Epithelioid cell histiocytoma--histogenetic and kinetics analysis of dermal microvascular unit dendritic cell subpopulations

BACKGROUND: Epithelioid cell histiocytoma (ECH), also known as epithelioid fibrous histiocytoma, is a peculiar dermal tumor, which can mimic melanocytic, vascular, epithelial, or other histiocytic lesions. Thought to arise from dermal dendrocytes, most ECH contain approximately 50% FXIIIa+ histiocytic dendrocytes, but not all lesional cells express FXIIIa. A putative fibroblastic component has not been characterized. METHODS: We analyzed the differentiation and cell kinetics of dermal microvascular unit cells in 12 previously reported ECH using antibodies to FXIIIa, CD68 (KP1), CD34, CD117, CD31, smooth muscle actin, collagen type 1 aminopropeptide, and MIB-1, using single and double immunostains. RESULTS: In ECH, many variably sized CD34/CD31+ tumor vessels with actin+ myopericytes were surrounded by epithelioid-to-dendritic cells of three types. About 5-80% were dendritic histiocytes that expressed FXIIIa but not CD31 or KP1. Fibroblasts, in some cases showing mild nuclear pleomorphism, were usually collagen type 1+, but CD34 and actin- in 11/12 cases. One 'early' ECH had 40% CD34+ epithelioid cells, admixed with 50% FXIIIa+ histiocytes. Most ECH had about 2-20% KP1+, CD117+ mast cells. Mast cell numbers increased with FXIIIa+ histiocyte numbers and the intensity of FXIIIa expression. MIB-1/FXIIIa double-labeling showed only rare cycling histiocytes, with numerous cycling fibroblasts and endothelial cells. CONCLUSIONS: Our findings support the impression that ECH is a vascular fibrous histiocytoma. The constituent cells appear to arise from the activation of resident microvascular CD34+ dermal fibroblasts and the accumulation of FXIIIa+ dendritic stromal assembly histiocytes. The CD34+ cells appear to differentiate toward collagenous fibrocytes in association with histiocytes and mast cells in forming collagenous stroma and vessels. ECH is a tumor composed of all requisite cell types consistent with the origin from the dermal microvascular unit.     

Epithelioid Cell Histiocytoma with Granular Cells

Epithelioid cell histiocytoma (ECH) is regarded as a variant of fibrous histiocytoma. It is not readily recognized as fibrous histiocytoma because of its unconventional histologic features and its resemblance to Spitz nevus. The ECH reported herein was from a 50‐year‐old man who presented with an asymptomatic, 1.5 cm, polypoid mass of unknown duration on his posterior shoulder. Histologic examination revealed epidermal collarette and dermal sheets of epithelioid cells with granular cytoplasm. Both fine and coarse granules were noted in the cytoplasm. They were PAS positive and diastase resistant. Many dilated vessels were also noted in the lesion. A panel of immunostains including S100, vimentin, CD68, and factor 13A was done. The lesional cells were reactive with vimentin, CD68, and factor 13A, and non‐reactive with S100. These results favored exclusion of Spitz nevus and granular cell tumor, and supported the histologic impression of ECH. Both fine and coarse cytoplasmic granules were reactive with CD68. The latter finding supports that the cytoplasmic granules in this ECH represent lysosomes as in granular cell tumors.     

Unusual presentation of multiple epithelioid cell histiocytomas

Epithelioid cell histiocytoma (ECH) is a variant of dermatofibroma that presents typically as a solitary nodule. We report a case of a 20-year-old male who presented with a bleeding nodular lesion on the left arm followed a month later by a nodule on the right nostril. Both lesions had epithelioid cells in the dermis, with focal Factor 13a and CD68 immunoreactivity. The left arm lesion, in addition, showed staghorn vasculature as well. Both lesions were interpreted as ECH. The patient had an unremarkable medical history. To the best of our knowledge, multiple ECHs have not been reported in the literature. An appropriate diagnosis of ECH is important as the differential diagnosis usually includes melanocytic lesions.     

Aneurysmal Benign Fibrous Histiocytoma with Atrophic Features

Aneurysmal benign fibrous histiocytoma is an uncommon pathologic variant of dermatofibroma. In addition to the features of a typical dermatofibroma, it has large cleft-like or cavernous blood-filled spaces with numerous hemosiderin pigments. It should be differentiated from angiomatoid malignant fibrous histiocytoma, malignant melanoma, and vascular tumors such as Kaposi''s sarcoma and angiosarcoma. Atrophic dermatofibroma is also a rare variant of dermatofibroma, and the combination of aneurysmal and atrophic features is rarer still. We report a case of aneurysmal benign fibrous histiocytoma with atrophic features in a 27-year-old male who had a grayish-brown atrophic patchy lesion on his back for 2 years.     

Cutaneous “fibroma-like” perivascular epithelioid cell tumor: A case report and review of literature

Perivascular epithelioid cell tumors (PEComas) are a group of lesions sharing the common features of co-expression of melanocytic and myogenic markers, with focal association of the cells with vascular walls. The PEComa group exhibits a wide range of morphologies. A “fibroma-like” variant of PEComa has been recently described. The case reported herein is that of an infant with tuberous sclerosis complex (TSC) presenting with a lip mass. Excisional biopsy showed a moderately cellular tumor composed of spindled to stellate cells embedded within a collagenized stroma. The cells showed focal perivascular accumulation and positivity for both melanocytic (HMB-45) and myogenic (desmin) markers. This is the fifth reported case of “fibroma-like” PEComa in literature and the youngest patient to date. All of the “fibroma-like” PEComas were found in patients with tuberous sclerosis—hence, the diagnosis of this entity should prompt a workup for TSC; conversely, a fibroma-like lesion in a patient with TSC or with TSC-related conditions should be evaluated using melanocytic and myogenic markers. Melanocytic and myogenic markers are also useful in differentiating “fibroma-like” PEComa from other differential diagnoses such as fibroma and benign fibrous histiocytoma.     

Cutaneous epithelioid hemangioendothelioma

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor of endothelial cell origin. We describe an EHE arising on the plantar surface of the foot that was treated as verruca vulgaris for several years before a biopsy showed EHE. We discuss the clinical and histopathologic differential diagnoses for these tumors and review additional cases in which EHE has been mistaken for benign entities clinically.     

EMA positivity in epithelioid fibrous histiocytoma: a potential diagnostic pitfall

Background: Epithelioid fibrous histiocytoma (EFH) represents a morphologic variant of cutaneous fibrous histiocytoma (FH) but can lack many characteristic features. The presence of epithelioid cytomorphology may mimic other dermal neoplasms. Our anecdotal experience of epithelial membrane antigen (EMA) expression in some examples of EFH has caused diagnostic difficulty. Our aim was to examine the immunohistochemical profile and incidence of EMA expression in EFH. Methods: Forty‐four cases of EFH were retrieved from consultation files. Clinicopathologic and immunohistochemical features were evaluated. Results: Membranous EMA positivity was found in tumor cells in 27/42 cases (64%). Focal positivity for factor XIIIa was found in 10/14 (71%) and D2‐40 in 14/27 (52%). Scattered smooth muscle actin (SMA)‐positive tumor cells were seen in 11/43 (25%). Focal positivity for claudin‐1 was found in 3/42 (7%). CD163 staining highlighted stromal macrophages; however, in five cases it was difficult to exclude focal staining of tumor cells. Tumor cells were consistently negative for pan‐keratin, AE1/AE3, S100, CD31, CD34, CD68, desmin, p63, GFAP and CD45/LCA. Conclusion: Frequent EMA expression in EFH represents an unexpected finding and constitutes a potential diagnostic pitfall. Although of uncertain significance, this finding, when combined with established morphologic differences, raises the possibility that EFH is unrelated to classic FH. Doyle LA, Fletcher CDM. EMA positivity in epithelioid fibrous histiocytoma: a potential diagnostic pitfall.     

Benign fibrous histiocytoma with osteoclast-like giant cells in an infant

Abstract:  Benign fibrous histiocytoma is a common soft tissue tumor that usually occurs in adults and is relatively rare in childhood. This report describes a 7-month-old Caucasian boy with an enlarging firm congenital nodule on his occipital scalp. Histologic analysis revealed a benign fibrous histiocytoma with osteoclast-like giant cells. Benign fibrous histiocytoma with osteoclast-like giant cells is a rare histologic variant.     

Epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia) arising on the extremities

Background: Epithelioid hemangioma (EH) is a benign vascular proliferation usually accompanied by a mixed inflammatory infiltrate. Methods: Skin biopsy specimens from four patients with EH on the extremities were studied. Architecture, extent of vascular proliferation and the presence of epithelioid endothelial cells were evaluated. The features of the inflammatory infiltrate were also assessed, including the distribution, depth, predominant cell type, presence of germinal centers, and distribution and number of CD30+ cells. Results: All cases showed the typical lobular pattern of small vessels centered about a ‘feeder’ vessel. Larger vessels were lined by epithelioid endothelial cells. The mixed inflammatory infiltrate was nodular, perivascular and periadnexal. Germinal centers were seen in two cases. Large activated CD30+ lymphocytes were seen in all cases. Conclusions: EH can lead to diagnostic confusion with cutaneous lymphoma and other entities, especially when its mixed inflammatory infiltrate predominates over its vascular component and contains large activated CD30+ lymphocytes. Awareness that the presence of CD30+ activated lymphocytes is not specific for lymphoma and recognition of the vascular component is critical for proper diagnosis of EH. Cham E, Smoller BR, Lorber DA, Victor TA, Cibull TL. Epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia) arising on the extremities.     

Palisading cutaneous fibrous histiocytoma

We report 6 cases of an unusual variant of cutaneous fibrous histiocytoma in which nuclear palisading is a prominent feature. The lesions were equally distributed between males and females with a widely variable age range. Half of the cases occurred on the digits. Histopathologically, the lesions were characterized by areas of nuclear palisading with formation of Verocay-like bodies in addition to the more typical features of the "fibrous" variant of cutaneous fibrous histiocytoma. The differential diagnostic features between these lesions and those of other tumors in which nuclear palisading is seen are discussed.     

Epithelioid cell histiocytoma with underlying artery damage

Although epithelioid cell histiocytoma is considered a variant of fibrous histiocytoma (dermatofibroma), the histogenesis of this condition remains controversial. A recent investigation suggested the possibility that epithelioid cell histiocytoma is an angioformative fibrous histiocytoma. We report a case of epithelioid cell histiocytoma underlying a damaged artery. This epithelioid cell histiocytoma with a central area of hemorrhage was associated with a medium-sized artery in the reticular dermis running vertically up to the lesion. Both the artery in the reticular dermis and its centrally branched artery in the subcutaneous tissue showed mural injury and intraluminal epithelioid endothelial proliferation. Immunohistochemically, the labeling rate for each of the antibodies studied in the epithlioid cells was as follows: 40% for Factor XIIIa, 5% for CD34, 20% for factor VIII-related antigen, and 10% for alpha-smooth muscle cell actin. This case may support the view that epithelioid cell histiocytoma is a vascular and angioformative fibrous histiocytoma.     

Benign fibrous histiocytoma (dermatofibroma) of the face: clinicopathologic and immunohistochemical study of 34 cases associated with an aggressive clinical course.

Thirty-four cases of fibrous histiocytoma (dermatofibroma) arising on the face are reported. These neoplasms occurred frequently in females (24 female, 10 male) and showed a broad age range (12 to 85 years; mean: 43.6 years, median: 41 years). The neoplasms originated on the forehead (nine cases), the cheek (eight cases), the eyebrow (four cases), the temporal region (three cases), the nose (two cases), and the ear (one case); in seven cases the location face was given only. Five of 27 cases with follow-up information (median: 5 years) recurred locally; in one case four recurrences were excised within 8 years. The majority of cases extended into the subcutis and deep soft tissue including striated muscle (50% of cases). Histologically, only the minority of cases was composed entirely of histiocytoid and spindle-shaped tumor cells arranged in a storiform growth pattern. In many cases cellular fascicles and bundles of spindle-shaped tumor cells were noted in addition to classical morphological features of fibrous histiocytoma. A moderate mitotic rate (mean: 2.97 mitoses in 10 HPFs) was observed, and in few cases increased atypia was evident. Frank tumor necrosis and/or vascular invasion were not identified. Immunohistochemical studies revealed Factor XIIIa positivity in 13 out of 17, focal CD68 positivity in 6 out of 10, and alpha-smooth muscle actin positivity in 16 out of 19 cases tested. These lesions should be distinguished from dermatofibrosarcoma protuberans, including its fibrosarcomatous variant, leiomyosarcoma, and low-grade myofibroblastic sarcoma. Cases of fibrous histiocytoma of the face have to be excised with wider margins in comparison with examples of classical fibrous histiocytoma occurring on the extremities because of diffuse infiltration, involvement of deeper structures, and an increased rate of local recurrences.     

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.     

Pedunculated hemangiopericytoma-like tumor: peculiar fibroepithelial polyp or fibrous histiocytoma variant

Abstract:  Pathologists are continually challenged with the difficult task of discriminating between innocuous disease processes and potentially malignant entities. Apropos of this concern, we present a series of three cutaneous polypoid lesions that simulated fibroepithelial polyp, yet upon close scrutiny yielded histologic features of solitary fibrous tumor (SFT) or hemangiopericytoma. These pedunculated lesions showed a storiform pattern of spindled cells with interspersed gaping vascular channels reminiscent of SFT or hemangiopericytoma. Interestingly, the immunohistochemical staining profile of these lesions was negative for CD34 and positive for bcl-2 and factor XIIIa. These findings were discordant with SFT and suggest a relationship with fibrous histiocytoma. We propose that this entity represents a hitherto described variant of fibrous histiocytoma known as pedunculated hemangiopericytoma-like fibrous histiocytoma.     

Myxofibrosarcoma in the skin

Myxofibrosarcoma, also known as myxoid malignant fibrous histiocytoma, is increasingly recognized as a distinct malignant neoplasm of fibroblastic origin with variable clinical and histopathologic features. Myxofibrosarcomas are among the most common malignant mesenchymal neoplasms of older adults, and approximately two thirds develop within the dermis or subcutis. Herein, we describe the clinicopathologic features of four cases of myxofibrosarcoma involving the skin. Three of these cases were initially misdiagnosed as benign cutaneous neoplasms, two as myxoid neurofibroma. These cases illustrate the clinicopathologic spectrum encompassed by myxofibrosarcoma in the skin and highlight the diagnostic difficulties it may present.     

Desmin and CD34 positivity in cellular fibrous histiocytoma: an immunohistochemical analysis of 100 cases

Background: Cellular benign fibrous histiocytoma (CBFH) represents a morphologic variant of cutaneous fibrous histiocytoma (FH). Because of its relative monomorphism and frequent fascicularity, CBFH can easily be mistaken for a malignancy. In fact, CD34, often used to distinguish CBFH from dermatofibrosarcoma protuberans (DFSP), can also be positive. To add to the confusion, desmin positivity may also be observed in a subset of CBFH. Desmin and CD34 expression often cause interpretative difficulty which may lead to misdiagnosis. Our aim was to examine the incidence of desmin and CD34 expression in CBFH. Methods: One hundred consecutive cases of morphologically typical CBFH were retrieved from consultation files. Clinicopathologic and immunohistochemical features were evaluated. Results: SMA positivity was found in tumor cells in 93 of 100 cases (93%). Desmin positivity was found in 32 of 100 cases (32%). CD34 was positive in 6 of 100 cases (6%). There was no evident correlation between immunophenotype and anatomic site or other clinical variables. Conclusion: Frequent desmin (32%) and occasional CD34 (6%) expression are encountered in CBFH. Desmin positivity can be explained on the basis of myofibroblastic differentiation. The occasional CD34 positivity in a subset of CBFH should not be a deterrent from making the correct pathologic diagnosis, based on characteristic morphologic features.     

Atypical cutaneous fibrous histiocytoma

We report seven cases of atypical cutaneous fibrous histiocytoma, which appears to be a variant of cutaneous fibrous histiocytoma (dermatofibroma). These patients are all middle-aged women (mean, 39 years old) with small nodules occurring on the trunk and limbs. The lesions are characterized by marked focal cellular atypia, the absence of mitoses, and xanthomatous changes in both mononuclear and giant cells--all found within a small dermal nodule (approximately 1 cm) separated from an acanthotic epidermis by a Grenz zone. Their benign nature is demonstrated by the absence of recurrence, even after 9 years follow-up time.     

Clear cell fibrous papule with NKI/C3 expression: clinical and histologic features in six cases

Fibrous papule of the nose is a common benign lesion of dermal fibroblast lineage. Two unusual variants have been described, namely, fibrous papule with granular cells and fibrous papule with clear fibrocytes. We report a second case series (six cases) of clear cell fibrous papule to add to the first series of 9 cases. Clinical and histologic features in our cases are similar to those in the first series. All of our specimens were dome-shaped, 2- to 5-mm skin-colored to slightly erythematous papules on the faces of three male and three female adults ranging from 18 to 48 years of age. All but one lesion were on the nose. Clinical differential diagnoses included fibrous papule, verruca, basal cell carcinoma, and a variety of other neoplasms. Histologically, dermal aggregates of clear cells with finely granular to vacuolated cytoplasm, and centrally located nuclei, were found. Most specimens also contained ectatic capillaries, and all showed evidence of irritation or trauma. Periodic acid-Schiff stain was negative in all specimens to which it was applied (5/6). Neural, melanocytic, and epithelial origins were eliminated by negative staining with S-100, Mart-1, cytokeratins, epithelial membrane antigen, and carcinoembryonic antigen, performed on some of the specimens. A mesenchymal nature was confirmed in one specimen staining strongly positive for vimentin. Five of six cases stained positively for CD68, and all five cases studied were strongly and diffusely positive for NKI/C3. Factor XIIIa stain highlighted scattered dendritic cells within the lesion but was otherwise negative in all six cases studied. Recognition of this variant of fibrous papule is important to distinguish this benign lesion from other clear cell neoplasms.     

结缔组织增生性色素痣四例临床病理分析

目的 探讨结缔组织增生性色素痣的病理学特点及鉴别诊断.方法 对4例皮肤结缔组织增生性色素痣的临床表现、组织学表现、免疫组化及荧光原位杂交(FISH)特点进行分析.结果 4例结缔组织增生性色素痣中,男2例,女2例,年龄19 ～ 30岁,平均26.5岁;皮损位于四肢3例,外阴1例.组织学特点:均为皮内痣,病变左右对称,痣细胞呈上皮样和(或)梭形,聚集成团或单个散在分布于增生的纤维组织之间,均未见淋巴细胞聚集、坏死或溃疡.免疫组化显示,3例痣细胞为S100和Melan A阳性,2例为P16阳性;Ki-67阳性指数均小于5％;2例间质细胞为凝血因子FⅫ和CD34阴性.荧光原位杂交(FISH)显示结缔组织增生性色素痣在6p25(RREB1)、6q23 (MYB)、6p11.1-q11.1(Cep6)及11q13(CCND1)4个基因位点均无拷贝数异常.结论 结缔组织增生性色素痣是一种组织学独特的良性黑素细胞痣,ki-67 、S100、Melan A、凝血因子FⅩⅢ等免疫组化染色和黑素瘤FISH检测有助于其与皮肤纤维组织细胞瘤和黑素瘤鉴别.