Inflammatory myofibroblastic tumor of the skin.

We report a case of inflammatory myofibroblastic tumor (IMF) of the skin in a female with a history of Wegeners granulomatosis. The patient had a painless, erythematous, and indurated lesion of the left elbow. The resected specimen revealed a 4 cm x 3 cm nodule involving the entire dermis and superficial portions of subcutis with a stellate profile at scanning magnification. There were spindle cells in fascicles and whorls and a mixed inflammatory cell infiltrate of plasma cells, lymphocytes, neutrophils, and eosinophils. The spindle cells were immunoreactive for vimentin, muscle specific actin, and smooth muscle actin. The polyclonal and polymorphous nature of the inflammatory cells was confirmed by immunohistochemical studies. This is the first case of IMF of the skin documented by immunostaining.     

Cutaneous inflammatory pseudotumor – a spectrum of various diseases?

BACKGROUND: Inflammatory pseudotumor (IPT) also known as inflammatory myofibroblastic tumor (IMT) or plasma cell granuloma (PCG) has been rarely reported in the skin. METHODS: We describe five patients with cutaneous IPT and present clinicopathologic features along with detailed immunohistochemical analysis including anaplastic lymphoma kinase (ALK)-1. RESULTS: The patients age ranged from 15 to 89 years with a median of 56 years. All patients presented with solitary, firm, papules and nodules. There was no evidence of constitutional symptoms, local recurrence, or lymph node involvement. Histopathological examination revealed two distinct patterns; one type (n = 3) displayed dense, lymphoplasmacytoid infiltrates containing lymphoplasmacytoid cells and plasma cells with occasional germinal centers and hyalinized collagen bundles but was devoid of a myofibroblastic component. It showed features of tumors previously described as cutaneous PCG. Although an infectious etiology, including Borrelia burgdorferi-specific DNA, could not be demonstrated, we observed many features that overlapped with those of fibrous nodules of acrodermatitis chronica atrophicans. The other pattern (n = 2) revealed spindled myofibroblasts focally arranged in a fascicular pattern, an admixed lymphoplasmacytoid infiltrate set in a background of thickened collagen bundles, findings akin to the conventional type of IMT. The cases with a myofibroblastic component (n = 2) did not show any evidence of ALK-1 reactivity. CONCLUSIONS: We believe that the term cutaneous IPT subsumes lesions of diverse etiology. Tumors with detectable myofibroblasts represent true cases of IMT. Cutaneous PCG is a discrete disorder biologically distinct from conventional IMT representing a reaction pattern that is also found in disorders, such as spirochete-induced fibroid nodules and localized chronic fibrosing vasculitis.     

Inflammatory myofibroblastic tumor of the tongue: report of an unusual case in a teenage patient

Inflammatory myofibroblastic tumor is a rare and distinctive lesion composed of myofibroblastic cells accompanied by an inflammatory infiltration of plasma cells, lymphocytes, and eosinophils that mainly affects viscera and soft tissues of children and young adults. It clinically manifests as a mass with rapid development that may occur at almost any site of the body, but predominantly in the lungs or the upper respiratory tract. It rarely arises in the oral cavity with approximately 15 cases reported in that location. We describe a case of an inflammatory myofibroblastic tumor of the tongue, confirmed by both histopathologic and immunohistochemical analysis, occurring in a 14-year-old boy that spontaneously regressed after the surgical procedures for its diagnosis. Because of some aggressive clinical, histological, and radiological features, this lesion may be confused with a malignant tumor. Therefore, its correct recognition is important to avoid unnecessary extensive and radical therapeutic approaches.     

Immunoglobulin-producing cells in the inflammatory infiltrates of cutaneous tumors. Immunocytologic identification in situ.

An immunocytochemical technique has been developed for the identification in situ of immunoglobulin-producing cells in tissues fixed in Bouin's solution and embedded in paraffin. Technical details are discussed as well as the application of the technique to the study of plasma cells in the inflammatory infiltrate around cutaneous tumors. Preliminary results have been obtained with basal cell epitheliomas, squamous cell carcinomas, and malignant melanomas. IgA-producing cells were present in all tumors. IgG-producing cells were present in variable frequency, depending on the type of tumor, and IgM-producing cells were found only in basal cell epitheliomas and squamous cell carcinomas.     

Immunofluorescent and immunoperoxidase staining of antibodies to fibrous keratin. Improved sensitivity for detecting epidermal cancer cells

Microscopically controlled surgery (Mohs' surgery) is a widely accepted technique because it provides total extirpation of skin tumors with maximum conservation of tissue. However, in poorly differentiated tumors it is often difficult microscopically to recognize individual tumor cells in the midst of an inflammatory cell infiltrate, in fibrotic tissue, in connective tissue around blood vessels, in nerve sheaths, and in fascial planes. We have developed techniques to differentiate tumor cells, derived from the epidermis, from the normal nonkeratinizing tissue of mesodermal origin or the inflammatory cell infiltrate. In frozen sections, indirect immunofluorescence techniques with polyclonal antibodies to fibrous keratin allowed rapid identification of tumor cells of basal and squamous cell carcinoma. Immunoperoxidase staining proved to be a remarkably sensitive method for the identification of such carcinoma cells in both frozen and paraffin-embedded sections. When used in combination with the precise mapping techniques of Mohs' surgery, these reliable and specific stains permitted greater accuracy in assessing the total resection of an invasive tumor.     

The histopathologic spectrum of regression in atypical fibroxanthoma

Background: Atypical fibroxanthoma (AFX) with prominent fibrosis, sclerosis and hyalinization, and near‐total tumor regression is rare. Methods: Eight cases of AFX presenting with fibrosis were reviewed as to their tumor architecture, the degree and pattern of fibrosis and the associated inflammatory cell infiltrate. Results: Seven of eight cases had an exophytic architecture, with ulceration in one case. The degree of fibrosis ranged from 10% to 90%. Early fibrosis (2/8 cases) occurred as thickened sclerotic collagen bundles, either dispersed between the neoplastic cells or as septa imparting a multilobular appearance. Advanced fibrosis (6/8 cases) was associated with lamellar sclerosis, keloidal features, hyalinization and with near‐total tumor replacement. Prominent fibrosis rimming the periphery was present in all tumors. An associated lymphoid cell infiltrate with plasma cells and occasionally eosinophils was observed. Conclusions: Fibrosis with prominent sclerosis and hyalinization replacing the tumor is rare in AFX. Advanced fibrosis, in the absence of a history of prior trauma or surgery, may indicate spontaneous regression. These cases emphasize the importance of recognizing this subset of AFX in order to avoid misinterpretation, particularly in cases with few residual atypical cells. Stefanato CM, Robson A and Calonje JE. The histopathologic spectrum of regression in atypical fibroxanthoma.     

Monophasic sarcomatoid carcinoma of the scalp: a case mimicking inflammatory myofibroblastic tumor and a review of cutaneous spindle cell tumors with myofibroblastic differentiation

BACKGROUND: The evaluation of malignant cutaneous spindle cell tumors is challenged by a diagnostic differential that comprises neoplasms of diverse histogenesis, and a broad immunohistochemical panel may confound the diagnosis when the results suggest multiple lines of differentiation, such as with a combined myofibroblastic and epithelial phenotype. METHODS: We report the case of a solitary scalp nodule that quickly became locally metastatic. A comprehensive panel of immunohistochemistry markers and electron microscopy was evaluated to determine the differentiation of the spindle cells. RESULTS: The tumor, consisting of wavy and slender spindle cells with predominantly bland nuclei, showed immunoreactivity to vimentin, smooth muscle actin, and muscle-specific actin. AE1/AE3, CK5/6, and MNF-116 antibodies were weakly positive in rare cells. However, 34betaE12 showed diffuse positivity in the spindle cell population, thus supporting the diagnosis of a sarcomatoid carcinoma with myofibroblastic differentiation. CONCLUSIONS: The use of 34betaE12 is essential for the evaluation of myofibroblastic spindle cell tumors with rare cytokeratin reactivity. However, even with immunohistochemical and electron microscopic studies, the diagnosis of spindle cell tumors can be confounded by the multiplicity of nosologic equivalents, such as carcinosarcoma, spindle cell carcinoma, and metaplastic carcinoma. The nomenclature of these spindle cell tumors is discussed.     

Lichen planus of the nail matrix with predominant plasma cell infiltrate

Lichen planus (LP) is an inflammatory dermatitis of idiopathic origin that can involve the skin, mucous membranes, hair and nails. Histologically, LP is characterized by compact orthokeratosis, wedge-shaped hypergranulosis, irregular acanthosis, damage to the basal cell layer and a band-like inflammatory infiltrate in the upper dermis. Lymphocytes are the predominant cells making up the infiltrate, along with a few macrophages, eosinophils and plasma cells. In addition, melanophages are often found in the upper dermis adjacent to the damaged basal cells.(1) We describe a patient with a lesion of the toenail clinically and histopathologically consistent with LP, but with a band-like inflammatory infiltrate composed primarily of plasma cells. Previously, only three other cases of LP with plasma cell predominant infiltrate have been reported, none of which involved the nail matrix.     

Morphoea with prominent plasma cell endoneuritis

Morphoea (localized scleroderma) is a cutaneous inflammatory condition characterized by the development of indurated and discoloured plaques. The histological features of morphoea typically include a superficial and deep perivascular and periadnexal chronic inflammatory infiltrate associated with variable degrees of dermal and/or subcutaneous sclerosis. The infiltrate is typically composed of lymphocytes, macrophages and conspicuous plasma cells. The early stages of morphoea may have a very prominent inflammatory infiltrate associated with subtle sclerosis. In addition, the inflammatory infiltrate may show a perineural and rarely intraneural distribution. We report two cases of morphoea that histologically showed plasma cell endoneuritis associated with subtle dermal sclerosis. These two cases highlight the potential for diagnostic confusion with infectious and inflammatory diseases, particularly leprosy and lupus.     

A Case of Angiolymphoid Hyperplasia with Eosinophilia of the Lower Eyelid

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a subcutaneous angioproliferating tumor with a characteristic inflammatory infiltrate that consists mainly of lymphocytes and eosinophils. A 24-year-old man presented with a firm single asymptomatic erythematous papule on the lower eyelid. Histopathological findings showed a proliferation of blood vessels lined with epithelioid cells and perivascular infiltration of lymphocytes and eosinophils. We report a case of ALHE occurring on an unusual site.     

Myoid differentiation in dermatofibrosarcoma protuberans and its fibrosarcomatous variant: clinicopathologic analysis of 5 cases

We report a series of five cases of dermatofibrosarcoma protuberans, four of which were fibrosarcomatous and all of which showed histologic and immunohistochemical evidence of focal myoid/myofibroblastic differentiation (accounting for up to 5% of each tumor). These lesions were identified amongst 208 cases of dermatofibrosarcoma protuberans including 24 examples of the fibrosarcomatous variant. Three of the five patients were male and two were females; all were adults (37–72 years). One case arose on the scalp and two cases each on the abdominal wall and upper trunk. All tumors were less than 5cm in diameter and preoperative duration ranged from 2 months to 10 years. In three cases with follow-up there was no recurrence. Histologically, all tumors were typical fibrosarcomatous or ordinary dermatofibrosarcoma protuberans but for the presence of scattered to confluent nodules and bundles of eosinophilic spindle cells associated with well-defined cytoplasmic margins and vesicular nuclei associated with focal stromal hyalinization. While the typical dermatofibrosarcoma protuberans areas were CD34 positive, the myoid areas were negative for this antibody and positive for smooth muscle actin and pan-muscle actin. All tumors were desmin negative. Recognition of myofibroblastic differentiation in fibrosarcomatous dermatofibrosarcoma protuberans is important not only because it gives support to the theory of a fibroblastic/myofibroblastic line of differentiation for this type of tumor, but also because it might be a source of confusion with other myofibroblastic lesions (e.g. myofibromatosis, adult myofibroma), especially when small biopsies are evaluated.     

Plasma cell infiltrate in common acquired melanocytic nevus

The presence of plasma cells in melanocytic lesions has been considered in literature as a sign of concern, when evaluated in the appropriate context. Plasma cells have been evaluated in halo nevus, but they are not frequently reported in non-halo common acquired nevus. Our claim was to study how common and frequent plasma cells are in the latter type of nevi. Therefore, we examined 280 of these nevi and selected the cases with an inflammatory infiltrate, even if mild. We then looked for plasma cells in the inflammatory infiltrate in the hematoxylin-eosin routine sections and selected 17 cases in which plasma cells (even if only occasional) could be found in the hematoxylin-eosin staining. Out of these 17, plasma cells were easily found in four cases, which were then further studied with immunohistochemistry for epithelial membrane antigen. The percentage of plasma cells varied in these four cases from 0.5% to 7%. No relation between the amount of plasma cells and either the location of the nevus or the location of the inflammatory infiltrate could be established. We conclude that the main point of this study is not to trust the presence of plasma cells as a solid criterion on its own, when evaluating a melanocytic lesion.     

Immunohistochemical characterization of plasma cells in Zoon's balanoposthitis and (pre)malignant skin lesions

A retrospective study in 9 patients with Zoon's balanoposthitis was done to determine the immunoglobulin class distribution in the plasma cellular infiltrate. This was carried out on paraffin-embedded specimens using an unlabelled antibody peroxidase-antiperoxidase method. In all lesions IgG-producing plasma cells predominated. IgA- and IgD-positive cells were also present in about equal quantities but fewer than IgG. IgM-positive cells were either absent or present in very low numbers. Especially in erosive lesions a high number of plasma cells was noticed. The kappa/lambda ratio was variable with a preference for lambda in 5 of 8 cases. These findings are suggestive of a nonspecific polyclonal stimulation of B cells, which might be caused by a persistent infection. The above-mentioned findings were compared with premalignant and malignant skin lesions in which a major amount of plasma cells was present in the inflammatory infiltrate. Comparable results were obtained with slight variations. The role of plasma cells in these infiltrates is discussed.     

Syringocystadenocarcinoma Papilliferum: A Case Report and Review of the Literature

Syringocystadenocarcinoma papilliferum (SCACP) is a rare malignant adnexal neoplasm, which is considered as a malignant counterpart of syringocystadenoma papilliferum (SCAP). Clinically, SCACP appears as a nodule, inflammatory plaque, or tumor. The lesion is usually covered with crusts, which are formed by secretion of the apocrine epithelial cells. Histologically, SCACP resembles SCAP, with cystic papillomatous invaginations connected to the skin surface by funnel-shaped structures lined by infundibular epithelium. The stroma of the tumor consists of a dense inflammatory infiltrate of plasma cells and lymphocytes. SCACP differs from SCAP in terms of the architectural and cytological features of the tumor cells, and is characterized by higher nuclear cytoplasmic ratio, nuclear irregularity, coarse chromatin, and increased mitotic activity. However, the immunohistochemical findings of SCACP vary. Since only 49 cases of SCACP have been reported in the English literature, the clinical and histologic characteristics of SCACP have not been fully established. Further studies on the diagnostic criteria for SCACP are warranted. Here, we report a rare case of SCACP and present a review of other relevant literature.     

Myofibroblastic differentiation in atypical fibroxanthomas occurring on sun-exposed skin and in a burn scar: an ultrastructural and immunohistochemical study

Herein, we report the investigation of two cases of atypical fibroxanthoma (AFX). One AFX developed within actinically damaged skin, as is typical, while the other developed within a burn scar within non-sun-exposed skin. The two tumors showed almost identical histopathological, immunohistochemical and ultrastructural features. The tumors were composed of pleomorphic spindled, epithelioid, multinucleated and bizarre cells with enlarged atypical nuclei. Most tumor cells expressed vimentin and about 50% expressed CD10. Some tumor cells also expressed α-smooth muscle actin and CD68. However, there was no expression of cytokeratins, p63, S-100 protein, melan-A, HMB 45, desmin, epithelial membrane antigen or CD34. Ultrastructurally, the tumor cells contained myofilaments with dense patches but lacked plasmalemmal caveolae and basal lamina. The most prominent finding was the identification of fibronexus junctions. In addition, there were tumor cells containing numerous lysosomal granules. In conclusion, we clearly showed myofibroblastic differentiation in AFX by electron microscopy. We report also a case of AFX directly developing within a burn scar in the absence of actinic damage.     

Large neglected ulcerated melanoma mimicking extramedullary plasmacytoma

Amelanotic melanoma, a renowned impersonator, has taken on a new persona. A 63-year-old woman was seen in the emergency room with a chief complaint of back pain after a fall and was discovered to have a 15-cm fungating mottled gray mass independent of bone on the right elbow. Initial workup discovered lytic calvarial lesions, anemia (Hb 7; Hct 20%), and circulating plasma cells consistent with plasma cell myeloma. Biopsy of the elbow mass displayed sheets of plasmacytoid cells, some reactive for CD138. Flow cytometry revealed a substantial portion of the plasma cells in the tumor that were kappa restricted consistent with cutaneous plasmacytoma. The elbow mass was initially signed out as extramedullary involvement by her myeloma. Reevaluation of the mass after the patient experienced an explosive growth of multinodular jet black malignant melanoma on ipsilateral breast revealed MART-1 and S-100 reactivity of the majority of the cells. In retrospect, the elbow mass was a neglected primary amelanotic malignant melanoma with neoplastic plasma cells participating in its chronic inflammatory infiltrate.     

Malignant fibrous histiocytoma of the skin with marked inflammatory infiltrate: a sarcoma mimicking malignant lymphoma

Three cases of malignant fibrous histiocytoma of the skin with a marked inflammatory infiltrate in the stroma are reported. The inflammatory infiltrate, composed mainly of T-lymphocytes, obscured the nature of the neoplasms, and immunohistochemical studies were required to establish the diagnosis. Two tumors arose in the sun-damaged skin of the face, and one tumor arose in the chest wall. One patient developed a local recurrence with histopathologic findings similar to those observed in the original lesion, including the inflammatory infiltrate. Possible differential diagnoses include large cell lymphoma, inflammatory pseudotumor, inflammatory leiomyosarcoma, and spindle cell squamous cell carcinoma. The presumed rarity of inflammatory changes in malignant fibrous histiocytoma of the skin is supported by the absence of reported cases.     

HLA-DR antigen expression in primary melanomas of the skin

Ninety-three primary malignant melanomas of the skin were typed immunohistologically for the expression of HLA-DR on tumor cells. HLA-DR-positive stroma cells were HLA-DR-negative or only locally positive in most cases. In 36 (39%) of the lesions more than 10% of the tumor cells were stained by two monoclonal antibodies against the nonpolymorphic portion of HLA-DR. HLA-DR-positive tumor cells were often accumulated at the advancing front of the melanoma. The occurrence of HLA-DR-positive tumor cells was related to tumor thickness and level of invasion. Substantial numbers of HLA-DR-positive tumor cells were found in half of the tumors thicker than 1.5 mm and in only 18% of flatter lesions. The highest percentage of HLA-DR-positive tumors was found in the group of melanomas invading the reticular dermis (level IV). The majority of tumors (18/24) that had metastasized within an observation period of 0-32 months were HLA-DR-positive. Regarding the mononuclear cell infiltrate, no correlation between the degree of overall infiltrate and the expression of HLA-DR by the tumor cells was found. The infiltrate within the tumor, however, was more often marked in HLA-DR-positive than in HLA-DR-negative melanomas.     

Demonstration of S 100 protein in malignant melanoma of the skin. Pattern of distribution and significance for determination of tumor thickness

Paraffin sections of 110 histologically proven malignant melanomas were incubated with a polyclonal antibody against S-100-protein. The avidin-biotin-peroxidase technique was used. A positive reaction was found in 109 cases. The staining pattern was inhomogeneous, suggesting heterogeneity within the tumor. The tumor thickness was measured in HE sections and corresponding sections that had been incubated with an antibody against S-100 protein. The results were as follows: 48.5% of the melanomas incubated with anti-S-100 protein showed a greater tumor thickness than the HE sections. The deviation between the two criteria was 15%. Four cases with the histological diagnosis of "melanoma in situ" showed S-100-positive cells within the subepidermal inflammatory infiltrate. Incubating sections of malignant melanoma with anti-S-100-protein facilitates the recognition of neoplastic cells within the inflammatory infiltrate.     

An ulcerated lesion due to HSV-2 infection with a CD56+ cell predominant inflammatory infiltrate

CD56+ rich inflammatory infiltrates have been described in several cutaneous inflammatory conditions. However, CD56+ cells rarely account for more than 10% of the cells in such infiltrates. In certain conditions, such as insect bites or infection with herpes virus, CD56+ cells can be up to 43% of the cells in the infiltrate. This contrasts with what is observed in natural killer (NK)-cell lymphomas, which show a diffuse, atypical infiltrate in which most of the cells are CD56+. In this report, we describe a lymphocytic infiltrate in an ulcerated lesion on the lip of a 53-year-old man resulting from infection with herpes simplex virus type 2. CD56+ cells represented 80 to 90% of the infiltrate, showing atypical morphologic features, and clusters of CD56 positive cells were also observed.