Diagnostically Challenging Epithelioid Vascular Tumors

The diagnosis of vascular tumors is a challenging area in soft tissue pathology. Epithelioid vascular tumors pose a particular challenge. Due to the epithelioid morphology of the tumor cells, they can be misdiagnosed as a variety of other entities, including metastatic carcinoma or epithelioid sarcoma. Furthermore, it can be difficult to distinguish between different epithelioid vascular tumors. This review focuses on vascular tumors characterized by epithelioid endothelial cells, including epithelioid hemangioma, cutaneous epithelioid angiomatous nodule, epithelioid hemangioendothelioma, epithelioid sarcomalike hemangioendothelioma/pseudomyogenic hemangioendothelioma, and epithelioid angiosarcoma.     

Hepatic malignant epithelioid hemangioendothelioma: a case report and review of the literature

Malignant epithelioid hemangioendothelioma is a rare hepatic tumor of vascular origin. It is most commonly found in young to middle aged women, and the tumors vary in reported malignant potential. Compounds such as oral contraceptive pills, poly vinyl chloride, and Thorotrast have been identified as risk factors for subsequent disease development. Radiologic ("lollipop" sign, capsular flattening) and pathologic (Factor-VIII antigen staining positive) evaluation aids in the diagnosis. As with most mesenchymal tumors, surgical resection is the most effective means of controlling local disease and preventing distant metastasis, though adjuvant therapies have been offered for those that are unresectable or not transplant candidates. We present our case of a hepatic malignant epithelioid hemangioendothelioma and a review of the English-language literature.     

Primary High-Grade Poorly Differentiated Angiosarcoma of an Intra-parotid Lymph Node

Head and neck angiosarcoma is an infrequent malignant vascular tumor most commonly found in the skin and soft tissue of the head and neck. Most head and neck angiosarcomas are metastatic to cervical lymph nodes from other primitive location. We describe herein a case of primary high-grade poorly differentiated angiosarcoma arising in an intra-parotid lymph node, discuss the value of immunohistochemical stains for differential diagnosis, and review the literature concerning head and neck angiosarcoma. A 47-year-old man presented with a painless mass that had grown for a period of 6 months in the parotid area. The CT-scan revealed a left parotid lesion of 17 mm. Fine needle aspiration was considered suspicious for lymphoma or poorly differentiated carcinoma. A superficial parotidectomy was performed. On gross examination, the lesion was a well-defined, gray, homogeneous mass of 15 mm of diameter. Microscopic examination showed a normal parotid tissue and a poorly differentiated malignant neoplasm in an intra-parotid lymph node. The tumor had a pseudo-alveolar pattern, with large pleomorphic epithelioid cells, abundant eosinophilic cytoplasm, large vesicular nuclei, and one or more prominent nucleoli. Atypical mitoses were seen. Neoplastic malignant cells stained positive for Vimentin, CD31, D2-40, factor VIII, ERG, and partially for CD34. A positron emission tomography scan was made to search for a primary neoplasia, but no other tumor was localized. The diagnosis of primary high-grade, poorly differentiated, intra-parotid lymph node angiosarcoma was established.     

Lymph node metastases in differentiated thyroid cancer under 2 cm

BACKGROUND: The goal of this study was to evaluate the presence of lymph node metastasis in patients with T1 differentiated thyroid cancer (DTC) and determine prognostic significance for tumor recurrence and cancer-related death. METHODS: From a prospective tumor registry, we reviewed data from 551 patients with DTC who underwent total or subtotal thyroidectomy and who had primary tumor size 相似文献   

Epithelioid hemangioendothelioma of the brain.

Epithelioid hemangioendothelioma is a recently described vascular neoplasm characterized by epithelioid tumor cells and borderline biologic behavior. Its four principal sites of occurrence are the soft tissue, liver, lung, and bone. We report a case of primary cerebral epithelioid hemangioendothelioma in a 4-month-old male infant. The tumor consisted of loose aggregates of epithelioid cells with a focal cordlike or bridging-branching pattern, supported in a fibromyxoid stroma. The tumor cells displayed frequent intracytoplasmic vacuoles. Immunohistochemically, the tumor cells showed positive staining for Ulex europaeus agglutinin, vimentin, and cytokeratin. The tumor pursued an indolent clinical course. The patient was alive 28 months after initial presentation, but he was left with a severe neurological deficit because of the location and growth of the tumor.     

Epithelioid hemangioendothelioma of the oral cavity: report of two cases and review of the literature.

The epithelioid hemangioendothelioma is an uncommon vascular neoplasm of borderline or intermediate malignant potential. Although numerous sites of involvement are possible, these tumors most commonly arise in soft tissue, liver, and lung. Involvement of the oral cavity is rare. Only 12 cases of intraoral epithelioid hemangioendothelioma have been reported in the English language literature. We review the salient features of these previously reported cases and present 2 additional intraoral cases--one presenting as an asymptomatic radiolucency in the posterior mandible of a 23-year-old female, and the other presenting as an asymptomatic, erythematous to purplish gingival nodule in a 28-year-old female. Intraoral tumors most commonly involve the gingival soft tissues and often are associated with adjacent alveolar bone resorption. Although it is not possible to estimate with accuracy the potential for recurrence and metastasis among intraoral tumors given the small number of previously reported cases, wide local excision with close clinical follow-up appears to be the treatment of choice for these tumors because of their unpredictable clinical behavior.     

Malignant epithelioid hemangioendothelioma of the liver in young women. Relationship to oral contraceptive use

Epithelioid hemangioendothelioma (EH) is a vascular neoplasm that occurs predominantly in soft tissue and is not infrequently misdiagnosed as an epithelial neoplasm or angiosarcoma. Only a few cases of hepatic EH have been described, and a relationship to oral contraceptive (OC) use in patients with the hepatic lesions has not generally been recognized. We present a series of five patients with malignant epithelioid hemangioendothelioma of the liver. Confirmation of the endothelial origin of these tumors was provided by positive immunoperoxidase staining for Factor-VIII-related antigen in the four cases studied by that technique, and by the demonstration of Weibel-Palade bodies in two tumors examined by electron microscopy. All five patients were young women (mean age 33 years) and all five gave a history of OC use of 4-7 years' duration. The clinical course varied from indolent but progressive to rapid death. One patient who underwent resection of the primary tumor has survived 3 years without evidence of disease, and one patient with metastatic disease who was treated with radiation and chemotherapy has survived for 8 years with disease. Three patients with extrahepatic spread have died of the tumor. Early diagnosis of this distinctive tumor might offer the hope of salvage by resection or liver transplantation.     

Composite Hemangioendothelioma of the Submandibular Region

Composite hemangioendothelioma (HE) is a rare vascular neoplasm of intermediate malignant potential that predominantly occurs within the dermis or subcutis of the extremities, and occurs in a wide age range. It is locally aggressive with a high rate of local recurrence, and more rarely regional lymph node or distant metastasis. Histologically, it is composed of a complex admixture of benign, intermediate and malignant vascular components. Although composite HE may contain angiosarcoma-like areas, its prognosis is better than that of pure angiosarcoma. We describe a case of composite HE presenting as a submandibular mass in a 43 year-old male, which included areas of prominent ‘high grade’ epithelioid angiosarcoma. This adds to the range of anatomic sites of these neoplasms, highlights the importance of recognition of the head and neck as a potential site, and emphasizes the importance of accurate diagnosis for correct management (including of long term follow up) and prognostication.     

Epithelioid sarcoma-like hemangioendothelioma

We are reporting seven histologically identical cases of a distinctive, low-grade vascular tumor that closely mimics an epithelioid sarcoma because of growth in solid sheets and nests, the eosinophilia of the rounded to slightly spindled neoplastic cells, and the diffuse, strong cytokeratin expression. Termed epithelioid sarcoma-like hemangioendothelioma, all were diagnosed by the submitting pathologist or another expert consultant as epithelioid sarcoma. Although none displayed architectural evidence of vascular differentiation in the form of multicellular vascular channels, some displayed subtle cytologic features of vascular differentiation and all displayed immunohistochemical evidence of endothelial differentiation. The patients (four male; three female) ranged in age from 17 to 54 years (median 23 years). Ranging in size from 1 to 3.5 cm, they occurred in the extremities (n = 5), scalp (n = 1), and chest wall (n = 1), both in deep (n = 3) and superficial (n = 3) soft tissue or both (n = 1). The tumors were characterized by sheets, ill-defined nodules, or fascicles of deeply eosinophilic cells set within a desmoplastic stroma. Multicellular vascular channel formation and/or hemorrhage were absent in all cases. In four cases intracytoplasmic vacuolization suggestive of intracytoplasmic vascular lumen formation was noted. The typical neoplastic cell was large and rounded in shape but modulated in areas to a spindled or multipolar shape. Mitotic activity was low (<5 mitotic figures/50 high power fields), nuclear pleomorphism was mild to moderate, and necrosis was absent. The tumors were positive for cytokeratin (6 of 6), vimentin (6 of 6), CD31 (5 of 6), FLI-1 (6 of 6), but negative for CD34 (0 of 6). Within a follow-up period of 3-72 months (median 39 months), two patients experienced a local recurrence and one patient regional soft tissue metastases, but no distant ones. Two patients presented with multifocal lesions suggestive of regional metastases. Currently, two patients are alive with disease and five are disease free. Epithelioid sarcoma-like hemangioendothelioma appears to be a largely unrecognized epithelioid vascular tumor with an indolent course. Despite its similar clinical and histologic features, it differs from epithelioid sarcoma by the presence of endothelial markers and the absence to date of distant metastases. Its distinction from other epithelioid vascular lesions is discussed. We think this tumor fits best into the family of "hemangioendothelioma" or vascular lesions of intermediate malignancy.     

Ultrasound B-scans in the follow-up of head and neck tumors

In recent years, diagnostic ultrasound has become established in head and neck surgery. Modern equipment allows high resolution imaging of neck tissue masses, cervical vessels, and lymph nodes. The major advantage of B-mode sonography is its ability to detect neoplasms in solid scarred neck tissue, commonly seen in patients with radical neck surgery. Postoperative or radiogenic edema, tumor recurrence, and lymph node involvement can be differentiated. Inflammatory and neoplastic lymph node diseases detected by echography must be differentiated by biopsy. Tumor recurrence was seen in 21 of 152 patients by echography. Twelve patients were diagnosed by clinical examination and 17 were diagnosed by computed tomography. Two false positive and one false negative sonographic diagnoses were made. B-mode sonography is an important instrument in the follow-up examination of head and neck tumors for early detection of tumor recurrence or tumor persistence.     

Primary vascular tumors of lymph nodes other than Kaposi's sarcoma. Analysis of 39 cases and delineation of two new entities.

Primary vascular tumors of lymph nodes other than Kaposi's sarcoma are very rare, as attested to by only a handful of case reports in the literature. Based on an analysis of 39 such cases, we could distinguish five major groups. Hemangiomas of capillary/cavernous, lobular capillary, and cellular types were composed of compact aggregates of blood-filled vessels, variable in size, that replaced the nodal architecture partly or almost completely; some appeared to have originated in the hilum or medulla. These hemangiomas either represented incidental findings in lymph nodes or were seen with solitary lymph node enlargement; the evolution was benign with no recurrence. A distinctive benign lesion occurring exclusively in inguinal lymph nodes, which we propose designating "angiomyomatous hamartoma," showed replacement of the nodal parenchyma by smooth muscle cells and fibrous tissue, in continuity with exuberant proliferation of muscular vessels in the hilum. Epithelioid vascular tumors, characterized by plump endothelial cells with dense eosinophilic cytoplasm and numerous vacuoles, exhibited a range of differentiation, from hemangioma with well-formed vascular channels (with or without tissue eosinophilia) to hemangioendotheliomas composed predominantly of cords and sheets of tumor cells lying in a hyaline-myxoid matrix. Epithelioid hemangioendothelioma was particularly likely to be mistaken for metastatic carcinoma, and local recurrence could occur. A variant, the spindle and epithelioid hemangioendothelioma, was characterized by the presence of an additional component of spindle cells. Another tumor we found, polymorphous hemangioendothelioma, is a previously uncharacterized borderline malignant vascular tumor exhibiting solid, primitive vascular and angiomatous patterns and relatively bland cytologic features. Lymphangiomas of lymph nodes usually showed simultaneous multifocal and extra-nodal involvement and were characterized by cystic endothelium-lined spaces filled predominantly with lymph fluid. It is important to recognize these primary vascular tumors of lymph nodes to avoid mistaking them for a variety of benign vasoproliferative lesions, Kaposi's sarcoma, angiosarcoma, and metastatic cancer.     

Pseudomyogenic hemangioendothelioma: a distinctive, often multicentric tumor with indolent behavior

A 1992 report described 5 keratin-positive spindle cell neoplasms with multifocal presentation in a single limb, which were proposed at that time to be a variant of epithelioid sarcoma. This tumor type is not widely recognized and is incompletely characterized. We examined 50 cases of this distinctive tumor to evaluate histologic, immunophenotypic, and clinical features. There was a 4.6:1 male predominance (mean age, 31 y; 82% ≤40 y). Half of the patients presented with painful nodules and the other half with painless nodules. Mean tumor size was 1.9 cm (range, 0.3 to 5.5 cm). Tumors arose in the lower limb (54%), the upper limb (24%), trunk (18%), or head and neck (4%). Thirty-three (66%) were multifocal lesions (ranging from 2 to 15 lesions), including 32 cases with involvement of multiple tissue planes. Of 205 total lesions, 64 (31%) involved the dermis, 42 (20%) involved the subcutis, 70 (34%) lesions involved muscle, and 29 (14%) lesions involved bone; all the lesions had infiltrative margins. The tumors were composed of loose fascicles and sheets of plump spindle cells with vesicular nuclei, variably prominent nucleoli, and abundant brightly eosinophilic cytoplasm, some with a strikingly rhabdomyoblast-like appearance. In all cases, a minority of cells were epithelioid. Twenty-seven tumors contained a prominent neutrophilic inflammatory infiltrate. Most tumors showed only mild nuclear atypia; 6 tumors contained foci of notably pleomorphic cells. The median mitotic rate was 1 per 10 HPF (range, 1 to 10). Seven tumors showed vascular invasion; 7 tumors had areas of necrosis. By immunohistochemistry, all tumors were diffusely positive for AE1/AE3 and FLI1; 22 of 47 tumors were variably positive for CD31. Focal positivity was seen for CAM5.2 (21 of 35), smooth muscle actin (14 of 42), epithelial membrane antigen (7 of 49 weak), and PAN-K (MNF116) (1 of 47). All were negative for CD34, desmin, and S100 protein and showed intact INI1 expression. Follow-up was available for 31 patients and ranged from 9 months to 17 years (mean, 4 y). Most lesions were treated by local excision. Eighteen (58%) patients had local recurrence or developed additional nodules in the same region, all but one, within 1 year of first presentation. Eight patients had postoperative radiation therapy and 6 patients had chemotherapy. Four patients had amputations for multifocal disease. One patient had a regional lymph node metastasis, and, thus far, only 1 patient has developed distant metastases (disseminated), 16 years after primary tumor excision. At the time of the last follow-up, 27 patients were alive with no evidence of the disease, 1 patient was alive with unknown disease status, 2 patients were alive with recurrent disease, and 1 patient died of the disease. In summary, we describe a distinctive type of rarely metastasizing ("intermediate") tumor affecting mainly young men and usually characterized by multifocality in different tissue planes of a limb. Although sharing some features with epithelioid sarcoma (skin/soft tissue of distal extremities, young adults, keratin positive), it differs by having predominantly myoid-appearing spindle cell morphology, expression of FLI1, common reactivity for CD31, lack of epithelial membrane antigen, CD34, and PAN-K expression, and intact INI1. The overall immunophenotypic findings favor endothelial differentiation. Despite the ominous presentation, follow-up thus far suggests an indolent clinical course with a small risk of distant metastasis. Although the precise nosologic status of this tumor type is uncertain, we propose the interim designation "pseudomyogenic hemangioendothelioma."     

Primary epithelioid hemangioendothelioma of the retroperitoneum: report of a case

We herein report the case of a 48-year-old Japanese female with retroperitoneal epithelioid hemangioendothelioma (EHE), a rare malignant vascular tumor of intermediate grade. She was referred to our hospital because a retroperitoneal tumor was found during a medical checkup, in which strong accumulation of (18)F-fluorodeoxyglucose (FDG) was observed by (18)F-FDG-positron emission tomography (PET). A histological examination of the resected tumor revealed that it consisted of large epithelioid cells with vesicular nuclei, and clear cells with vacuolated cytoplasm and intracytoplasmic lumina. These cells expressed CD31 and vimentin, and the final pathological diagnosis was EHE. Postoperative surveillance with FDG-PET revealed distant metastasis in Virchow's lymph node 7?months after the operation. After dissection of the metastatic lymph node, the patient has been free from recurrence for 13?months. Close follow-up with FDG-PET seemed to be useful for surveillance of the recurrence of this tumor with unpredictable behavior, making an early treatment for the recurrent lesions possible.     

肝上皮样血管内皮瘤1例并文献复习

目的提高对肝上皮样血管内皮瘤的认识。方法结合我院诊治的一例肝上皮样血管内皮瘤的患者资料和文献复习,探讨该病的临床特点、诊断、治疗及预后等。结果肝上皮样血管内皮瘤病因尚不明确,最常见的临床表现是右上腹疼痛、肝肿大和体重减轻,MRI或CT特点为:病灶对比增强扫描大于3 cm的病灶增强后有向心性强化倾向,而小于3 cm的病灶呈环形强化,门脉期及延迟期持续环形强化,肝内静脉主干及分支终止于肿瘤的边缘,形成"棒棒糖征"。病理学检查主要特征是具有细胞内血管腔的上皮样瘤细胞并呈血管内皮标志物染色阳性。肝上皮样血管内皮瘤的治疗以手术切除和肝移植为主,预后介于良、恶性肿瘤之间。结论肝上皮样血管内皮瘤发病率低、临床表现复杂,易误诊,临床诊治过程中应予以重视。     

Predictive value of cathepsin-D for cervical lymph node metastasis in head and neck squamous cell carcinoma

BACKGROUND: Prognosis of head and neck squamous cell carcinoma (HNSCC) is strongly associated with cervical lymph node metastasis. Cathepsin-D is a lysosomal protease expressed in all cells. Its role in extracellular matrix degradation is postulated to promote tumor invasion and metastasis. Increased cathepsin-D has been demonstrated in cervical lymph node metastasis in HNSCC. METHODS: Formalin fixed tumor biopsy samples from 34 patients with HNSCC of the oral cavity, oropharynx, or hypopharynx were analyzed for the presence of cathepsin-D by immunohistochemistry (1:8000, Calbiochem, Cambridge, MA). Tumors were considered positive if >50% of cells showed strong cytoplasmic staining. RESULTS: All patients had T1 or T2 lesions ranging in size from 1-4 cm and 19 (56%) had cervical metastasis. Eight (24%) were well differentiated and 26 (76%) were moderately or poorly differentiated. Thirteen tumors (38%) had high cathepsin-D expression that was strongly associated with cervical lymph node metastasis (p = 0.008). When adjusted for tumor stage and grade, cathepsin-D positivity was nearly twice as likely to be associated with node metastasis (p = 0.011). CONCLUSIONS: We demonstrated cathepsin-D expression in biopsies from a subset of patients with HNSCC and a strong association between this protease and cervical lymph node metastases. Cathepsin-D is a potential independent predictor of cervical lymph node metastasis in HNSCC and merits additional study.     

电压门控钠通道的表达与结直肠癌淋巴结转移的关系

背景与目的:淋巴结转移是影响结直肠癌(CRC)患者预后的关键因素.电压门控钠通道(Nav)在多种肿瘤中高表达,且与肿瘤的转移密切相关.因此,本研究探讨CRC组织中不同的Nav亚型的表达情况以及Nav的表达与CRC淋巴结转移及侵袭性的关系.方法:收集100例首发CRC患者的肿瘤组织和癌旁组织手术标本,行HE检测鉴别后,采...     

Improved methods of detection of lymphovascular invasion demonstrate that it is the predominant method of vascular invasion in breast cancer and has important clinical consequences

The presence of vascular invasion (VI), encompassing both lymphovascular invasion (LVI) and blood vascular invasion (BVI), in breast cancer has been found to be a poor prognostic factor. It is not clear, however, which type of VI plays the major role in metastasis. The aims of this study were to use an endothelial subtype specific immunohistochemical approach to distinguish between LVI and BVI by comparing the differential expression of blood vascular (CD34 and CD31) and lymphatic markers (podoplanin/D2-40) to determine their prognostic role in a well-characterized group of breast cancer patients with known long-term follow-up. Sections from 177 consecutive paraffin-embedded archival specimens of primary invasive breast cancer were stained for expression of podoplanin, D2-40, CD31, and CD34. BVI and LVI were identified and results were correlated with clinicopathologic criteria and patient survival. VI was detected in 56/177 specimens (31.6%); 54 (96.4%) were LVI and 2 (3.5%) were BVI. The presence of LVI was significantly associated with the presence of lymph node metastasis, larger tumor size, development of distant metastasis, regional recurrence and worse disease-free interval and overall survival. In multivariate analysis, LVI retained significance association with decreased disease-free interval and overall survival. In conclusion, VI in breast cancer is predominantly of lymph vessels and is a powerful independent prognostic factor, which is associated with risk of recurrence and death from the disease. The use of immunohistochemical staining with a lymphendothelial specific marker such as podoplanin/D2-40 increases the accuracy of identification of patients with tumor associated LVI.     

Role of Sentinel Lymph Node Biopsy in the Staging of Synovial, Epithelioid, and Clear Cell Sarcomas

Background  Soft tissue sarcomas generally have a ≤5% risk of lymph node metastasis, but synovial, epithelioid, and clear cell subtypes reportedly have a much higher risk. The utility of sentinel lymph node biopsy (SLNB) for patients with these sarcoma subtypes is unknown. Methods  29 patients with nonmetastatic synovial, epithelioid, and clear cell sarcomas who underwent SLNB were examined. Results  Median age was 35 years (range 11–73 years), and 69% were male. Tumors were located in the lower extremity in 17 patients and the upper extremity in 12. The histological subtypes were synovial sarcoma in 16 patients, epithelioid sarcoma in 10, and clear cell sarcoma in 3. All patients had a staging chest computed tomography (CT) scan, none of which were suspicious, and 20 patients had staging positron emission tomography (PET) scans (16 negative, 3 indeterminate, and 1 suspicious). All patients had resection of their primary tumor. At least one sentinel node was found in 28 patients (97%), and the median number of sentinel nodes identified was 2 (range 1–4). One patient had a positive sentinel node on routine hematoxylin and eosin (H&E) staining and developed lung metastases. Two patients had positive sentinel nodes following immunohistochemical staining, and both remain disease free despite not undergoing completion lymphadenectomy. One patient developed a lymph node metastasis after a negative SLNB. Conclusion  For patients with these sarcoma subtypes without radiological evidence of nodal or distant metastases, the incidence of occult lymph node metastasis is relatively low. Determining utility of SLNB may require a multicenter trial.     

Unexpected lymph node pathology in neck dissection for head and neck cancer

The pathological findings in 62 patients with head and neck cancers who underwent neck dissection during a 12-month period are presented. Histological confirmation of metastatic disease was obtained in 46 cases (74%). In the remaining 16 cases (26%), there was no evidence of metastasis from the primary tumor. In 7 cases (11%), there was unexpected pathology in the cervical lymph nodes which was not related to the primary tumor. Accurate clinical staging of head and neck tumors is made increasingly more difficult in such cases where unrelated or dual lymph node pathology exists.