteria similar to uterine tumours. Because of the rarity of these tumours, experience is more limited, and more caution is needed to assess the potential of tumours with mitotic activity and atypia. This review summarizes the current knowledge, guidelines, prognostic data and controversies for the classification of SMTs of soft tissue and most visceral sites.
    Histopathology 02/2006; 48(1):97-105. · 3.30 Impact Factor
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    ABSTRACT: Gastrointestinal stromal tumors (GISTs), the specific KIT- or PDFGRA-signaling driven mesenchymal tumors, most commonly occur sporadically, but there seems to be some increased tendency for these tumors to develop in patients with neurofibromatosis 1 (NF1). The clinicopathologic profile, KIT, and PDGFRA mutation status and long-term prognosis of patients with GIST in NF1 are incompletely characterized. In this study, we analyzed 45 patients who had NF1 and GIST. There were 26 females and 19 males with a median age of 49 years (10 years lower than the median age of GIST patients in general). A great majority of tumors occurred in the jejunum or ileum, with multiple tumors occurring in 28 cases. Ten patients had a duodenal and one had a gastric GIST. The most common presentations were gastrointestinal bleeding and anemia, and many patients had intermittent bleeding over several years. The majority of the tumors were small and mitotically inactive; only 7 had mitotic activity >5/50 HPFs and 15 tumors were >5 cm. Associated Cajal cell hyperplasia was common. One patient had an intraabdominal peri-intestinal neurofibroma. Five of 35 patients with follow-up died of metastatic disease; all of these had a tumor >5 cm, mitotic rate >5/50 HPFs, or both; three of these tumors were located in the duodenum. The presence of multiple small tumors was not associated with progressive disease. Most patients with long-term follow-up enjoyed a good prognosis; 2 died of other NF1-associated tumors (malignant peripheral nerve sheath tumors, brain tumor). None of the 16 tumors from 15 patients had a KIT exon 9, 11, 13, or 17 or PDGFRA exon 12 or 18 mutation as is typically seen in sporadic GISTs, indicating that GISTs in NF1 patients have a different pathogenesis than sporadic GISTs.
    American Journal of Surgical Pathology 01/2006; 30(1):90-6. · 4.59 Impact Factor
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    ABSTRACT: 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.
    American Journal of Surgical Pathology 01/2006; 29(12):1615-24. · 4.59 Impact Factor
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    ABSTRACT: 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.
    American Journal of Surgical Pathology 09/2005; 29(8):1095-105. · 4.59 Impact Factor

Publication Stats

2k Citations
207.29 Total Impact Points


  • 2013
    • National Cancer Institute (USA)
      • Laboratory of Pathology
      Maryland, United States
  • 1997–2013
    • Northwestern University
      • Department of Pathology
      Evanston, Illinois, United States
  • 2011
    • Uniformed Services University of the Health Sciences
      Maryland, United States
  • 1993–2011
    • Armed Forces Institute of Pathology
      Ralalpindi, Punjab, Pakistan
  • 2005–2010
    • Northwestern Memorial Hospital
      Chicago, Illinois, United States
  • 1999
    • Faculty of Medicine in Pilsen
      Pilsen, Plzeňský, Czech Republic
  • 1990–1992
    • Mayo Foundation for Medical Education and Research
      • • Department of Diagnostic Radiology
      • • Department of Pathology
      Scottsdale, AZ, United States