John S. Brooks

Primary cardiac sarcomas: a clinicopathologic analysis of a series with follow-up information in 17 patients and emphasis on long-term survival

Although cardiac sarcomas are rare in comparison to their soft tissue counterparts, they are the second most common type of primary cardiac neoplasm. Of the few hundred cases reported, most has been based on autopsy series. A series of 27 cardiac sarcomas removed at surgery for curative and diagnostic intent were reviewed for clinicopathologic features with correlation to available postoperative follow-up data in 17 patients. There were 6 angiosarcomas, 6 myxofibrosarcomas, 3 malignant peripheral nerve sheath tumors, 3 leiomyosarcomas, 2 synovial sarcomas, 1 epithelioid hemangioendothelioma, 1 chondrosarcoma, 1 osteosarcoma, and 4 poorly differentiated sarcomas. There was a wide age and size range with slight female predilection. There were 20 cases that arose in the atria/pulmonary vessels, 4 in the ventricles, 1 in mitral valve, and 2 in epi/pericardium. There was a slight left predilection. The histologic grade was low in 4, moderate in 3, and high in 20 cases. Six high-grade and 1 low-grade tumors were also treated with adjuvant chemotherapy and/or radiation. In 17 patients with follow-up data, 6 of 12 patients with high-grade tumor died (4 within 5 days of the initial surgery, 1 in 21 months, and 1 in 131 months), and 1 patient with moderate-grade tumor and all 4 patients with low-grade tumor were alive without evidence of disease at the end of follow-up. Tumor grade appeared to be prognostically important in cardiac sarcoma. Long survival was achieved in patients who survived the initial surgery well.

Eosinophils as a marker for invasion in cervical squamous neoplastic lesions.

A study of eosinophils associated with cervical neoplastic squamous epithelium was undertaken to determine whether their presence is a marker for invasion. Forty cervical incisional biopsy specimens of high-grade squamous intraepithelial neoplasia (HSIL), 12 with an element of invasive carcinoma, and 2 of HSIL suspicious for invasion, and follow-up excisional specimens of 27 cases of HSIL and 6 of microinvasive and invasive carcinoma were reviewed. In both incisional biopsy and excisional specimens, the presence of ≥5 eosinophils/high-power fields (hpf) and ≥10 eosinophils/10 hpf were both highly significantly associated with invasion with a high degree of specificity and positive predictive value, whereas counts below these thresholds had a high negative predictive value. The authors propose: 1) eosinophil counts in cervical incisional biopsy specimens of ≥5/hpf and/or ≥10/10 hpf warrant a note of caution that invasion may be present even when none is identified in the specimen by conventional criteria; 2) eosinophil counts of ≥5/hpf and/or ≥10/10 hpf in excisional biopsy and hysterectomy specimens should raise the suspicion of invasion in cases in which only HSIL is identified in the initial sections, and warrant additional sections and/or levels to search for invasion; and 3) the above eosinophil counts may provide supportive evidence for invasion in cases with equivocal invasion by conventional criteria.

TFE3 expression in tumors of the microphthalmia-associated transcription factor (MiTF) family.

The DNA-binding factor TFE3 is closely related to microphthalmia-associated transcription factor (MiTF) and is over-expressed in alveolar soft part sarcoma (ASPS) and select renal cell carcinomas. Reports of TFE3 expression in PEComa prompted investigation into TFE3 expression among other members of the putative MiTF group of neoplasms. The authors examined cases of PEComa (n = 6), conventional angiomyolipoma (AML; n = 22), metastatic melanoma (n = 16), and clear cell sarcoma (CCS; n = 9) for TFE3 expression. Nuclear immunostaining was observed in 74% (39/53) of cases, as follows: 5/6 PEComas, 18/22 AMLs, 10/16 metastatic melanomas, and 6/9 CCSs. However, with the exception of PEComas, compared with ASPS controls, TFE3 staining was significantly less intense in the tumors examined. These results illustrate that TFE3 immunoreactivity is detectable in other members of the MiTF family of neoplasms. For this reason, such neoplasms warrant consideration in the differential diagnosis with nuclear TFE3 immunoreactivity, particularly when staining is focal and less intense.

MUM-1 expression differentiates tumors in the PEComa family from clear cell sarcoma and melanoma.

PEComas are mesenchymal neoplasms composed of perivascular epithelioid cells (PEC) and include a spectrum of tumors. PEComas and malignant melanoma share common morphological, immunohistochemical, and ultrastructural features, such as epithelioid cell morphology and melanocytic immunophenotype. Melanocytic markers commonly expressed in PEC tumors include HMB-45, Melan-A/MART-1, tyrosinase, microphthalmia transcription factor (MITF), and occasionally, S100. Given this morphological and immunophenotypical overlap, the differential diagnosis between a PEComa and malignant melanoma can represent a challenge. Additional diagnostic difficulty is the differentiation of melanoma and PEComa from clear cell sarcoma that is indistinguishable from melanoma based on the immunohistochemical profile. Recent studies have shown that MUM-1, a known lymphocyte marker shows positive immunostaining in nevi and melanomas, its expression in PEComas and clear cell sarcoma, however, has not been previously addressed. In this study, the authors analyzed MUM-1 expression using immunohistochemistry in PEComas (n = 8), the PEComa family members, angiomyolipomas (n = 13), and clear cell sarcomas (n = 11) and compared the staining pattern with malignant melanomas (n = 25), both primary (n = 14) and metastatic (n = 11). It was found that 92.3% of primary melanomas and 81.3% of metastatic melanomas were MUM-1 positive. In contrast, MUM-1 was only weakly positive in only 25% of PEComas and negative in all angiomyolipomas. MUM-1 expression was noted in 72.7% of clear cell sarcomas. The study demonstrated differential MUM-1 expression between PEComas and other true melanocytic tumors and suggested that the addition of MUM-1 to the usual panel of melanocyte markers could be a helpful adjunctive study to aid in the differential diagnosis between these entities.

Sirtuin 1 (SIRT1): a potential immunohistochemical marker and therapeutic target in soft tissue neoplasms with myoid differentiation

Sirtuin, silent mating-type information regulation 2 homolog Saccharomyces cerevisiae 1 (SIRT1), is a protein that has been implicated in multiple mammalian functions including cell aging, stress resistance, and differentiation. SIRT1 has also been shown to be involved in multiple tumors. In addition, new pharmacotherapies have recently been approved that target SIRT1. The purpose of this study was to use immunohistochemistry to characterize SIRT1 protein expression in human soft tissue neoplasms with the hopes of finding new diagnostic and therapeutic modalities. SIRT1 immunoreactivity was reviewed in a series of 164 soft tissue tumors including alveolar soft part sarcoma, angiomyolipoma, clear cell sarcoma, desmoid/fibromatosis, desmoplastic small round cell tumor, Ewing sarcoma, gastrointestinal stromal tumor, glomus tumor, leiomyoma, leiomyosarcoma, lipoma, liposarcoma, malignant peripheral nerve sheath tumor, nodular fasciitis, osteosarcoma, rhabdomyosarcoma, schwannoma, solitary fibrous tumor, synovial sarcoma, undifferentiated pleomorphic sarcoma, and Wilms tumor. In addition, numerous benign tissues were tested for SIRT1 reactivity. In nonneoplastic tissue, strong cytoplasmic SIRT1 reactivity was observed in all prostate stroma, smooth muscle, and striated muscle. A similar pattern of cytoplasmic SIRT1 expression was observed in soft tissue neoplasms with myoid differentiation, namely, angiomyolipoma (100%), glomus tumor (100%), leiomyoma (90%), leiomyosarcoma (76.5%), and rhabdomyosarcoma (87%). The other lesions examined were negative. Although the physiologic role of SIRT1 remains to be clarified in myoid tissues and neoplasms differentiating along these lines, this observation points to a potential role for this marker in diagnostic immunohistochemistry. Furthermore, the recent emergence of drugs capable of selectively inhibiting SIRT1 raises the possibility of a potential application for targeted therapy. Additional studies are necessary to further characterise the role of SIRT1 in myoid tissues and neoplasms.

Malignant round cell tumor of bone with EWSR1-NFATC2 gene fusion

Gene rearrangements involving the Ewing sarcoma breakpoint region 1 (EWSR1) gene are seen in a broad range of sarcomas and some nonmesenchymal neoplasms. Ewing sarcoma is molecularly defined by a fusion of the EWSR1 gene (or rarely the related FUS gene) to a member of the E26 transformation-specific (ETS) family of transcription factors, frequently the EWSR1-FLI1 fusion. More recently, EWSR1 gene fusion to non-ETS family members, including the nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 2 (NFATC2) gene, has been reported in a histological variant of Ewing sarcoma. Here, we report a malignant round cell tumor of bone with an EWSR1-NFATC2 fusion gene. This report builds upon the unusual morphological and clinical presentation of bone neoplasms containing an EWSR1-NFATC2 fusion gene.

Neurofibroma of the cervix presenting as cervical stenosis in a patient with neurofibromatosis type 1: a case report.

Neurofibromatosis type 1 is an autosomal dominant disorder characterized by the presence of cutaneous and subcutaneous neurofibromas as well as deep-seated plexiform neurofibromas. Although unusual, these lesions have been described in the gynecologic tract, including the cervix; however, when arising in this location, they are commonly asymptomatic or present with lower abdominal pain. Cervical neurofibromas presenting as cervical stenosis have not been described. Awareness by both the clinician and the pathologist of a patients history is of great help when dealing with a specimen of a patient with neurofibromatosis type 1.

Subpubic Cartilaginous Cyst--A Rare Periurethral Lesion With Implications for Surgical Approach.

CASE PRESENTATION A 62-year-old African American woman was referred for evaluation of a periurethral vaginal mass that was discovered on workup for vaginal pain. She described her vaginal pain as a sensation of constant pressure in the anterior wall of her vagina that varied in severity throughout the day and had worsened over the past months. Her pain was associated with dyspareunia, as well as bothersome storage and voiding symptoms. Additionally, she had a history of urinary incontinence that occurred with both coughing and sneezing as well as with preceding urgency. Her medical history included hypertension, sleep apnea, gastroesophageal reflux, and asthma, and her surgical history was remarkable for a total abdominal hysterectomy that was performed for uterine fibroids. She never used tobacco products and did not consume alcohol or use illicit drugs. Her three children were delivered vaginally. Family history was notable for a grandmother with uterine cancer. Review of systems was negative for gross hematuria, postvoid dribbling, and vaginal bleeding. Physical examination was remarkable for a 3 cm × 3 cm firm, round, anterior vaginal wall mass, which was tender to palpation and compressing the urethra. Fluid could not be expressed per urethra upon palpation of the mass. Her uterus and cervix were surgically absent, she did not have pelvic organ prolapse, and bimanual exam did not reveal any intrapelvic pathology. Postvoid residual urine was 200 mL, and urine analysis demonstrated 3-5 red blood cells with no pyuria. Pelvic magnetic resonance imaging (MRI) revealed a 3.0 × 2.4 × 3.2 cm bilobed complex cystic lesion suggestive of urethral diverticulum (Fig. 1), although no clear communication with the urethra could be identified. Additionally, MRI revealed a 1 cm left posterolateral bladder diverticulum. On urodynamic evaluation, she was obstructed according to the Blaivas-Groutz nomogram: her maximum detrusor pressure was 50 cm of water and her peak urinary flow was 2 mL/second. She did not demonstrate stress incontinence or detrusor overactivity.

Leiomyosarcoma of the head and neck: A 17-year single institution experience and review of the National Cancer Data Base

Leiomyosarcoma is a rare neoplasm of the head and neck. The purpose of this study was to present our single‐institution case series of head and neck leiomyosarcoma and a review of cases in the National Cancer Data Base (NCDB).

Metastatic Alveolar Soft Part Sarcoma of the Spinal Cord: A Case Report and Review of Literature

BACKGROUND Alveolar soft part sarcoma (ASPS) is a rare, malignant soft-tissue neoplasm typically seen in young adults that possesses an unusual tendency to metastasize. Metastases to the intramedullary compartment of the spinal cord, however, are exceptionally rare and have not been described in the literature. CASE DESCRIPTION We report the case of a 23-year-old woman with disseminated ASPS to the lung and brain who presented with progressive lower-extremity weakness and loss of sensation after radiation and chemotherapy. Magnetic resonance imaging revealed a 1.3-cm avidly enhancing lesion within the central thoracic spinal cord at T3. A T2-T4 laminectomy was undertaken and resulted in a gross total resection. Histopathologically, the mass was composed of organoid nests containing epithelioid cells with eosinophilic, granular cytoplasm separated by sinusoidal spaces. Immunohistochemistry demonstrated convincing positive TFE3 staining. Postoperative imaging confirmed the complete resection of the mass, and her examination was notable for intact sensation and impaired motor function that gradually improved. CONCLUSIONS A review of the literature found that the reported case represents the first instance of primary or metastatic ASPS in the spinal cord. Metastatic ASPS should thus be included in the differential diagnosis in patients with known disease and neurologic impairment or back pain. Imaging of the spine should then be considered.