PD-L1 expression in sarcomas: An immunohistochemical study and review of the literature.

BACKGROUND: Immunotherapy is increasingly used for treatment of metastatic melanoma and carcinomas. PD-1 (programmed death 1) and its associated ligand (PD-L1) inhibits the activation of T-lymphocytes. This inhibition can be impacted by a number of drugs. Response to these drugs is predicted by assessment of PD-L1 expression. PD-L1 expression varies between 19% and 92% in melanomas and carcinomas. PD-L1 expression is less well documented for sarcomas. DESIGN: Fifty-six sarcomas of various histopathologic types were immunohistochemically stained (IHC) for PD-L1 using the antibody clone SP263 (Ventana, Tuscan, AZ). Membrane staining of tumor cells was quantitated as a percentage of total tumor cells. Sarcomas were judged as non-expressors (less than 1%) low-expressors (1 to 50%) and high expressors (greater than 50%). The percentage of each type of sarcoma judged as an expressor was determined. RESULTS: Table 1 documents the percentage of each type of sarcoma expressing PD-L1. 14% of sarcomas expressed PD-L1. Percentage of sarcomas expressing PD-L1 varied significantly between types but the majority of sarcomas were non-expressors. CONCLUSION: PD-L1 IHC expression is valuable in predicting response to immune-modulating drugs. Such therapies may be useful for treatment of metastatic sarcomas. Expression of PD-L1 in carcinomas and melanomas is variable ranging from 19% to 92%. In our study, a minority (14%) of sarcomas expressed PD-L1. Other studies have shown similar results with between 1.4 and 59% (average 24%) of sarcomas expressing PD-L1. Expression appears to be sarcoma type specific. These finding suggest that PD-L1 based therapy may be less useful in sarcomas than in other malignancies.

Angiomatoid fibrous histiocytoma: novel MR imaging findings.

OBJECTIVE: To describe novel MR imaging features, and clinical characteristics of soft tissue angiomatoid fibrous histiocytoma (AFH) at presentation, local recurrence, and metastases. MATERIALS AND METHODS: We described the MRI findings of six cases of histologically proven AFH. Pathologic findings, clinical presentation, and outcome were reviewed. RESULTS: Lesions were primarily cystic. At initial presentation, tumors were surrounded by low signal intensity fibrous pseudocapsule. High signal intensity consistent with the lymphoplasmacytic infiltrate was seen in T2-weighted and post-contrast images as a rim over the hypointense pseudocapsule (double rim sign). High signal intensity infiltrating tumoral cords extended into adjacent tissues, through pseudocapsular defects on T2-weighted and post-contrast images. The cystic component and tumor cell nodularity were demonstrated at post-contrast images. Clinically, lesions were often thought to be benign, underwent marginal resection, developed local recurrence, and one developed second recurrence consisting of metastases. Recurrent tumors appeared as multiple masses, misinterpreted as post-surgical changes. An intramuscular recurrence demonstrated double rim and infiltrating margin. CONCLUSIONS: A predominantly well-circumscribed, primarily cystic mass with double-rim and marginal infiltration on MRI suggests the possibility of AFH, in particular in child or young adult. Inclusion of these novel observations in AFH differential diagnosis may have a significant impact on treatment and prevention of recurrence.

A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins.

The goal of resection of soft tissue sarcomas located in the extremity is to preserve limb function while completely excising the tumor with a margin of normal tissue. With surgery alone, one-third of patients with soft tissue sarcoma of the extremity will have local recurrence due to microscopic residual disease in the tumor bed. Currently, a limited number of intraoperative pathology-based techniques are used to assess margin status; however, few have been widely adopted due to sampling error and time constraints. To aid in intraoperative diagnosis, we developed a quantitative optical microscopy toolbox, which includes acriflavine staining, fluorescence microscopy, and analytic techniques called sparse component analysis and circle transform to yield quantitative diagnosis of tumor margins. A series of variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82 and 75%. The utility of this approach was tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78 and 82%. For comparison, if pathology was used to predict local recurrence in this data set, it would achieve a sensitivity of 29% and a specificity of 71%. These results indicate a robust approach for detecting microscopic residual disease, which is an effective predictor of local recurrence.

Needle biopsy of mesenchymal lesions of the head and neck: Evolving concepts and new strategies for diagnosis.

Sarcomas are a rare and heterogeneous group of neoplasms that can be a significant diagnostic challenge in routine practice. Recent advances in the understanding of molecular mechanisms underlying oncogenesis have led to an array of novel diagnostic tools. Here we review several sarcomas of the head and neck region, focusing on neoplasms with new molecular findings and highlighting novel diagnostic tools.

Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) is one of the most common soft tissue malignancies. Patients with large, high-grade sarcomas often develop fatal lung metastases. Understanding the mechanisms underlying sarcoma metastasis is needed to improve treatment of these patients. Micro-RNAs (miRNAs) are a class of small RNAs that post-transcriptionally regulate gene expression. Global alterations in miRNAs are frequently observed in a number of disease states including cancer. The signalling pathways that regulate miRNA biogenesis are beginning to emerge. To test the relevance of specific oncogenic mutations in miRNA biogenesis in sarcoma, we used primary soft tissue sarcomas expressing either Braf(V600E) or Kras(G12D). We found that Braf(V600E) mutant tumours, which have increased MAPK signalling, have higher levels of mature miRNAs and enhanced miRNA processing. To investigate the relevance of oncogene-dependent alterations in miRNA biogenesis, we introduced conditional mutations in Dicer and showed that Dicer haploinsufficiency promotes the development of distant metastases in an oncogene-dependent manner. These results demonstrate that a specific oncogenic mutation can cooperate with mutation in Dicer to promote tumour progression in vivo.

World Health Organization Reporting System for Soft Tissue Cytopathology: Risk of malignancy and reproducibility of categories among observers.

INTRODUCTION: In 2024, the World Health Organization (WHO) is scheduled to publish the WHO Reporting System for Soft Tissue Cytopathology (WHORSSTC). This system establishes categories with well-defined definitions, criteria, and estimated risks of malignancy (ROMs) for soft tissue tumors. The estimates of ROM are based on a relatively small number of published studies. Interobserver reproducibility is not addressed in the reporting system even though reproducibility of a reporting system is highly important. METHODS: A manual search of one authors personal consultation files and teaching set (L.J.L.) was conducted for all cytologic specimens of soft tissue tumors accessioned between January 1, 1985 and December 31, 2022. Only cases with documented surgical pathology follow-up were included in the study. Slides from each case were evaluated independently by three cytopathologists with each case assigned to one of the WHORSSTC categories. A ROM for each of the WHORSSTC categories was calculated. Interobserver agreement was evaluated by the kappa and weighted kappa statistics. RESULTS: Risk for malignancy by category were: Category 1: 0%, Category 2: 28%, Category 3: 57%, Category 4: 47%, Category 5: 63%, and Category 6: 88%. Kappa statistics for agreement between raters varied from 0.2183 to 0.3465 and weighted kappa varied from 0.3778 to 0.5217. CONCLUSIONS: The WHORSSTC showed a progression of malignancy risk from the category "benign" (28%) to the category "malignant" (88%). Interobserver agreement was only fair.

Cytological diagnosis of follicular dendritic cell sarcoma with a unique pattern of D2-40 immunoexpression.

Fine needle aspiration procedure is routinely used for cytological diagnosis of nodal or extra nodal lesions. Follicular dendritic cell sarcoma (FDCS) is a rare mesenchymal neoplasm arising from follicular dendritic cells of lymphoid follicles at nodal and extranodal sites. Multimodal therapies have emerged for FDCS, necessitating its accurate pathologic diagnosis with additional ancillary testing for directing clinical management. By immunohistochemical analysis, FDCS is positive for the complement receptors CD21, CD23, and CD35. In addition, D2-40 is reported to be highly sensitive for FDCS with a strong membranous pattern of expression. In this study, we present the cytological diagnosis of a case of FDCS in retroperitoneal lymph nodes with an emphasis on a unique staining pattern of D2-40 which showed a strong nuclear pattern in tumor cells comparable to the membranous pattern of D2-40 on the control tissue and other surgical cases of FDCS in our comparative study.

Healers and midwives accused of witchcraft (1563-1736) - What secondary analysis of the Scottish survey of witchcraft can contribute to the teaching of nursing and midwifery history.

BACKGROUND: Nearly 4000 people were accused of witchcraft in Scotland between 1563 and 1736. Some of these were healers, midwives, and nurses. OBJECTIVE: To investigate Scotland's folk-healers and midwives accused of witchcraft and review their work from a nursing and midwifery perspective. DESIGN: Secondary analysis of the Survey of Scottish Witchcraft. METHODS: Those on the Survey with witchcraft accusations relating to folk-healing or midwifery were identified and their biographies were created from Survey data (2021). Individual biographical data were descriptively analysed. Healing/midwifery practice information was tabulated and thematically analysed. RESULTS: 142 individuals were identified (85 % women), 51 % were found guilty, 90 % were executed. Most (98 %) were folk-healers with 10 accused for midwifery reasons. Mainly their work was accused of causing harm. Three themes emerged: their use of rituals; unorthodox religious practices and treatments. Rituals included actions carried out a certain number of times. Religious practices frequently referenced Catholicism. Many of their treatments for ingestion, application or bathing used items still recognised for their health properties. Approximately, 10 % of the 142, mainly in the 1500s/early 1600s, utilised expensive items and complex treatments which had more in common with 'elite' knowledge rather than simple folklore. CONCLUSIONS: Across all 142 people, many aspects of their work are identifiable within more contemporary nursing and midwifery practice including their use of rituals, treatments, and holism. Mostly the accused were folk-practitioners, but a few (1500s/early 1600s) appear to have been healers working akin to physicians. Following the Protestant reformation (1560) their work, unlike that of physicians, was marginalised, considered unorthodox and harmful because they were women and/or their work reflected Catholicism. European hospital nursing originates in the monastic houses, but little is known about these early religious nurses. This study is novel in suggesting that whoever taught these accused witch/healers may have been connected to the monastic hospitals pre-Reformation.

Imaging of recurrent intramuscular granulomatous masses induced by depot injection of leuprorelin.

Leuprorelin is a luteinizing hormone-releasing hormone (LH-RH) agonist that is used as an agent of androgen deprivation in some patients with prostate cancer. When administered in depot form, local granulomatous reactions may occur at the injection site, which may mimic masses and which are associated with treatment failure. We present a patient who, over a period of 5 years, developed multiple intramuscular gluteal masses while receiving leuprorelin therapy via intramuscular depot injections; biopsy of one of the masses showed the specific histologic features of leuprorelin granuloma. To our knowledge, this entity has not been described in the radiology literature. Awareness of this entity is necessary to suggest the correct diagnosis in patients with a history of leuprorelin depot injections.

Pseudotear of the peroneus longus tendon on MRI, secondary to a fibrocartilaginous node.

OBJECTIVE: The purpose of this study was to identify the presence of a fibrocartilaginous node within the distal peroneus longus tendon (PLT) just proximal to the cubital tunnel and correlate this with MRI signal characteristics of the distal PLT, which could result in a pseudotear appearance on MRI. We correlated imaging characteristics with pathologic specimens. MATERIALS AND METHODS: Institutional review board approval was obtained. Retrospectively, 91 ankle MRIs utilizing a standard ankle protocol were reviewed by two musculoskeletal radiologists. Four cadaver ankles were imaged using a standard ankle MRI protocol and reviewed by the same radiologists. All the MRIs were examined for signal changes in the PLT. The cadaver ankles then underwent PLT dissection by an orthopaedic surgeon, and a pathologic review was undertaken by a pathologist with orthopaedic specialization, who looked for an os peroneum or proposed fibrocartilaginous node relating to the signal change found on the MRIs. RESULTS: In the 91 ankle MRI studies, the PLT demonstrated normal low and increased signals. On the fat-saturated T2-weighted sequence, 76 (83.5%) ankles demonstrated low signal and 15 (16.5%) demonstrated increased signal. Of the cadaver ankle MRIs, all four demonstrated increased signal within the PLT; three contained a fibrocartilaginous node and one contained an os peroneum in that same region. CONCLUSIONS: The MRI signal of the PLT can change with the presence of a fibrocartilaginous node, which may be due to the molecular and chemical content of the fibrocartilage. This node increases the MRI signal in the distal PLT and gives the appearance of a pseudotear.

Leiomyosarcoma of the somatic soft tissues.

Leiomyosarcomas of the somatic soft tissues are tumors of smooth muscle origin that occur in the extremities. These lesions are commonly high-grade tumors that carry a poor prognosis. Recommended treatment often includes wide excision and chemotherapy or radiation therapy. Sixty-five patients were followed for a mean of 4.1 years. The mean maximum tumor diameter was 7 cm, and approximately 70% of all patients had tumors deep to fascia. Including all stages of disease, the overall 1-, 2-, and 5-year survival rates were 91%, 87%, and 68%, respectively. Mitotic rate and tumor depth were significant predictors of development of recurrent disease and metastatic disease. Tumor size was another predictor of recurrent disease. The mitotic rate and AJCC stage were also important predictors of overall survival. Patients with deep lesions, histologic grade 3 disease/higher mitotic rates, and advanced stage of disease had a poorer prognosis and thus were more likely to undergo adjuvant chemotherapy. Future clinical studies may help determine if knowledge of these predictors can help guide treatment and improve clinical outcomes.

Cytomorphology of spindle cell/sclerosing rhabdomyosarcoma, including MYOD1 (LI22R) mutation result.

Spindle cell/sclerosing rhabdomyosarcoma (RMS), characterized by MYOD1 (L122R) mutation in a subset of cases is a newly described subtype of RMS. Presently, there is no documentation of cytomorphological features, especially of sclerosing RMS. Case 1: A 24-year-old male presented with pain and swelling in his wrist for a one-year duration. MRI revealed a well-defined soft tissue lesion measuring 5.3 cm, encasing the lower end of the ulna. Fine-needle aspiration cytology (FNAC) smears revealed clusters of tumor cells with round to oval to spindle-shaped nuclei, scant to moderate amount of cytoplasm with the wisps of the metachromatic stroma. Histopathological examination revealed a malignant tumor comprising cells with polygonal to spindle-shaped nuclei, arranged in a sclerotic stroma. Immunohistochemically, the tumor cells were positive for desmin, myogenin, and MYOD1. A diagnosis of sclerosing RMS was offered. Furthermore, the tumor revealed MYOD1 (L122R) mutation. Case 2: A 43-year-old male presented with a 4-month history of "nasal stuffiness" and pressure. Imaging revealed a poorly defined infiltrative lesion in his nasal cavity. FNAC smears revealed loose and tightly cohesive clusters of malignant cells with oval to spindle-shaped nuclei, a moderate amount of ill-defined bluish to finely vacuolated cytoplasm, and focal streak artifact with interspersed stromal fragments. Histopathological examination revealed a malignant tumor composed of oval to spindle-shaped nuclei, embedded in a variably hyalinized stroma. Immunohistochemically, the tumor cells were positive for desmin, and myogenin. Diagnosis of spindle cell/sclerosing RMS was offered. The present study constitutes one of the first documentation of cytomorphological features of two rare cases of spindle cell/sclerosing RMS. The differential diagnoses and treatment-related implications are presented.

A case of osteoclastic variant of anaplastic thyroid carcinoma: Diagnostic and prognostic marker studies by cytology.

Anaplastic thyroid carcinoma is an infrequent, but aggressive fatal subtype of thyroid cancer. The osteoclastic variant of anaplastic carcinoma is a rare subtype of anaplastic carcinoma with rare cases reported in the literature. Molecular targeted therapies have emerged for the anaplastic carcinoma, necessitating accurate pathologic diagnosis with additional ancillary testing for directing clinical management. We present here the cytological diagnosis of an anaplastic thyroid carcinoma-osteoclastic variant on fine-needle aspiration (FNA), with emphasis on the novelty of utilizing the least invasive procedure (aspiration cytology) for rendering pathological diagnosis as well as identifying potential prognostic markers for targeted immunotherapy.

Crystals and crystalloids in cytopathology: Incidence and importance.

Many crystals and crystal-like structures may be encountered in cytopathology practice and can represent both beautiful novelties and diagnostic aids. The authors present an organ-specific review of the published literature on crystals combined with personal experiences. The purpose is not only to serve as a reference guide by highlighting the clinical and morphologic features of crystals, crystalloids, and crystal-like structures but also to review their significance and to offer reporting strategies in cases that bear management implications.

Performance of specific morphologic features in distinguishing low-grade squamous intraepithelial lesions from high-grade squamous intraepithelial lesions in borderline cases: a College of American Pathologists Cytopathology Committee multiobserver study.

INTRODUCTION: Distinguishing between low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) can be difficult on certain Papanicolaou (Pap) tests, hindering interobserver concordance. We investigated the variables influencing the interpretation of LSIL versus HSIL in Pap test slides rejected from the College of American Pathologists PAP education program. MATERIALS AND METHODS: Eleven cytologists, who were unaware of the reference interpretation, examined 21 Pap slides (11 submitted as LSIL and 10 as HSIL) rejected from the PAP education program and recorded the number of LSIL cells, HSIL cells, keratinized dysplastic cells, LSIL clusters with mixed HSIL cells, atypical squamous metaplasia, atypical glandular cells, the presence of inflammation or infectious organisms, and the overall interpretation (LSIL or HSIL). We evaluated the significance of these 11 variables using a nonlinear mixed model analysis. RESULTS: LSIL had greater concordance (92 of 121 responses; 76.0% concordance) than HSIL (68 of 110 responses; 61.8% concordance; P < 0.001). The only predictors of misclassified cases were the number of atypical squamous metaplastic cells and the number of HSIL cells (P < 0.001). The more of these cells identified, the more likely the reviewers were to classify the slide as HSIL. The reproducibility of the diagnosis was fair (Gwet's agreement coefficient, 0.33). CONCLUSIONS: Interobserver reproducibility is a challenge for a subset of cases with features intermediate between LSIL and HSIL. Atypical squamous metaplasia and dysplastic nuclei with a nuclear/cytoplasmic ratio greater than one half of the cell volume (HSIL) present on a Pap test influenced the likelihood that a reviewer would interpret the case as HSIL rather than LSIL.

Case report: lead toxicity associated with an extra-articular retained missile 14 years after injury.

Lead toxicity associated with extra-articular retained missiles (EARMs) is an uncommon yet potentially devastating complication of gunshot wounds. While the risk of lead toxicity with intra-articular retained missiles is well-known, EARMs are routinely permitted to remain in tissues indefinitely without surveillance for lead toxicity. We present a 34 year-old man who was found to have symptomatic lead toxicity 14 years after sustaining a gunshot-associated femoral fracture with retention of lead bullet fragments. A fluid-filled cyst containing two large lead bullet fragments was identified intraoperatively. Whole-blood lead concentration decreased after removal of the lead-filled cyst. Cyst formation and concomitant bone fracture are two of the risk factors for lead toxicity in patients with EARMs after gunshot wounds. Recognizing risk factors for EARM-associated elevation in lead levels is important as the adverse effects of increased lead burden may be asymptomatic and difficult to diagnose, yet debilitating and potentially lethal.

Myxoid neoplasms of bone and soft tissue: a pattern-based approach.

INTRODUCTION: The accurate diagnosis of musculoskeletal neoplasms is difficult but a pattern-based approach combined with ancillary testing has been shown to improve diagnostic accuracy. The pattern-based approach is particularly appropriate for myxoid lesions. MATERIALS AND METHODS: The authors reviewed their personal experience of over 3 decades of diagnosing myxoid neoplasms of musculoskeletal lesions. RESULTS: The authors found that myxoid lesions can be accurately classified based on cell type, nuclear atypia, presence of blood vessel fragments, as well as the results of immunohistochemical and molecular testing. CONCLUSIONS: Musculoskeletal lesions with a prominence of myxoid or chondroid material in the background can be accurately diagnosed using pattern analysis and ancillary testing.

Making the diagnosis of acute appendicitis: do more preoperative CT scans mean fewer negative appendectomies? A 10-year study.

PURPOSE: To determine the frequency of preoperative computed tomography (CT) in the evaluation of patients suspected of having appendicitis at one institution during the past 10 years and to determine whether changes in CT utilization were associated with changes in the negative appendectomy rate. MATERIALS AND METHODS: Institutional review board approval was obtained, and a waiver of informed consent was granted for this HIPAA-compliant study. A surgical database search yielded medical record numbers of 925 patients (526 [ 56.9%] men and 399 [43.1%] women; mean age, 38 years (range, 18-95 years]) who underwent urgent appendectomy between January 1998 and September 2007. Patients who were younger than 18 years of age at the time of surgery were excluded. CT, pathology, and surgery reports were reviewed. By using logistic regression, changes in the proportion of patients undergoing CT and in the proportion of patients undergoing each year appendectomy in which the appendix was healthy were evaluated. Subgroup analyses based on patient age ( 45 years) and sex also were performed. RESULTS: Prior to urgent appendectomy, 18.5% of patients underwent preoperative CT in 1998 compared with 93.2% of patients in 2007. The negative appendectomy rate for women 45 years of age and younger decreased from 42.9% in 1998% to 7.1% in 2007. However, the timing of the decline in negative appendectomy rates for women 45 years and younger could not be proved to be associated with the increase in CT use. There was no significant trend toward a lower negative appendectomy rate for men regardless of age or for women older than 45 years of age with increased use of preoperative CT. The shift from single-detector CT to multidetector CT and the use of decreasing section thickness also correlated with a reduction in false-positive diagnoses. CONCLUSION: Rising utilization of preoperative CT and advances in technology coincided with a decrease in the negative appendectomy rate for women 45 years and younger but not in men of any age or women older than 45 years.

Carcinoid tumors of the appendix: are these tumors identifiable prospectively on preoperative CT?

The purpose of this study was to determine if carcinoid tumors of the appendix were identified prospectively on preoperative CT at our institution during the last decade. A surgical database search performed using the Current Procedural Terminology codes for appendectomy and colectomy yielded 2108 patients who underwent appendectomy or colectomy with removal of the appendix from January 1998 through September 2007. Pathology reports were reviewed to identify patients in whom an appendiceal carcinoid tumor was identified. Preoperative CT reports and images were reviewed. Twenty-three carcinoid tumors (1.1%; 15 women [65.2%], eight men [34.8%]; average age 54 years [range, 23 to 86 years]) were identified. Ten patients underwent preoperative CT. No tumors were identified prospectively on CT. Images were available for rereview for eight patients. Studies were acquired with 16- (n = 7) and four- (n = 1) slice CT scanners. Average reported tumor size was 6.1 mm (range, 1.5 to 15 mm; n = 18). A tip or distal location was reported for all tumors for which a location was given (n = 15). Carcinoid tumors occurred in 1.1 per cent of appendix specimens. These tumors were all less than or 1.5 cm in size. Likely as a result of their small size, none of these tumors was identified prospectively on preoperative CT.

Extremity soft tissue sarcomas presented as hematomas.

INTRODUCTION: Soft tissue sarcoma (STS) with extensive intra-tumoral hemorrhage is an infrequently described entity, usually misdiagnosed as intra-muscular hematoma. The outcomes in this group of patients have not been previously described. MATERIALS AND METHODS: We retrospectively identified 15 patients, with initial clinical or imaging diagnosis of hematoma, or hematoma versus hemorrhagic sarcoma, although final diagnosis of high-grade STS was established in all cases. RESULTS: The most common location was the thigh. Three patients had a bleeding predisposition. Ten patients were referred for further evaluation with the initial diagnosis of muscle strain/hematoma, hematoma versus abscess in one, whereas four were referred for soft tissue mass evaluation. Final diagnosis was made by one biopsy in only 53% of patients. Mean time to diagnosis for patients with two biopsies was 7 months from initial presentation. Histologic diagnosis was malignant fibrous histiocytoma in ten patients. Surgical treatment included tumor resection in eleven and amputation in three patients. One patient had lung metastatic disease at presentation and eight developed lung metastases within a median time of 7 months. CONCLUSION: We suggest that an STS masquerading as hematoma should be suspected when the mechanism and the energy of the trauma do not justify the clinically detected severity of the injury, or the lesion does not follow the expected clinical course of resolution after initial conservative management. Bleeding predisposition does not exclude malignancy. The evacuation of hematomas should include pathologic examination of tissue. Prognosis is dismal due to early metastatic disease.