National pilot of entrustable professional activities in pathology residency training.

Entrustable professional activities (EPAs) are observable clinical skills and/or procedures that have been introduced into medical education at the student and resident levels in most specialties to determine readiness to advance into residency or independent practice, respectively. This publication describes the process and outcomes of a pilot study looking at the feasibility of using two anatomic pathology and two clinical pathology EPAs in pathology residency in 6 pathology residency programs that volunteered for the study. Faculty development on EPAs and their assessment was provided to pilot program faculty, and EPA assessment tools were developed and used by the pilot programs. Pre- and post-study surveys were given to participating residents, faculty, and program directors to gauge baseline practices and to gather feedback on the EPA implementation experience. Results demonstrated overall good feasibility in implementing EPAs. Faculty acceptance of EPAs varied and was less than that of program directors. Residents reported a significant increase in the frequency with which faculty provided formative assessments that included specific examples of performance and specific ways to improve, as well as increased frequency with which faculty provided summative assessments that included specific ways to improve. EPAs offered the most benefit in setting clear expectations for performance of each task, for providing more specific feedback to residents, and in increasing Program director's understanding of resident strengths abilities and weaknesses.

Role of the nuclear receptor coactivator AIB1/SRC-3 in angiogenesis and wound healing.

The nuclear receptor coactivator amplified in breast cancer 1 (AIB1/SRC-3) has a well-defined role in steroid and growth factor signaling in cancer and normal epithelial cells. Less is known about its function in stromal cells, although AIB1/SRC-3 is up-regulated in tumor stroma and may, thus, contribute to tumor angiogenesis. Herein, we show that AIB1/SRC-3 depletion from cultured endothelial cells reduces their proliferation and motility in response to growth factors and prevents the formation of intact monolayers with tight junctions and of endothelial tubes. In AIB1/SRC-3(+/-) and (-/-) mice, the angiogenic responses to subcutaneous Matrigel implants was reduced by two-thirds, and exogenously added fibroblast growth factor (FGF) 2 did not overcome this deficiency. Furthermore, AIB1/SRC-3(+/-) and (-/-) mice showed similarly delayed healing of full-thickness excisional skin wounds, indicating that both alleles were required for proper tissue repair. Analysis of this defective wound healing showed reduced recruitment of inflammatory cells and macrophages, cytokine induction, and metalloprotease activity. Skin grafts from animals with different AIB1 genotypes and subsequent wounding of the grafts revealed that the defective healing was attributable to local factors and not to defective bone marrow responses. Indeed, wounds in AIB1(+/-) mice showed reduced expression of FGF10, FGFBP3, FGFR1, FGFR2b, and FGFR3, major local drivers of angiogenesis. We conclude that AIB1/SRC-3 modulates stromal cell responses via cross-talk with the FGF signaling pathway.

Enhancing the Pipeline of Pathologists in the United States.

The shortage of pathologists in the United States has been a topic of discussion for the past 2 decades. At the 2014 Association of Pathology Chairs (APC)/Program Directors Section (PRODS) meeting, a Pipeline Subcommittee (PSC) of the APC Advocacy Committee was formed with the charge of investigating ways to increase the number of highly qualified United States Medical Graduates entering into pathology. Several online surveys were developed to identify the strengths, weaknesses, opportunities, and threats to recruitment into pathology. Two general pipeline surveys were completed; one was issued in 2014 and is discussed in this article. In 2018, the Medical Education Working Group surveyed the Undergraduate Medical Education Directors Section on the state of undergraduate medical education for pathology; pipeline issues are included in this article from the 2018 survey. Medical schools that reported 2% to 5% or more of their graduates going into pathology were compared with schools where less than 1% went into pathology. About one-third of schools producing more pathology residents had Post-Sophomore Pathology Fellowships. Schools that had a faculty member on the curriculum committee that felt they had little or no control were more likely to have fewer graduates going into pathology. Schools having students view an autopsy as a requirement of graduation were more likely to produce graduates going into pathology. However, none of these characteristics achieved statistical significance. Continued incorporation of best practices for exposure of pathology as a medical specialty as well as outreach to students will be necessary for the future pipeline.

Identifying the Challenges of "Small" Pathology Residency Programs and Creating Collaborative Solutions.

The majority of pathology residency training programs in the United States are considered to be small training programs. Small training programs, regardless of specialty, encounter unique challenges that have been documented in the literature. With the implementation of the Next Accreditation System (NAS), and other Accreditation Council for Graduate Medical Education (ACGME) Common Program Requirements, adequate personnel and other resources are necessary. An online survey was conducted on the pathology program directors' section listserv to help identify characteristics and challenges of small pathology residency training programs. A discussion group on small pathology residency programs was held at the 2015 Association of Pathology Chairs/Program Directors annual meeting, where the results of the survey were discussed and small breakout groups followed the discussion of the survey. The results of the online survey and discussion groups are discussed in this paper.

Nuclear beta-catenin expression distinguishes deep fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions.

Deep fibromatoses (desmoid tumors) are clonal myofibroblastic proliferations that are prone to aggressive local recurrences but that do not metastasize. They must be distinguished from a host of fibroblastic and myofibroblastic lesions as well as from smooth muscle neoplasms. Virtually all deep fibromatoses have somatic beta-catenin or adenomatous polyposis coli (APC) gene mutations leading to intranuclear accumulation of beta-catenin. Since low-grade sarcomas in general lack beta-catenin and since reactive proliferations would not be expected to have it, we predicted that nuclear beta-catenin expression would be detected in deep fibromatoses but absent in other entities in the differential diagnosis. We evaluated the role of beta-catenin to help differentiate distinguish deep fibromatoses from congeners. Formalin-fixed, paraffin-embedded sections from 21 lesions from 20 patients with deep fibromatoses were stained with monoclonal beta-catenin antibody (Transduction Laboratories) and compared with low-grade fibromyxoid sarcoma (n=12), leiomyosarcoma (n=10), various other fibrosarcoma variants (n=13, including 3 myofibrosarcomas, 3 sclerosing epithelioid fibrosarcomas, 5 low-grade fibrosarcomas, 1 classic fibrosarcoma arising in dermatofibrosarcoma protuberans, 1 inflammatory myxohyaline tumor/myxoinflammatory fibroblastic sarcoma), myofibroma/myofibromatosis (n=12), nodular fasciitis (n=11), and scars (n=9). Nuclear and cytoplasmic staining was assessed. All 21 examples of deep fibromatosis displayed nuclear beta-catenin (focal nuclear staining in one case to 90% staining). All other lesions tested (n=67) lacked nuclear labeling for beta-catenin, showing only cytoplasmic accumulation. beta-Catenin immunohistochemistry separates deep fibromatosis from entities in the differential diagnosis, a finding that can be exploited for diagnosis. Most fibromatoses have diffuse nuclear staining although occasional examples only focally label.

Ectopic hamartomatous thymoma: a clinicopathologic and immunohistochemical analysis of 21 cases with data supporting reclassification as a branchial anlage mixed tumor.

This report describes the clinicopathologic and immunohistochemical findings in 21 cases of a highly distinctive tumor with a strong predilection for the lower neck region of adult males. Our study group consisted of 20 males and one female. The patients were 28 to 79 years old (mean age, 47 years; median age, 40 years), and they presented with solitary, lobular or multilobular masses ranging in size from 2.0 to 19.0 cm in greatest dimension (mean size, 5.1 cm; median, 4 cm). The tumors principally involved the lower neck region, usually in close proximity to the sternoclavicular joint. The preoperative duration of the lesions ranged from 2 months to 30 years. Histologically, the tumors were typically well marginated and composed of plump spindled cells, delicate spindled cells, mature adipose tissue, and epithelial cells, including both squamous and glandular elements. Epithelial-lined cysts were a focal finding in most cases and measured up to 2 cm in greatest dimension. Mitotic counts for the tumors ranged from 0 to 7 mitotic figures per 50 high power fields (mean mitotic count, 1.1 mitotic figures per 50 HPFs). Our immunohistochemical analysis revealed a complex immunophenotype with a diverse keratin profile. The plump spindled cells had a myoepithelial phenotype, as evidenced by the coexpression of keratins (5, 5/6, and 14), alpha-smooth muscle actin, CD10, and to a lesser extent, calponin. No compelling evidence for thymic differentiation was observed. The patients were initially managed by biopsy or partial resection (n = 4), simple local excision (n = 16), or an unspecified procedure (n = 1). Clinical follow-up of > or =3 years was available for 10 patients (48%). Two patients had recurrent disease, but there were no metastases or tumor-related deaths. A derivation from sequestered branchial epithelium is likely, but evidence for a thymic component is tenuous, at best. Our data support reclassification of this distinctive process as a branchial anlage mixed tumor. The differential diagnosis includes conventional mixed tumors of skin adnexal or salivary gland origin, synovial sarcoma, a peripheral nerve sheath tumor variant, and cystic teratoma.

Synovial-type giant cell tumors of the vertebral column: a clinicopathologic study of 15 cases, with a review of the literature and discussion of the differential diagnosis.

Synovial and tenosynovial giant cell tumors only rarely arise in close proximity to the axial skeleton; to date, fewer than 30 examples have been reported in the English-language medical literature. In this report we describe the clinical, radiologic, histopathologic, and immunohistochemical findings in 15 cases retrieved from our files. The study group comprised 7 males and 8 females, ranging in age from 17 to 44 years (mean age, 32 years). The tumors involved the cervical (n = 11), thoracic (n = 1), lumbar (n = 2), and sacrococcygeal (n = 1) regions and ranged in size from 1.0 to 6.0 cm in greatest dimension (median size, 3 cm). Symptoms were present for 2 months to at least 2 years, with the most common complaint being pain localized to the spinal region (n = 12). Ten patients also had radicular symptoms. Radiologic studies, available for 11 cases, usually demonstrated a mass involving the posterior aspect of adjoining vertebrae. Bony abnormalities (including scalloping, erosion, and destruction), facet joint and soft tissue involvement, and extradural extension were typically present. Histologically, all tumors contained a proliferation of epithelioid (histiocytoid) cells, admixed with varying numbers of osteoclast-like giant cells, siderophages, xanthoma cells, lymphocytes, and some spindled fibroblast-like cells. Only 1 tumor had the classic villiform architecture of pigmented villonodular synovitis. The remaining 14 tumors had a nodular appearance with varying amounts of collagen. Seven of these had definite histological evidence of infiltrative growth, and 6 had some features that warranted concern for possible infiltration. Only 1 tumor had findings fully compatible with a localized synovial-type giant cell tumor/nodular (teno)synovitis. All tumors had mitotic activity, with mitotic counts ranging from 1 to 21 mitotic figures per 50 high-power fields (HPFs) (mean mitotic count, 5 mitotic figures/50 HPFs). Immunohistochemistry was performed on 5 tumors, and immunoreactivity was present for CD68, CD163, and vimentin. Limited immunoreactivity for muscle actin (HUC1-1) was also noted. Follow-up information was available for 9 of the 15 patients (60%). Five patients had no evidence of recurrent or persistent disease 4 months to 9 years after undergoing either a local excision with gross total tumor removal (with or without irradiation) or a wide en bloc resection. Four patients had persistent disease after undergoing either an incomplete resection or biopsy with spinal fusion procedure. All 4 of these patients had additional surgical intervention (accompanied by irradiation in 2 instances), but only one was known to be disease-free at last follow-up (10 years after gross total tumor removal). No patient has experienced a metastasis or died of disease. The best predictor of outcome was gross total tumor removal at the surgical outset.

Healthy doctors, healthy communities.

Promoting health and eliminating disease are goals of Healthy People 2010, a national initiative for all communities. Physician-directed interventions that advance these principles are most effective when directed by clinicians who regularly participate in such healthy behaviors themselves. This pilot study describes an 8-week intervention, "Well-being for You and Your Patients," for first-year medical students to experience health behavior change. In the 2-hour sessions, students set goals for changing health behavior in 6 dimensions of wellness; report their progress; and enjoy a 30-minute change-of-pace wellness activity. The authors recommend adapting the course for medical student alumni to facilitate health behavior change with small groups of adults, school-age children, teens, and elders in churches, schools, community health centers, and other community-based organizations. Through continuing medical education and Grand Rounds, residents and physicians in practice could also be trained to implement specific behavioral change strategies.

Lipoma of the oral and maxillofacial region: Site and subclassification of 125 cases.

OBJECTIVE: Lipomas and lipoma variants are common soft tissue tumors, but occur infrequently in the oral and maxillofacial region. In this study, we reviewed 125 lipomas in specific oral and maxillofacial locations. We wanted to examine and compare the clinicopathologic features of these tumors. Study design The records from the Oral and Maxillofacial Pathology Registry of the Armed Forces Institute of Pathology from 1970 to the present were searched for cases coded as "lipoma." This study included 125 cases based on location within the oral and maxillofacial region, benign histology, and available clinical information. Subcutaneous and intraosseous lipomas were excluded. The tumors were classified according to the most recent World Heath Organization classification for soft tissue tumors. RESULTS: Of 125 lipomas, 91 tumors occurred in males, 33 in female patients, and 1 of unknown gender. The mean age was 51.9 years, range 9-92 years. Four tumors occurred in pediatric patients (age <18 years). Specific anatomic sites within the oral and maxillofacial region included the parotid region (n=30); buccal mucosa (n=29); lip (n=21); submandibular region (n=17); tongue (n=15); palate (n=6); floor of mouth (n=5); and vestibule (n=2). The mean size of tumors was 2.2 centimeters, range 0.5 to 8.0 centimeters. The mean duration of the tumors prior to excision was 3.2 years, range 6 weeks to 15 years. Most patients presented with an asymptomatic, circumscribed mass. Grossly, most tumors were described as pink and smooth, occasionally mucoid. Histologically, the tumors were subclassified as classic lipomas (n=62); spindle cell/pleomorphic lipomas (n=59); fibrolipoma (n=2), and chondroid lipoma (n=2). Fourteen tumors exhibited secondary changes, such as fat necrosis, atrophy, and prominent hyalinization; 23 tumors were histologically confirmed to be intramuscular. CONCLUSIONS: Lipomas of the oral and maxillofacial region occur most commonly in adult males in the parotid region, followed closely by the buccal mucosa. These tumors are uncommon in children. Interestingly, spindle cell lipomas are common in this region and comprise the majority of our parotid and lip tumors. Angiolipomas were absent in this anatomic region in this study. Secondary changes and atrophy should not be confused with the malignant histologic features of a liposarcoma.

Conditionally reprogrammed normal and transformed mouse mammary epithelial cells display a progenitor-cell-like phenotype.

Mammary epithelial (ME) cells cultured under conventional conditions senesce after several passages. Here, we demonstrate that mouse ME cells isolated from normal mammary glands or from mouse mammary tumor virus (MMTV)-Neu-induced mammary tumors, can be cultured indefinitely as conditionally reprogrammed cells (CRCs) on irradiated fibroblasts in the presence of the Rho kinase inhibitor Y-27632. Cell surface progenitor-associated markers are rapidly induced in normal mouse ME-CRCs relative to ME cells. However, the expression of certain mammary progenitor subpopulations, such as CD49f+ ESA+ CD44+, drops significantly in later passages. Nevertheless, mouse ME-CRCs grown in a three-dimensional extracellular matrix gave rise to mammary acinar structures. ME-CRCs isolated from MMTV-Neu transgenic mouse mammary tumors express high levels of HER2/neu, as well as tumor-initiating cell markers, such as CD44+, CD49f+, and ESA+ (EpCam). These patterns of expression are sustained in later CRC passages. Early and late passage ME-CRCs from MMTV-Neu tumors that were implanted in the mammary fat pads of syngeneic or nude mice developed vascular tumors that metastasized within 6 weeks of transplantation. Importantly, the histopathology of these tumors was indistinguishable from that of the parental tumors that develop in the MMTV-Neu mice. Application of the CRC system to mouse mammary epithelial cells provides an attractive model system to study the genetics and phenotype of normal and transformed mouse epithelium in a defined culture environment and in vivo transplant studies.

Goal-directed visuomotor skill learning: off-line enhancement and the importance of the primary motor cortex.

PURPOSE: The time course and neural substrates of motor skill learning are not well-understood in healthy or neurologic patient populations. Certain motor skills undergo off-line skill enhancement following training and the primary motor cortex (M1) may be involved. It is unknown if goal-directed visuomotor skill undergoes off-line enhancement or if M1 is associated with that enhancement. METHODS: 32 right-handed, healthy subjects were randomly assigned to two groups: real repetitive transcranial magnetic stimulation (rTMS) or sham rTMS applied to the contralateral M1 immediately following one 20-minute finger tracking training session. Tracking performance and cortical excitability were assessed before and after training, following rTMS and 24 hours post-training. RESULTS: Results demonstrate that skill performance continues to develop for at least 30 minutes after training completion, is maintained for 24 hours post-training, and is not affected by inhibitory rTMS applied to M1. Level of skill improvement was associated with the degree of intracortical inhibition increase. CONCLUSIONS: These results suggest dispersed information processing for goal-directed visuomotor skill learning following training and a relationship between cortical excitability and skill development in healthy individuals. These findings invite further investigation of the neural mechanisms underlying motor skill learning and may have rehabilitation implications for patients with neurologic injury.

Villonodular synovitis (PVNS) of the spine.

OBJECTIVE: To describe the imaging features of spinal pigmented villonodular synovitis (PVNS). DESIGN AND PATIENTS: We retrospectively reviewed 15 cases of pathologically proven spinal PVNS. Patient demographics and clinical presentation were reviewed. Radiologic studies were evaluated by consensus of two musculoskeletal radiologists for spinal location, spinal segments affected, lesion center, detection of facet origin and intrinsic characteristics on radiography (n=11), myelography (n=7), CT (n=6) and MR imaging (n=6). RESULTS: Women (64%) were more commonly affected than men (36%) with an average age of 28 years. Clinical symptoms were pain (45%), neurologic (9%) or both (36%). Lesions most frequently affected the cervical spine (53%) followed by the thoracic (27%) and lumbar regions (20%). The majority of lesions (93%) were centered in the posterior elements with frequent involvement of the pedicle (67%), neural foramina (73%), lamina (67%) and facets (93%). No lesions showed calcification. Determination of a facet origin by imaging was dependent on imaging modality and lesion size. A facet origin could be determined in 45% of cases by radiography vs 67% of patients by CT (n=6) and MR (n=6). Large lesions (greater than 3 cm in at least one dimension) obscured the facet origin in all cases with CT and/or MR imaging (44%,n=4). Small lesions (less than 3 cm in any dimension) demonstrated an obvious facet origin in all cases by CT and/or MR imaging (56%,n=5). Low-to-intermediate signal intensity was seen in all cases on T2-weighted MR images resulting from hemosiderin deposition with "blooming effect" in one case with gradient echo MR images. CONCLUSIONS: PVNS of the spine is rare. Large lesions obscure the facet origin and simulate an aggressive intraosseous neoplasm. Patient age, a solitary noncystic lesion centered in the posterior elements, lack of mineralization and low-to-intermediate signal intensity on all MR pulse sequences may suggest the diagnosis in these cases. Small lesions demonstrate a facet origin on CT or MR imaging. This limits differential considerations to synovial-based lesions and additional features of a solitary focus, lack of underlying disease or systemic arthropathy, no calcification as well as low-to-intermediate signal intensity on all MR images should allow spinal PVNS to be suggested as the likely diagnosis.

Hemangioma of the salivary gland: a study of ten cases of a rarely biopsied/excised lesion.

Hemangioma is a common soft tissue tumor that frequently occurs in the oral and maxillofacial region including salivary glands, but is rarely biopsied and is therefore often unfamiliar to the surgical pathologist. Our study examined the subclassification and histologic features of salivary gland hemangioma (SGH). Consultative cases coded as hemangioma and located in salivary gland from 1970 to 2000 were retrieved from the Registry of Oral and Maxillofacial Pathology of the Armed Forces Institute of Pathology (Washington, DC). Only cases with histologic evidence of salivary gland involvement were included. Slide material and patient history for all cases were reviewed, subclassification assigned, and histologic features were noted. Ten cases coded as hemangioma with slides and history met our inclusion criteria. Seven cases were the "juvenile hemangioma" subtype in the parotid of infants, ranging in age from 3 to 10 months (mean age, 5.3 months) with a male predominance. These SGH had a distinctive histologic appearance of a cellular proliferation of capillary sized vessels around retained salivary gland ducts. Mitoses were easily identified. Three additional cases in females included an arteriovenous hemangioma of a lip minor salivary gland since birth in a 15-month-old infant and two parotid gland lesions: a lobular capillary hemangioma of a 10-year-old and a cavernous hemangioma in a 51-year-old. The latter three cases grew as replacing masses and lacked retained salivary gland ducts within the lesion, despite glandular tissue at the periphery of the tumor. No SGH cases in our series were identified in the submandibular or sublingual glands. Despite its common occurrence, SGH is relatively rare in our surgical pathology files. The parotid gland is the most common location (90%). Salivary gland hemangioma includes usual hemangioma subtypes, mainly in females, and a distinctive infantile subtype of capillary hemangioma (juvenile hemangioma), displaying distinctive histology and found predominately in males. The cellularity, mitotic activity, and retained salivary gland ducts in the latter lesion should not make one consider malignancy.

Liposarcoma of the oral and salivary gland region: a clinicopathologic study of 18 cases with emphasis on specific sites, morphologic subtypes, and clinical outcome.

Liposarcoma is rare in the oral and salivary gland region (OSG), previously described in only case reports and two small series. Clinicopathologic features of a large series of these tumors were studied. Cases coded as "liposarcoma or lipoma" from 1970 to 2000 were searched for in our files. Inclusion required an OSG location and diagnosis by established soft tissue criteria. Dermal, other soft tissue, and intraosseous liposarcomas were excluded. Clinical and pathologic material was reviewed and follow-up obtained. Eighteen liposarcomas were included: 10 from males and 8 from females. The median patient age was 51 years (range, 30-70 years). Specific anatomic locations included buccal mucosa (n = 7), tongue (n = 4), parotid gland (n = 3), soft tissue overlying the mandible (n = 2), and one each of palate and submandibular gland. The average tumor size was 4.2 cm (range, 1.5 to 6.0 cm). Histologically, most tumors were well differentiated, including one atypical lipoma (n = 10), followed by myxoid (n = 5) and dedifferentiated (n = 3). OSG liposarcomas of all subtypes had increased numbers of lipoblasts. All patients were treated with surgical excision alone. Follow-up on 15 patients (83%) over a mean of 16.5 years (range, 2 to 53 years) revealed that three patients had between one and six local recurrences over periods of 18 months to 6 years. Twelve patients were without recurrence, with a mean follow-up of 12.8 years (range, 2-23 years). No patients, including those with dedifferentiated liposarcoma, had metastases or died of disease. OSG liposarcomas are rare tumors of adults, occurring most commonly in the buccal mucosa, tongue, and then parotid gland. There were no pleomorphic liposarcomas in this series; well-differentiated liposarcoma was the most common subtype, which can locally recur but, even with high-grade dedifferentiation, does not necessarily predict poor outcome. Therefore, OSG liposarcomas have better prognosis than liposarcoma in other soft-tissue locations, perhaps based on smaller size at presentation. Complete local excision and careful patient follow-up, without adjuvant therapy, appears to be the best treatment for OSG liposarcoma.

Oral and salivary gland angiosarcoma: a clinicopathologic study of 29 cases.

Angiosarcomas of the oral and salivary gland area are extremely rare, mostly presented as case reports. We wanted to study the clinicopathologic features of a series of oral and salivary gland angiosarcomas. Cases coded as "angiosarcoma" were retrieved from the Oral and Maxillofacial Pathology Department of the Armed Forces Institute of Pathology. Patient folders and pathology were reviewed and recorded; immunohistochemistry and follow-up were obtained. Inclusion required oral or salivary gland location, vasoformative growth, cytologic atypia, mitoses, and vascular markers. Skin, bone, and subcutaneous angiosarcomas were excluded. Primary and secondary (metastatic) oral angiosarcomas were included. The 22 primary angiosarcomas involved tongue (n = 9), parotid (n = 4), lip (n = 4), submandibular gland (n = 3), and 1 each of soft and hard palate. The 7 secondary angiosarcomas involved the gingiva (n = 4) and parotid gland (n = 3). Overall, patient ages ranged from 6-90 years (mean, 55 years). There were 15 males and 14 females. Symptoms included a mass with recent enlargement and bleeding. Tumor sizes ranged from 0.8-7.0 cm (mean, 2.6 cm). Histologically, all tumors were vasoformative; 86% had solid and 17% had distinctive papillary areas. Eight (28%) were classified as the epithelioid subtype. Immunohistochemical stains showed that the tumor cells were positive for Factor VIIIrag in 19/21, CD31 in 16/19, CD34 in 7/12, and Ulex in 1/1. Primary tumors were classified as low grade (n = 7, in all locations except salivary gland), intermediate (n = 7), and high grade (n = 8); all secondary tumors were high grade. Follow-up was available on 14/22 primary and 7/7 secondary angiosarcomas. Of primary tumors, two tongue angiosarcoma patients died at 1 and 9 years, but 4 were alive without disease over a mean of 7.3 years (range, 1-13 years). Four primary salivary gland angiosarcoma patients were alive without disease over a mean of 5.8 years (range, 1-14 years), and 1 had only a late (15 years) metastasis and death (at 20 years). Three primary lip angiosarcoma patients were without disease over a mean of 14.3 years (range, 13-16 years). Of secondary tumors, three salivary gland angiosarcoma patients died within 1 year, and all four secondary gingival angiosarcoma patients died of disease within 3 years. Assessing follow-up of primary oral and salivary gland angiosarcoma patients by grade, 5 patients with high-grade tumors had no evidence of disease over a mean of 7.6 years (range, 1-16 years), 3 patients with intermediate-grade tumors had no evidence of disease over a mean of 12.7 years (range, 11-14 years), 2 patients with intermediate-grade tumors died of disease at 9 and 20 years, 3 patients with low-grade tumors had no evidence of disease over a mean of 6.3 years (range, 1-14 years), and 1 patient with low-grade tumor died of disease at 1 year. Primary oral and salivary gland angiosarcomas, albeit rare, mostly involve the tongue, parotid gland, and lip of adults, often with relatively good outcome. Although the most common angiosarcoma morphology in this area is spindled vasoformative and solid, almost one third of oral and salivary gland angiosarcomas are the rare epithelioid angiosarcoma variant. Most gingival and few parotid angiosarcomas appear to be metastases from other locations, with many patients succumbing to death within 3 years. Despite predominantly high- or intermediate-grade morphology, patients with primary angiosarcoma of the tongue, salivary gland, and lip have a better prognosis than do patients with primary cutaneous or deep soft tissue angiosarcoma, including those patients with secondary oral and salivary gland involvement.