Pseudolymphomatous cutaneous angiosarcoma: a rare variant of cutaneous angiosarcoma readily mistaken for cutaneous lymphoma

Cutaneous angiosarcoma is probably the most malignant neoplasm involving the skin. Three clinical variants of cutaneous angiosarcoma are recognized, including angiosarcoma of the scalp and face of elderly patients, angiosarcoma associated with chronic lymphedema, and postirradiation angiosarcoma. Histopathologically, these three variants of angiosarcoma show similar features, which consist of poorly circumscribed, irregularly dilated, and anastomosing vascular channels lined by prominent endothelial cells that dissect through the dermis. Focally, neoplastic endothelial cells show large, hyperchromatic, and pleomorphic nuclei, protruding within vascular lumina and creating small papillations. Usually, inflammatory infiltrate is sparse and consists of a patchy, perivascular lymphoid infiltrate around the neoformed vessels. In rare instances, cutaneous angiosarcomas may exhibit prominent inflammatory infiltrate, and the neoplasm may be mistaken for an inflammatory process, both from clinical and histopathologic points of view. We describe four examples of cutaneous angiosarcomas with dense lymphocytic infiltrates involving the neoplasm. Immunohistochemically, lymphocytes expressed immunoreactivity for CD3, CD5, and CD45 markers, whereas the germinal centers were positive for CD20, CD79a, and Bcl-6. The neoplastic endothelial cells expressed immunoreactivity for the CD31, CD34, podoplanin, Prox-1, Lyve-1, and D2-40. We discuss the possible relationship between neoplastic endothelial lymphatic cells and reactive lymphocytes. Cutaneous angiosarcoma with prominent lymphocytic infiltrate may be readily mistaken for cutaneous follicle center cell lymphoma or cutaneous pseudolymphoma.     

Pseudolymphomatous cutaneous angiosarcoma: a report of 2 new cases arising in an unusual setting

Pseudolymphomatous cutaneous angiosarcoma represents a rare, relatively new variant of cutaneous angiosarcoma exhibiting a prominent inflammatory lymphoid infiltrate that can mask the underlying vascular malignant proliferation and mimic a lymphomatous or pseudolymphomatous process. We describe the clinicopathologic characteristics of two new cases of pseudolymphomatous cutaneous angiosarcoma whose originality lies in the unusual setting from which they have arisen. In fact, the first case was an exceedingly lymphocyte‐rich recurrence of a typical epithelioid cutaneous angiosarcoma whose primary lesion that was almost devoid of inflammatory infiltrate underwent surgical excision and radiotherapy while the second one was an unexpected histopathological finding associated with a basal cell carcinoma. Immunohistochemically, most of the lymphocytes expressed immunoreactivity for T‐cell markers, while the neoplastic endothelial lymphatic cells expressed CD31 and CD34. D2‐40 immunoreactivity was observed lining some channels and some neoplastic cells. In the first case a possible relationship between radiotherapy and the pseudolymphomatous reactive pattern is discussed while the second case has been considered as a rare example of collision tumor.     

Glomeruloid hemangioma in POEMS syndrome shows two different immunophenotypic endothelial cells

The case of a Japanese woman with glomeruloid hemangioma, an initial marker for POEMS syndrome, is reported. Her cutaneous lesions were multiple and consisted of glomeruloid hemangiomas, cherry-type capillary hemangiomas, and a mixture of both. The specimens of glomeruloid hemangiomas were studied by paraffin section immunohistochemistry with a large panel of antibodies and electron microscopy, respectively. The lesions, whose size ranged from minute foci to large nodules, were composed of anastomosing vascular channels resembling renal glomeruli and had irregular lumina, often featuring capillaries and sinusoid-like spaces. The vascular channels were lined by a single layer of endothelial cells, which showed two types of cells. The capillary-type endothelium possessed large vesicular nuclei with open chromatin and large amount of cytoplasm. The sinusoidal endothelium possessed small basal nuclei with dense chromatin as well as scant amount of cytoplasm. The former cells had a characteristic CD31+/CD34+/UEA I+/CD68- phenotype. Some of these cells ultrastructurally showed intracytoplasmic lumen formation. The latter cells had a characteristic CD31+/CD34-/UEA I-/CD68+ phenotype. The present study shows that glomeruloid hemangioma has unique morphologic and immunologic features that differ from the traditional hemangiomas as well as littoral cell angioma of the spleen.     

CD31 immunoreactivity in mesenchymal neoplasms of the skin and subcutis:

CD31 has recently been reported as a specific marker of endothelial differentiation among non-hematopoietic human neoplasms. In order to address this contention in particular regard to tumors of the skin and subcutis, the authors undertook a comparative study that surveyed 145 mesenchymal lesions. The antibodies used were directed against CD31 (clone JC/70A) and CD34 (clone My 10), and these were compared with binding of Ulex europaeus I agglutinin (UEA). Proliferations that were included in the category of vascular tumors included cavernous and capillary hemangiomas (17 cases); lymphangiomas (8); epithelioid (“histiocytoid”) hemangiomas (3), papillary endovascular hemangioendothelioma (1), angiosarcoma (7), and Kaposi's sarcoma of the mixed angiomatoid and spindle-cell type (17). CD31-immunoreactivity was observed in 35 of 53 vascular lesions; the neoplastic cells in a single angiosarcoma and the spindle cells in each case of Kaposi's sarcoma (KS) were not labeled. In all of the latter tumors, however, staining for CD31 was identified in the endothelia of angiomatoid areas and non-neoplastic blood vessels. These results compared favorably with those' seen with anti-(T).9H, which decorated 36 of 53 vascular tumors - including S of 17 KS cases - and UEA, which bound to the neoplastic cells of 36 lesions. In contrast, all of 92 non-endothelial tumors included in ibis study (34 nerve sheath tumors [30 benign; 4 malignant]; 39 fibrohistiocytic neoplasms 11 benign; 28 malignant]; 9 smooth muscle tumors [6 benign; 3 malignant]; 7 glomus tumors; and 3 giant cell fibroblastomas) were negative for CD31. UEA labeled 3 non-vascular neoplasms, whereas 38 lesions of that type were CD34-positive. The latter proliferations were benign peripheral nerve sheath tumors, examples of dermatofibrosarcoma protuberans, or glomus tumors. Based on these results, it is concluded that CD31 is a relatively sensitive and specific marker for vascular lesions and that, it is worthy of inclusion in diagnostic antibody panels which are designed to separate endothelial tumors from other neoplasms of the skin.     

Granular cell cutaneous epithelioid angiomatous nodule

Cutaneous epithelioid angiomatous nodule is an uncommon vascular lesion usually described as composed of epithelioid endothelial cells with vesicular nuclei and eosinophilic cytoplasm. A granular cell variant has not been previously described. Endothelial cells can present with granular cytoplasm as documented with reports of granular cell angiosarcoma. The granularity is thought to be due to increased intracytoplasmic lysosomes. We present a case of a benign superficial vascular lesion composed of a sheet‐like proliferation of epithelioid endothelial cells with distinctly granular cytoplasm confirmed as of endothelial origin with positive staining for CD31 and ERG.     

Macrophage-rich epithelioid angiosarcoma mimicking malignant melanoma

BACKGROUND: Cutaneous epithelioid angiosarcoma is a type of cutaneous angiosarcoma and usually arise both on the head or neck of the elderly. CASE REPORT: An 86-year-old male with an epithelioid angiosarcoma of the scalp that mimicked malignant melanoma. RESULTS: A large irregular dark grey-blue plaque with an adjacent speckled tan nodule was suggestive of a primary cutaneous malignant melanoma with adjacent in-transit metastasis. Both had a well-circumscribed growth pattern and were composed of numerous large epithelioid cells with scattered severe atypia and mitoses. The tumor was positive for S-100 protein and vimentin and negative for low- and high-molecular weight cytokeratins. However, at high power, the epithelioid cells with severe atypia were negative for S-100 protein, and abundant large epithelioid macrophages were responsible for the S-100 protein positivity. The malignant tumor cells were negative for HMB-45, positive for CD31 and Factor VIII-related antigen, and focally positive for CD34. A focus of infiltrative, classical angiosarcoma with irregular vascular channels lined with plump, anaplastic endothelial cells was then found deep to the epithelioid tumor. CONCLUSIONS: Macrophage-rich epithelioid angiosarcoma demonstrates abundant S-100 protein-positive epithelioid macrophages. This subset of epithelioid angiosarcoma may mimic malignant melanoma and may present as a pitfall in diagnosis.     

Pseudoangiosarcomatous squamous cell carcinoma of skin arising adjacent to decubitus ulcers

Pseudoangiosarcomatous, or pseudovascular, squamous cell carcinoma of skin is an unusual form of acantholytic (adenoid, pseudoglandular) squamous cell carcinoma that mimics the histolopathologic appearance of angiosarcoma. We report a case of pseudoangiosarcomatous squamous cell carcinoma arising adjacent to decubitus ulcers. The histopathologic examination of a wedge biopsy specimen revealed infiltrative cords of neoplastic cells that formed interanastomosing channels imitating angiosarcoma. Immunohistochemical staining was negative for the endothelial markers (CD31, CD34, and factor VIII-related antigen) and positive using cytokeratin antibodies (AE1/AE3 and 34 betaE12). Because of metastatic disease, palliative measures were undertaken and the patient died four months later. To our knowledge, our patient is the first with pseudoangiosarcomatous squamous cell carcinoma of skin developing within decubitus ulcer.     

Extravascular papillary endothelial hyperplasia of the palm masquerading as an angiosarcoma

Cutaneous extravascular papillary endothelial hyperplasia (PEH) is a rare lesion presenting as a cutaneous mass and histologically mimicking angiosarcoma. Herein, we describe a patient who presented with a palm tumor that had developed after trauma. Histologically, the lesion was ulcerated and showed proliferation of atypical epithelioid cells with nuclear enlargement and mitosis. Vascular proliferation was evident, and these were positive for CD31 and CD34, with approximately 20% positivity for MIB-1. We diagnosed this case as an extravascular papillary endothelial hyperplasia because there was no evidence of invasion into the surrounding tissue and elastica staining proved it did not have a vascular structure. To our knowledge, cutaneous extravascular PEH has not yet been reported in the published work.     

头面部血管肉瘤1例

患者男,80岁。头面部出现簇集血疱样皮疹40d。皮损组织病理:可见不规则的血管腔,管腔由内皮细胞排列而成,内皮细胞异型性。免疫组化检查:CD31,CD34,Vimetin(+)。诊断:头面部血管肉瘤。     

Hobnail hemangiomas (targetoid hemosiderotic hemangiomas) are true lymphangiomas

BACKGROUND: Hobnail hemangioma (targetoid hemosiderotic hemangioma) is a small benign vascular tumor of the superficial and mid-dermis. In contrast to its well-characterized histology, it has been unclear whether this tumor arises from blood vessel endothelial cells (BECs) or lymphatic vessel endothelial cells (LECs). METHODS: We analyzed 10 hobnail hemangiomas by immunohistochemistry, using the recently described lymphatic endothelial cell marker, D2-40. For comparison, CD31, CD34, and alpha-smooth muscle actin expression were studied in consecutive sections of the paraffin-embedded tissues. RESULTS: In all analyzed vessels, D2-40 labeled exclusively LECs, whereas BECs were consistently negative. In contrast to capillary BECs, either neighboring the tumors or intermingled, neoplastic endothelial cells of all 10 hobnail hemangiomas were strongly labeled by D2-40. CONCLUSIONS: The results suggest a lymphatic origin for hobnail hemangiomas. This view is further supported by the CD34 negativity of endothelial cells and the lack of actin-labeled pericytes in hobnail hemangiomas, both characteristic of lymphatic vessels. Moreover, our analysis revealed that microshunts between neoplastic lymphatic vascular channels and small blood vessels occur, explaining some features of hobnail hemangiomas, such as aneurysmatic microstructures, erythrocytes within and beneath neoplastic vascular spaces, inflammatory changes, scarring, and interstitial hemosiderin deposits.     

Benign lymphangioendothelioma presenting as a giant flank mass

Benign lymphangioendothelioma is a rare lesion of controversial etiology and a histopathologic mimic of Kaposi sarcoma and so‐called ‘well‐differentiated’ angiosarcoma. Its most typical clinical presentation is as a slowly expanding, erythematous patch or plaque; it rarely presents as a large mass. We report the second case of a giant benign lymphangioendothelioma, which arose as a serpiginous mass involving most of the flank of an elderly male with no prior radiation exposure and with a remote history of herpes zoster infection. A biopsy revealed numerous anastomosing vascular channels extending from the superficial dermis to the subcutis that were dilated to progressively slit‐like in architecture. The endothelial cells lacked cytologic atypia, hobnailing, or significant mitotic activity, and human herpesvirus‐8 expression was absent. Positivity for podoplanin (D2‐40) was observed in the endothelial cells, supporting a lymphatic phenotype. Furthermore, the lesional cells lacked immunohistochemical expression of Wilms tumor 1, providing further support of a malformative – rather than neoplastic – pathogenesis.     

Ulcerated epithelioid hemangioendothelioma of the foot in childhood

Epithelioid hemangioendothelioma is an uncommon malignant vascular tumor usually involving soft tissue and, in rare cases, the skin. Histologically and biologically it is considered to be a borderline neoplasm between an angiolymphoid hyperplasia with eosinophilia and an epithelioid angiosarcoma. Here we describe an 11-year-old girl with a 1-year history of an isolated, spontaneously appearing, painful ulceration on the instep of the right foot. The histopathologic examination of a wedge biopsy specimen revealed epithelioid eosinophilic cells with intracytoplasmic vacuoles containing erythrocytes. Immunohistochemical staining was positive for the endothelial markers CD31, CD34, and factor VIII. On the basis of these findings the diagnosis of epithelioid hemangioendothelioma was made. Two weeks after complete excision of the tumor, a lymph node metastasis in the right groin was excised. Because of another inoperable lymph node metastasis on the proximal right femur, polychemotherapy was started. As our case report shows, in the event of a nonhealing cutaneous ulceration the possibility of a malignant tumor such as epithelioid hemangioendothelioma should be considered, even in children.     

Retiform hemangioendotheliomas usually do not express D2-40 and VEGFR-3

Retiform hemangioendothelioma (RH) is a rare vascular neoplasm most often occurring in the limbs of middle-aged females. This entity is characterized by infiltrative vascular spaces arranged in a pattern similar to the rete testis. RH differs from angiosarcoma by lacking cytologic atypia and high mitotic rates. This neoplasm frequently recurs but rarely metastasizes. RH tumor cells react with vascular endothelial markers CD31, CD34, and factor VIII-related antigen. A review of the English literature provides only one attempt at staining RH with D2-40, a marker of endothelium of lymphatic vessels, which was negative, and one reported staining of RH with lymphatic endothelial marker VEGFR-3, which was positive. The etiology of RH is unknown. RH has previously been considered closely related to Dabska tumors, which are positive for lymphatic endothelial marker D2-40. We stained 4 RHs with mouse monoclonal antibodies against D2-40 and CD31 and 3 of the 4 RHs with vascular endothelial growth factor receptor 3 (VEGFR-3), to further evaluate whether RH had lymphatic differentiation, in addition to vascular differentiation. Three of the 4 RH biopsies failed to demonstrate D2-40, none expressed VEGFR-3, whereas CD31 was strongly positive, suggesting that RH is a vascular entity which usually does not have lymphatic differentiation, but may rarely express D2-40.     

Granulocyte colony-stimulating factor-producing cutaneous angiosarcoma with leukaemoid reaction arising on a burn scar

We report a 46-year-old man with a giant tumour in a burn scar on his buttock. Pathological examination revealed that the dermis was filled with anastomosing vascular channels and round- or spindle-type atypical cells, which were compatible with the diagnosis of cutaneous angiosarcoma. Based on prominent leucocytosis (up to 113 000 microL-1), we measured serum granulocyte colony-stimulating factor (G-CSF). The highly elevated serum G-CSF of 303 ng L-1 (normal, 6.1-21.5 ng L-1) and positive immunohistochemical staining of the tumour tissue for G-CSF indicated that G-CSF was produced by the cutaneous angiosarcoma. To our knowledge, this is the first reported case of G-CSF-producing cutaneous angiosarcoma.     

皮肤颗粒细胞瘤1例及文献复习

患者女,56岁。发现左耳后质硬结节5月就诊。皮肤组织病理示:真皮层可见排列成巢状或束状的肿瘤组织,瘤细胞为多角形,胞浆丰富,淡粉染,充满嗜酸性颗粒。免疫组化标记CD34,CD68,S-100,Vimentin(+)。诊断:皮肤颗粒细胞瘤。治疗:采取完全手术切除。     

Multifocal congenital lymphangioendotheliomatosis without gastrointestinal bleeding and/or thrombocytopenia

A 5-month-old male infant presented with an increasing number of widespread asymptomatic violaceous cutaneous macules, papules, and nodules since birth. He is 1 of the 2 identical twins born to unrelated healthy parents. Histology revealed proliferation of dilated thin-walled vascular channels lined by bland endothelial cells in the dermis and subcutis. In some of the vascular channels, there were formations of intravascular papillae surrounded by hobnail endothelial cells. Immunohistochemistry demonstrated positive staining for CD31, CD34 factor VIII and vascular endothelial growth factor-3 (VEGFR-3) and negative staining for D2-40 and latencyassociated nuclear antigen-1 (LANA-1). The clinical and histologic findings were compatible with multifocal congenital lymphangioendothelionmatosis with thrombocytopenia, except that a year of follow-up was uneventful and no gastrointestinal bleeding or thrombocytopenia was recorded.     

Cutaneous epithelioid hemangioendothelioma

Epithelioid hemangioendothelioma is a rare vascular tumor of intermediate aggressiveness, which usually appears in adults. It generally affects soft tissues and, less frequently, the lungs and liver. Diagnosis is by histological evaluation, and the epithelioid appearance of the neoplastic endothelial cells is typical, as is the tendency to form vascular channels. Treatment is surgical excision, with broad margins. This tumor may in exceptional cases affect the skin, with few cases having been described in literature. We describe the case of a male patient with plantar epithelioid hemangioendothelioma, and we review the literature.     

Angiosarcoma with pseudoepidermotropism in a patient with breast cancer: a mimic of epidermotropic metastatic adenocarcinoma

We report a case of cutaneous postradiation angiosarcoma of the breast exhibiting pseudoepidermotropism that resembled metastatic adenocarcinoma on hematoxylin and eosin. The patient is a 74-year-old woman with history of breast carcinoma treated with mastectomy, chemotherapy, and radiotherapy who complained of an erythematous "rash" along the central portion of the mastectomy scar. Radiography showed widespread osseous metastasis. Biopsy revealed an infiltrative tumor with single file growth and tumor cells obscuring the dermal--epidermal junction in multiple foci, imparting an appearance of epidermotropism. The tumor cells were positive for CD31, CD34, and D2-40 and negative for Cam 5.2. This novel case of pseudoepidermotropic angiosarcoma highlights a potential pitfall in the histomorphologic assessment of poorly differentiated angiosarcoma.     

Cardiac epithelioid angiosarcoma presenting as cutaneous metastases

BACKGROUND: Cardiac angiosarcoma is a rare tumor that has a predilection for middle-aged males and a marked predominance in the right atrium. The tumor may present abruptly with a fulminant clinical course. Initial presentation with metastatic disease is rare. Only one case has been reported of a patient who presented with cutaneous metastases. METHODS AND RESULTS: We here report the case of a 51-year-old man who initially presented with cutaneous metastases in the absence of cardiac symptoms. The skin biopsy was diagnosed as metastatic undifferentiated sarcoma. The patient died 26 days later with widely disseminated disease. At autopsy a tumor arising in the wall of the left atrium and in the interatrial septum was found. After an immunohistochemical study including CD31 and CD34 stains the diagnosis of cardiac pure epithelioid angiosarcoma was made. To the best of our knowledge this tumor variant has not been documented in the heart until now. CONCLUSION: Although cardiac angiosarcoma is a rare neoplasm, its presence should be suspected in patients with cutaneous metastatic angiosarcoma without an evident source of the tumor, even in absence of cardiac symptoms.     

Superinfected cutaneous angiosarcoma: a highly malignant neoplasm simulating an inflammatory process

This report describes a patient with a poorly differentiated cutaneous angiosarcoma (CA) of the face superinfected with pseudomonas aeruginosa. Neoplastic cells were positive for CD-34, CD-31 and vimentin, whereas they failed to express other vascular markers such as Factor VIII and Ulex europeaus lectin. The tumor spread rapidly through the skin and the superficial soft tissue before metastasizing. The patient died of disease 6 months after histopathological diagnosis. An autopsy revealed widespread metastases in the lung and the liver. The aim of this report is to call attention to some circumstances in which CA may masquerade as an inflammatory process, delaying the right diagnosis with serious consequences for the patient.