Report of an angiosarcoma mimic: cutaneous aneurysmal fibrous histiocytoma

Aneurysmal fibrous histiocytoma is an unusual variant of the spectrum of fibrous histiocytomas with the peculiar morphologic appearance of a benign aneurysmal vasoformative process that ultimately culminates in multiple microhemorrhages within the tumor. It looks strikingly different from the usual cutaneous lesions encountered in clinical dermatology practice. A single report of a cutaneous aneurysmal fibrous histiocytoma in the skin of the back of a 60-year-old male is described with emphasis on the immunostaining pattern and review of the literature. There is a significant potential for confusion of this lesion with other cutaneous lesions, clinically as well as pathologically. In our case, the patient presented with a lesion that clinically resembled a hemangioma, was pathologically interpreted initially to be an angiosarcoma, and finally, the revised pathology was interpreted as an aneurysmal variant of a fibrous histiocytoma. Caution is warranted to avoid misinterpretation of cutaneous fibrohistiocytic tumors.     

Atypical fibroxanthoma of the skin: a clinicopathological and immunohistochemical study and a discussion of its histogenesis

The morphological and immunohistochemical characteristics of 37 atypical fibroxanthomas of the skin were examined. Twenty-four tumours were nodular ulcerative lesions on the head and face of patients with a median age of 75 years, whereas 13 tumours occurred on the trunk and limbs of patients with a median age of 48 years. Both pleomorphic polygonal and giant cells as well as the spindle cell component of the tumours stained for the histiocytic markers alpha 1-antichymotrypsin, alpha 1-antitrypsin, lysozyme and, less frequently, for ferritin. Leu M1 antigen and peanut agglutinin receptors were not demonstrable in tumour cells. This antigenic profile was contrasted with the findings in six cases of dermatofibroma which were largely not reactive with the antisera used. The immunohistochemical findings in atypical fibroxanthomas suggest that they represent a homogeneous group of tumours which are related to tissue histiocytes. These results are discussed in the context of the published findings in other so-called fibrohistiocytic tumours including dermatofibrosarcoma protuberans and malignant fibrous histiocytoma. The diagnoses in three cases coded as atypical fibroxanthomas were revised on the basis of their showing a different immunohistochemical profile.     

Primary cutaneous leiomyosarcoma: a histological and immunohistochemical study of 4 cases

Primary cutaneous leiomyosarcoma is an uncommon malignant neoplasm with a predilection for the lower extremities. A retrospective study of 4 cases was undertaken to analyse the clinicopathological characteristics and immunohistochemical profile of these neoplasms with emphasis on prognosis. Two male and 2 female patients aged between 49 and 80 years presented with painless tumours involving the lower lip, the chin, the scrotum and the shoulder. Histological examination of the initial biopsy specimen established a diagnosis of cutaneous leiomyosarcoma. All cases co-expressed smooth muscle actin and vimentin regardless of primary tumour site. Wide surgical excision of the tumour was performed in only 3 cases, and the remaining patient refused further treatment. Of the patients undergoing surgical intervention, local recurrence occurred in one case. No metastases were observed. Long-term follow-up of patients with cutaneous leiomyosarcoma is mandatory to detect local recurrence and distant metastases that can occur even years after the initial excision.     

Distinct histological features characterize primary angiosarcoma of bone

Verbeke S L J, Bertoni F, Bacchini P, Sciot R, Fletcher C D M, Kroon H M, Hogendoorn P C W & Bovée J V M G
(2011) Histopathology  58, 254–264
Distinct histological features characterize primary angiosarcoma of bone Aims: To define the histological criteria of primary angiosarcoma of bone. Methods and results: Forty‐two angiosarcomas of bone in 23 males and 15 females were studied. Histological criteria were related to patients’ outcome. Eleven patients had multifocal lesions. Lesions were located in the long and short tubular bones followed by the pelvis, spine and trunk. Tumour cells were positive for CD31 in 38 of 40, von Willebrand Factor in 21 of 35, CD34 in 15 of 38, smooth muscle actin in 22 of 36, D2–40 in 11 of 35 and keratinAE1AE3 in 27 of 39. Thirty‐nine tumours showed an epithelioid phenotype. One‐ and 5‐year survival rates were 55% and 33%, respectively. Survival analysis showed that a macronucleolus, three or more mitoses per 10 high‐power field (HPF) and fewer than five eosinophilic granulocytes per 10 HPF within a tumour was associated with an even worse survival compared to the overall group. Conclusions: Because keratin positivity is seen in the majority of cases, pathologists should avoid misinterpretation as metastatic carcinoma. A macronucleolus, three or more mitoses per 10 HPF and fewer than five eosinophilic granulocytes per 10 HPF can be used to further define angiosarcoma of bone.     

Primary and secondary cutaneous angiosarcoma: Distinctive clinical,pathological and molecular features

Angiosarcomas are ubiquitous neoplasms involving both cutaneous and soft tissue and visceral locations. Accumulating biomolecular evidences suggest that cutaneous angiosarcomas are distinctive entities with molecular, clinical and pathological peculiarities. Despite several ongoing clinical trials with promising therapeutic agents, the prognosis of cutaneous angiosarcomas is dismal and survival still rely on early diagnosis and surgery. An accurate diagnosis and the knowledge of the underlying molecular landscape are therefore essential to improve the prognosis. We detail the molecular, clinical, dermoscopic, morphological and prognostic features of cutaneous angiosarcoma. Although the molecular landscape of cutaneous angiosarcoma is not completely understood, accumulating evidences suggest that there are characteristic molecular alterations including dysregulation of angiogenesis and several complex molecular pathways. Secondary cutaneous angiosarcomas, arising in correlation with chronic lymphedema and ionizing radiation, have different molecular hallmarks, which are also leading to the first diagnostic applications. The diagnosis of cutaneous angiosarcoma may be challenging, as well-differentiated forms can be hard to distinguish from benign and low-grade vascular neoplasms, while poorly differentiated forms can be easily confounded with other non-vascular high-grade neoplasms. An accurate and early diagnosis, which is mandatory to ensure the best survival for the patients, is mainly based on morphological hallmarks.     

Primary epithelioid angiosarcoma of bone: a case report with immunohistochemical study

Primary malignant vascular tumors of the bone are exceedingly rare and represent <1% of primary malignant bone tumors. Angiosarcoma is a malignant mesenchymal neoplasm in which the neoplastic cells demonstrate endothelial differentiation. Epithelioid angiosarcoma (EA) is a rare variant of angiosarcoma that is characterized by large cells with an epithelioid morphology. EA is an aggressive tumor with poor prognosis. Here, we present a case of a 62-year-old man who had primary EA of the left tibia. He was treated with amputation and chemotherapy. After 1 month of chemotherapy, he developed pleural effusion and died.     

Cytological, histological, and immunohistochemical findings of pulmonary carcinomas with basaloid features

Pulmonary basaloid carcinoma (BC), a variant of large cell, nonsmall cell carcinoma (NSCC), and basaloid squamous cell carcinoma (BSQCC) can show features similar to small cell carcinoma (SCC) and large cell neuroendocrine carcinoma (LCNEC). Distinction from SCC, especially on FNA, is therapeutically relevant. We describe cytological, histological, and immunohistochemical features of BC and BSQCC. Numerous cytologic features were documented in cytologic preparations. Similar features and architecture were evaluated in the resections. Immunohistochemical results were recorded. Histologically confirmed BC (n = 3) and BSQCC (n = 3) were included. Five FNAs of SCC, (four with histologic follow-up) were studied for comparison of cytological, histological, and immunohistochemical findings. In cytologic preparations of BC/BSQCC, cells were arranged mostly as tightly cohesive clusters (n = 4) or singly and in clusters (n = 2) with a predominance of clusters. Cytologic features of BC and BSQCC were similar: palisading (n = 6), crush artifact (n = 6), hyperchromasia (n = 5), focal nuclear molding (n = 6; very rare in 2/6), nucleoli, usually pinpoint (n = 3), scant cytoplasm (n = 6), necrosis (n = 5), apoptosis (n = 4), squamous differentiation (n = 1). BSQCC tended to have occasional larger cells, including keratinizing cells in one case. Histologic sections (n = 6) showed neuroendocrine features, including organoid arrangements, nests, and palisading. BC and BSQCC show overlapping features with SCC and LCNEC in cytological and histological specimens. Unlike SCCs, BC/BSQCC lack prominent nuclear molding, show tightly cohesive cell clusters, and demonstrate palisading. However, immunostains were the very helpful and probably necessary to accurately diagnosing BC/BSQCC, which show the immunostaining pattern of p63 (+), HMWCK (+), and TTF-1 (-).     

Atypical fibroxanthoma of skin: an electron microscope study.

The ultrastructure of two atypical fibroxanthomas of skin is described. Most of the tumour cells were elongate, and contained abundant rough endoplasmic reticulum, well developed Golgi zones, and numerous small vesicles and filaments, the latter sometimes being related to masses of electron-dense material near the plasma-lemma. Their nuclei often showed deep surface indentations. The appearances were similar to those found in the socalled myfibroblasts that occur in granulation tissue. Multinucleated giant cells and lipid-laden cells in the tumours appeared to be merely modified forms of the basic cells type.     

Canine cutaneous spindle cell tumours with features of peripheral nerve sheath tumours: a histopathological and immunohistochemical study

In veterinary medicine, the term peripheral nerve sheath tumour is usually restricted to neoplasms that are closely associated with an identified nerve. Thirty-three cases of canine cutaneous tumours previously classified as spindle cell tumours with features resembling peripheral nerve sheath tumours were examined. Two histological patterns were identified: dense areas of spindle shaped cells resembling the Antoni A pattern and less cellular areas with more pleomorphic cells resembling the Antoni B pattern. Immunohistochemically, all tumours uniformly expressed vimentin and 15/33 (45.4%) had scattered and patchy expression of S-100. Laminin expression was found in 25/33 (75.7%) tumours and collagen IV labelling occurred in 14/33 (42.4%). Expression of protein gene product 9.5 was detected in 31/33 (93.9%) of tumours and neuron specific enolase labelling was present in 27/33 (81.8%). Glial fibrillary acidic protein was only expressed within the cytoplasm of some large multinucleated cells in one tumour. These findings suggest that any cutaneous tumour with one of the two histopathological patterns described above should be described as a cutaneous peripheral nerve sheath tumour and that expression of S-100, laminin and collagen IV may be used to define a schwannoma.     

Gross, histological and immunohistochemical features of mucormycosis in the platypus

Nine male and five female adult free-living platypuses, obtained in a prospective capture-release study from northern Tasmania, exhibited gross features of cutaneous mycosis caused by Mucor amphibiorum. The lesions were present on the hind limbs (six cases), front limbs (four), tail (five), dorsal trunk (three) and ventral trunk (one). They varied in size, and ranged from raised red nodules or plaques, which sometimes exuded purulent material, to ulcerated lesions with central cavitation, red exuding centres and raised epidermal margins. Older lesions were covered either partly or fully by thickened and irregular epidermis. Histological examination of skin biopsies revealed discrete, poorly encapsulated granulomas, or more commonly a diffuse granulomatous or pyogranulomatous inflammation. Inflammatory cells consisted of neutrophils or eosinophils, sparse plasma cells and lymphocytes, many macrophages and occasional multinucleated giant cells. Fibrovascular tissue was diffusely and irregularly scattered in the granulomatous regions. Sphaerules characteristic of M. amphibiorum infection were observed in all lesions. The cutaneous distribution of the lesions and the natural history of the platypus indicated that entry of M. amphibiorum may have been via superficial skin wounds. T cells were the predominant infiltrating lymphoid cells in the diffuse lesions, indicating the importance of the cell-mediated response to infection.     

Malignant melanoma with neuroendocrine differentiation: clinical, histological, immunohistochemical and ultrastructural features of three cases

AIM: To document the clinical, histological, immunohistochemical and ultrastructural features of three malignant melanomas showing neuroendocrine differentiation. METHODS AND RESULTS: Three patients, two with primary cutaneous melanoma and one with nasal mucosal melanoma, subsequently developing or simultaneously presenting with metastatic malignant melanoma, were studied by conventional histological technique, immunohistochemistry of formalin-fixed paraffin-wax embedded tissues, and electron microscopy of epoxy-resin-embedded tumour tissue. Tumours showed either small cell or conventional malignant melanoma cell morphology. One of the three primary melanocytic lesions (the nasal melanoma) exhibited neuroendocrine differentiation immunohistochemically. All three metastatic malignant melanomas showed, in varying combinations, immunohistochemical and ultrastructural evidence for neuroendocrine differentiation: they were positive for the melanocytic markers, S100 protein, HMB-45, Melan-A and tyrosinase, and the neuroendocrine markers chromogranin, synaptophysin and neurofilament protein. Ultrastructural study in two of the metastases revealed neuroendocrine granules but no lattice-bearing melanosomes. CONCLUSIONS: The cases described are the most comprehensively investigated malignant melanomas showing neuroendocrine differentiation to date, and the first to document neuroendocrine differentiation ultrastructurally in these tumours. Malignant melanoma with neuroendocrine differentiation therefore needs to be recognized among the other, better known variants of malignant melanoma.     

Neuroblastic tumors associated with opsoclonus-myoclonus syndrome: histological,immunohistochemical and molecular features of 15 Italian cases

The aim of this study was to investigate the histological, immunohistochemical and molecular features of a series of children with neuroblastic tumors (NTs) and opsoclonus-myoclonus syndrome (OMS). Of 1187 children (age 0-15 years) with previously untreated NTs registered between 1979 and 1995, 15 (1.3%) had OMS at presentation. The majority of patients showed favorable biological characteristics, such as lack of amplification of the neuroblastoma-associated avian myelocytomatosis homolog MYCN oncogene and aneuploid nuclear DNA content. Tumor histology was reviewed according to the International Neuroblastoma Pathology Classification. Histology of the 15 cases of NTs with OMS was ganglioneuroblastoma, intermixed, in 10 patients; ganglioneuroma, maturing, in 1; and neuroblastoma in 4. Of 15 tumors, 12 (10 ganglioneuroblastomas, 2 neuroblastomas) showed abundant interstitial or perivascular lymphoid infiltrates, the latter often organized in secondary lymphoid follicles. The three remaining cases had only minimal infiltrates. A review of 91 cases of age- and stage-matched neuroblastic tumors not associated with OMS tested as controls showed that the degree of lymphoid infiltration was significantly lower than that detected in OMS-related tumors. Furthermore, lymphoid follicles were always present in the latter tumors, whereas they were detected only in a few ganglioneuroma, intermixed tumors from the control group. In conclusion, ganglioneuroblastoma, intermixed subtype, lack of MYCN amplification, aneuploid DNA content and presence of lymphoid infiltrates may contribute to favorable prognosis in NTs associated with OMS.     

Atypical polypoid adenomyoma of the uterus: A reappraisal of the clinicopathological and immunohistochemical features

Atypical polypoid adenomyoma (APAM) is an uncommon uterine mixed epithelial and mesenchymal tumor. The discrimination from endometrial carcinoma remains to be clarified. In this study, we compared the clinicopathological and immunohistochemical features between 36 APAMs and 48 endometrial carcinomas. APAM with a highly complex structure (n?=?13) coexisted with atypical hyperplasia (n?=?5) and endometrial carcinoma (n?=?1). Two patients had endometrial carcinomas at 1 and 102 months. Four patients recurred at 1–57 months but none died of disease. The fibromuscular stroma demonstrated 3 uncharacterized features: a broad bundle (10/36), a lobular structure separated by the stromal branches (26/36), and the extension of fibromuscular stroma underneath the surface epithelium (31/36). However, these features were not seen in endometrial carcinomas except the vaguely lobular pattern. Both APAM and endometrial carcinoma showed a similar immunostaining pattern except high Ki67 index in endometrial carcinomas (p?<?0.05). Our study suggests that the distinct features of the fibromuscular stroma can aid in the differential diagnosis between APAM and endometrial carcinoma.     

Helicobacter heilmannii gastritis: a histological and immunohistochemical trait

AIM: Biopsies of the gastric antrum were reviewed over a period of 10 years to determine the prevalence of Helicobacter heilmannii in symptomatic subjects from this geographical area and to relate its presence to distinctive histopathological and immunohistochemical features. METHODS: Biopsies from 7926 symptomatic patients were reviewed. Ten serial sections were stained with haematoxylin and eosin for conventional histology. Another 10 sections were stained with the Gram method for spiral bacteria. When H heilmannii was suspected, 10 additional serial sections were stained with methylene blue to obtain homogeneous colouring. An equal number of sections from patients affected by isolated H heilmannii or H pylori gastritis were analysed by immunohistochemistry to evaluate lymphoid aggregate/mucosal lymphocyte clonality (CD20 and CD3) and tumour necrosis factor alpha (TNF-alpha) in stromal cells. RESULTS: The prevalence of H heilmannii was 0.1% (eight of 7926), whereas H pylori was present in 60.7% of patients (4813 of 7926). In two of the eight H heilmannii positive patients both helicobacters were found. In all subjects infected by H heilmannii only, distinctive histology (lymphocyte exudation into gastric foveolae) was seen. Lymphoid aggregates, chronic mucosal inflammation with patchy activity, and the absence of epithelial mucus depletion were regular features of H heilmannii gastritis. Immunohistochemistry did not reveal different lymphocyte clonal patterns between H pylori and H heilmannii gastritis: CD20 positive cells were predominant in the centre of aggregates and mucosal infiltrates, whereas CD3 positive cells were prevalent at the periphery of follicles. Only H pylori gastritis showed a significant increase in TNF-alpha positive stromal cells. CONCLUSION: These data suggest that an unusual lymphocyte reaction, with the tendency to invade the foveolar lumen, is a distinctive histopathological aspect of H heilmannii chronic gastritis, although further studies in a larger series are necessary to confirm this fact. Nevertheless, lymphocyte clones do not differ qualitatively from those found in H pylori infection. Moreover, compared with H heilmannii, H pylori provokes a more intense release of TNF-alpha, suggesting that different inflammatory responses exist to these two organisms.     

Conjunctival biopsy in Sjögren''s syndrome: correlations between histological and immunohistochemical features

A primary tumour of the right atrium with morphological, ultrastructural and immunohistochemical features of a synovial sarcoma is described. This appeared to have arisen from a benign so-called mesothelioma of the atrio-ventricular node and had metastasized to the lungs. The histogenesis and relationship of these two tumours are discussed.