Immunostaining for CD31 and CD34 in Kaposi sarcoma.

AIMS: To evaluate antibodies directed against CD31 (JC70/A) and CD34 (QBEND/10 and anti-HPCA-1) more extensively in Kaposi sarcoma; to assess their value in routine diagnosis; and to compare them with the traditional endothelial cell markers Ulex europaeus agglutinin 1 (UEA-1) and factor VIII related antigen. METHODS: Twenty four cases of Kaposi sarcoma were studied retrospectively. All specimens had been fixed in formalin and embedded in paraffin wax. The antibodies were applied using the Streptavidin biotin technique in all cases except for UEA-1, for which an indirect two stage method was used involving peroxidase conjugated anti-ulex as the secondary antibody. RESULTS: Tumours were classified into those showing angiomatoid or lymphangiomatoid elements and spindle cell lesions. Universal labelling of all lesions and virtually all elements within lesions was seen with the anti-CD34 antibodies QBEND/10 and HPCA-1. Labelling of spindle cells was less consistent with JC70/A but both markers were superior to the traditional endothelial cell markers UEA-1 and factor VIII related antigen. CONCLUSIONS: These data confirm that Kaposi sarcoma is a tumour of endothelial cell origin. They shed further light on the histogenesis of this complex tumour and demonstrate that immunostaining for CD34 and CD31 can be used as an aid to diagnosis in routinely processed tissue.

Solitary and generalized variants of spindle cell xanthogranuloma (progressive nodular histiocytosis).

Twelve cases of solitary spindle cell xanthogranuloma, seven of which had originally been misdiagnosed as dermatofibroma/benign fibrous histiocytoma, were clinicopathologically compared with four cases of progressive nodular histiocytosis, a rare generalized non-X histiocytic disorder. Clinically, a single brown-yellowish papule or nodule is characteristic of solitary spindle cell xanthogranuloma, multiple generalized lesions of progressive nodular histiocytosis. Solitary spindle cell xanthogranuloma occurs with decreasing frequency on the head, neck, upper trunk, or occasionally the extremities of young adults (aged 20-40 years), progressive nodular histiocytosis mostly on the trunk of older patients (aged 40-60 years), both without sex predilection. Histologically, both entities are characterized by predominance (> 90%) of spindle-shaped histiocytes arranged in a storiform pattern. Other mononuclear (vacuolated, xanthomatized, scalloped, oncocytic) and multinucleate (Touton) histiocytes are also regularly seen. Immunohistochemically, both entities exhibit a macrophage/dendritic cell lineage positive for KP1/Ki-M1p (CD68), HAM 56 and factor XIIIa as well as for smooth muscle specific actin and HHF35. Ultrastructurally, dense, regularly laminated, myeloid or pleomorphic cytoplasmic inclusions may be found, but no Birbeck granules are present. This study documents that both solitary spindle cell xanthogranuloma and progressive nodular histiocytosis are distinct entities within the spectrum of a xanthogranulomatous reaction characterized by predominance of spindle-shaped histiocytes.

Immunocytochemistry in the diagnosis of Kaposi's sarcoma and angiosarcoma.

Immunocytochemistry in the assessment of Kaposi's sarcoma and angiosarcoma is reviewed, with emphasis on the technical appraisal of the appropriate panel of markers. Problems incurred in the interpretation of the pathological spectrum of both tumours are discussed.

Reticulohistiocytoma and multicentric reticulohistiocytosis. Histopathologic and immunophenotypic distinct entities.

The clinicopathological and immunohistochemical features of four patients with systemic multicentric reticulohistiocytosis (MR) were compared with five cases of solitary and one case of multiple reticulohistiocytoma (RH), which were confined to the skin only. The MR cases mostly affected the limbs of older women, while RH affected young male adults without preference to site. Characteristically, both entities consisted of oncocytic mononuclear histiocytes (with granular eosinophilic cytoplasm similar to oncocytic thyroid cells) and multinucleated histiocytes with a ground-glass appearance, which appeared to be much larger (> 200 microns) and bizarre in cases of RH compared with cases of MR (50-100 microns). In RH a variable number of vacuolated, spindle-shaped, and xanthomatized mononuclear histiocytes were also present. Immunohistochemical profiles showed positivity of mononuclear histiocytes with HHF35, factor XIIIa, and LN3 (HLA-DR), with a variable number of multinucleated histiocytes in RH showing binding with peanut agglutinin. In mono- and multinucleated histiocytes in both entities macrophage markers KP1 (CD68), KiM1P, HAM56, lysozyme, and alpha 1-antitrypsin were positive. However, macrophage markers MAC387 (L1 antigen) and Leu-M1 (CD15) were negative. Vimentin was universally positive in both conditions, with all other markers (S100, desmin, smooth muscle-specific actin, and QBEnd 10 [CD34]) negative. This study shows that histology supplemented by immunocytochemistry delineates MR from RH and immunohistochemical profiles indicate a cell lineage relationship between RH and adult xanthogranuloma.

Cutaneous crystalline deposits in myeloma.

BACKGROUND: Myeloma is a plasma cell malignancy that usually presents with systemic manifestations or symptoms related to bone involvement. We describe the first case of crystalline protein deposition in the skin as the initial manifestation of myeloma. OBSERVATIONS: Crystals were found mainly in the extracellular space in the dermis of both involved and uninvolved skin in the absence of plasma cell infiltration. Crystals were also found in conjunctival tissue and bone marrow. CONCLUSIONS: We have described a unique case of myeloma that presented as facial and eyelid swelling. There were crystalline deposits in the skin and conjunctivae, but mechanisms of crystal formation and the factors causing local deposition were not established. However, treatment of the underlying disorder leads to resolution of the cutaneous features of crystal deposition.

Verruciform xanthoma: an immunocytochemical study.

Verruciform xanthoma is a rare lesion that occurs predominantly on the oral mucosae, but also on other mucosal sites and on the skin. We report an immunocytochemical analysis of the xanthoma cells in three cases of verruciform xanthoma (two vulval and one scrotal), and also attempt to identify human papilloma virus (HPV) as a possible trigger for the production of these lesions. We employed a panel of seven histiocytic markers (CD68 [KP1], KiM1P, HAM 56, lysozyme, vimentin, peanut agglutinin and factor X111a) and two others to identify HPV involvement (CAMVIR-1 and bovine papilloma virus-1 [BPV-1]). Results showed the xanthoma cells to be positive for CD68, KiM1P, HAM 56 and vimentin, with less consistent labelling for peanut agglutinin and lysozyme. CAMVIR-1 and BPV-1 were negative in all three cases. These findings support the view that the xanthoma cells are derived from a monocyte macrophage lineage and fail to demonstrate HPV as the cause.

Immunocytochemistry in the diagnosis of malignant melanoma.

The role of immunocytochemistry in the routine diagnosis of malignant melanoma is reviewed, with particular emphasis on the potential technical and pathological interpretive problems that may occur. Careful evaluation of the appropriate panel of markers is discussed, along with details of cross-reactivity of markers with tumours of non-melanocytic derivation. Future developments in immunocytochemistry within the field of proliferation indices assessments are highlighted.

Retiform hemangioendothelioma. A distinctive form of low-grade angiosarcoma delineated in a series of 15 cases.

Fifteen cases of a distinctive type of low-grade angiosarcoma of the skin are described. Most tumors presented in the second to fourth decades of life, the youngest patient being 9 years old and the oldest 78 (mean age, 36 years). There was no sex predilection. Six tumors arose on the lower limb, four on the upper limb, three on the trunk, and one each on the penis and the scalp. One case arose in the setting of chronic lymphedema and another following radiotherapy for carcinoma of the uterine cervix. Distinctive morphologic features were the presence of long arborizing blood vessels arranged in a retiform pattern (reminiscent of normal rete testis) lined by monomorphic hobnail endothelial cells, a very prominent lymphocytic infiltrate in most cases, and the focal presence of papillae with hyaline collagenous cores, similar to those seen in malignant endovascular papillary angioendothelioma (Dabska's tumor). With a median follow-up of 7.25 years in 14 cases, retiform hemangioendothelioma has proved to be a low-grade neoplasm that recurs frequently but has a very low metastatic rate. The single regional lymph node metastasis in this series was from a case with a biphasic pattern in which only the spindle cell component was represented in the metastasis. There have been no tumor-related deaths, underlining the importance of accurate distinction from conventional angiosarcoma. This distinction is facilitated principally by the absence of dissection between individual collagen bundles and the absence of endothelial atypia or mitotic activity. The precise relationship between retiform hemangioendothelioma and Dabska's tumor is uncertain, possibly because cases of the latter may not be homogeneous.

Juvenile and adult xanthogranuloma. A histological and immunohistochemical comparison.

Thirteen cases of juvenile xanthogranuloma (JXG) and 13 cases of adult-type xanthogranuloma (AXG) were compared at the light and immunohistochemical levels. Histologically, four main cell types (vacuolated, xanthomatized, spindle-shaped, and "oncocytic") were seen in variable proportions (from monomorphous to mixed variants) with different types of giant cells (nonspecific, foreign body, Touton, and "ground-glass"). Giant cells were more prominent in AXG than in JXG; oncocytic cells (characterized by an eosinophilic, slightly granular cytoplasm similar to thyroid oncocytic cells) and mostly periodic acid-Schiff (PAS) negative giant cells with a ground-glass appearance (6 of 26) were not observed in classic JXG (i.e., occurring in children < 2 years old). Immunohistochemically, JXG and AXG gave similar results: most xanthogranuloma cells labeled strongly with KiM1P and vimentin, while HHF35 and HAM56 stained less intensively. Factor-XIIIa (FXIIIa), KP1 (CD68), and HAM56 stained mostly in the periphery of the lesions. Some markers gave variable results: peanut agglutinin (PA), 60%; alpha-1-antitrypsin, 50%; lysozyme, 25%; LN3 (HLA-DR), < 10% of cells positive. Others were negative: S-100, MAC387 (L1 antigen), LeuM1 (CD15), desmin, smooth muscle-specific actin, and QBEND10 (CD34). This profile helps to delineate xanthogranuloma from histological stimulants such as dermatofibroma (which is FXIIIa+, LN3+, KP1-, and PA-) and multicentric reticulohistiocytosis (which is FXIIIa-, KP1+, PA-, and HHF35-).

Spindle-cell non-pleomorphic atypical fibroxanthoma: analysis of a series and delineation of a distinctive variant.

Atypical fibroxanthoma is a bizarre, cytologically malignant but usually clinically benign, lesion which typically arises in sun-damaged skin of the head and neck region in the elderly. Classically, its morphology is said to represent the dermal counterpart of pleomorphic malignant fibrous histiocytoma. We have identified 10 cases of a more monomorphic spindle-celled, fascicular variant which, paradoxically, was often mistaken for a clinically malignant lesion because it lacked the pleomorphism of conventional atypical fibroxanthoma. These tumours all arose in the head and neck region as polypoid lesions in the elderly. The tumours were confined to the dermis, often had an epidermal collarette, showed an eosinophilic fascicular morphology and were highly mitotic. All 10 were vimentin positive and five showed very focal actin positivity. Desmin, keratin and S-100 protein were negative in all cases. The clinical course was benign in all cases, justifying their accurate recognition. The principal differential diagnoses are spindle cell squamous carcinoma, spindle cell melanoma and leiomyosarcoma. Immunohistochemistry plays a key role in this distinction.

Histologic and immunohistochemical study comparing xanthoma disseminatum and histiocytosis X.

BACKGROUND AND DESIGN: As xanthoma disseminatum and histiocytosis X share clinicopathologic features, difficulties in diagnosis can arise. The use of immunocytochemical markers for S100 protein, factor XIIIa, lysozyme, alpha 1-antitrypsin, for adherence of peanut agglutinin and of antibodies LN3 (HLA-DR), Leu-M1 (CD15), QBEnd/10 (CD34), MAC 387, and KP1 (CD68) as an aid to conventional histology has been studied in routinely fixed skin biopsy specimens from seven patients with xanthoma disseminatum and 12 patients with histiocytosis X. RESULTS: Typically xanthoma disseminatum occurs in discrete foci below an intact epidermis with individual cells set within a delicate fibrillary connective tissue stroma. In contrast, histiocytosis X usually occurs as a diffuse lichenoid infiltrate that can extend to deeper tissues. Epidermal invasion is common and the cells tend to lie free separated by edema fluid. Characteristic histiocytosis X cells are ovoid with an indented or kidney-shaped nucleus that occupies half or more of the cell. Xanthoma disseminatum cells differ in showing irregular scalloped borders, a more extensive cytoplasm, and an ovoid vesicular nucleus. Most xanthoma disseminatum cells labeled strongly for factor XIIIa and with KP1; a few cells labeled only weakly with peanut agglutinin. In contrast, most histiocytosis X cells labeled for S100 protein and with LN3 and peanut agglutinin. All the other markers remained negative in both conditions and were thus noncontributory for differentiating xanthoma disseminatum from histiocytosis X. CONCLUSIONS: We conclude that the differences in labeling patterns are a useful aid to histologic diagnosis of histiocytosis X and xanthoma disseminatum and they also reflect their separate histiogenesis.

Cellular 'neurothekeoma': an epithelioid variant of pilar leiomyoma? Morphological and immunohistochemical analysis of a series.

Cellular neurothekeoma is a recently recognized benign cutaneous neoplasm, which is currently regarded as being of nerve sheath origin and is thought to represent a variant of conventional neurothekeoma (dermal nerve sheath myxoma). Nine new cases presenting predominantly in adolescents or young adults are described. Morphologically they were characterized by short fascicles or small nests of palely eosinophilic epithelioid or spindle-shaped cells which ramified in an ill-defined manner between dermal collagen bundles. Myxoid matrix was absent or sparse. Scattered normal mitoses and multinucleate giant cells were often present. Immunohistochemically all nine cases were strongly NK1/C3 positive, seven were weakly NSE positive and three were smooth muscle actin positive. Staining for S-100 protein, PGP 9.5, epithelial membrane antigen and desmin was negative in all cases. In view of its distinctive architecture and immunophenotype, both of which are totally different from conventional neurothekeoma, it is proposed that cellular 'neurothekeoma' is a separate discrete entity which may represent an epithelioid variant of pilar leiomyoma.

Erythema elevatum diutinum: a clinicopathological study.

Erythema elevatum diutinum is a syndrome of vasculitis in which lesions, typically over the extensor surfaces, showed a mixed inflammatory infiltrate on biopsy. We describe a series of 13 patients. The most common association in our series was with hypergammaglobulinemia; both mono and polyclonal. Chronic infection, not streptococcal, was a less frequent finding although two of three patients had a positive reaction to the intradermal injection of streptococcal antigen. Dapsone remains the initial treatment of choice.

Human orf and milkers' nodule: a clinicopathologic study.

We report the clinical and histopathologic features of 17 patients with orf or milkers' nodule infection. The majority were male, 12 to 65 years of age, and gave a history of contact with farm animals. Most lesions affected the hands or arms, ranged in size from 1 to 3 cm, and occurred on average 3 weeks after presumed exposure. On low-power examination the epidermis showed endophytic strandlike proliferations and the dermal papillae were distended by intense edema. There was massive capillary proliferation and dilation and a dense inflammatory infiltrate. High-power examination revealed epidermal viral cytopathic changes with inclusion bodies, clumping of keratohyalin, and cytoplasmic vacuolation that had a distinctive "spongiform" appearance within follicular structures. We conclude that orf and milkers' nodule infection have distinctive histopathologic features, and, in contrast to some previous reports, viral changes may frequently be found.

The phenotypic heterogenicity of bullous ichthyosis--a case report of three family members.

We present a family with an inherited disorder of cornification. The clinical features are much less severe and developed much later in life than is usual in bullous ichthyosis. Skin biopsy demonstrated epidermolytic hyperkeratosis, a feature typical of bullous ichthyosis. The family is reported both to highlight the wide interfamilial variation that may occur in this condition and the value of histology in classifying this form of ichthyosis.

Pro-inflammatory mediators induce sustained release of prostaglandin E2 from human dermal microvascular endothelial cells.

The vasodilator prostaglandin E2 has been proposed as a mediator of erythema in a variety of cutaneous inflammatory reactions and prostacyclin levels have been found to be elevated in ultraviolet induced erythema. Human recombinant interleukin 1 alpha and lipopolysaccharide induced a concentration- and time-dependent release of prostaglandin E2, but not prostacyclin, from cultured neonatal and adult human dermal microvascular endothelial cells. Prostaglandin E2 was measurable at 2 h after stimulation with 1 U/ml interleukin 1 alpha, levels increased rapidly up to 6 h and more slowly up to 24 h. Lipopolysaccharide (20 micrograms/ml) induced measurable release of prostaglandin E2 between 2 and 4 h after stimulation and release continued up to 24 h when incubation was terminated. With both agonists, release of prostaglandin E2 was inhibited by indomethacin and significantly reduced by cycloheximide. The sensitivity and magnitude of responses of the cutaneous endothelial cells to these pro-inflammatory stimuli appeared to be dependent on their derivation.

Large cell lymphocytoma--a clinicopathological study.

Fourteen patients with large cell lymphocytoma were studied. They presented with solitary or small numbers of grouped nodules on the trunk or head and neck region, which histologically consisted of diffuse and nodular dermal aggregates of lymphoid cells. A proportion of these cells were large with clear cytoplasm and a varying degree of nuclear atypia. An infiltrate of small mature lymphocytes surrounded and extended between the zones of larger cells. Mitotic figures and pleomorphic cells were frequent and, on the basis of this histopathology, an initial diagnosis of cutaneous lymphoma had frequently been made. There were eight male and six female patients with a mean age at presentation of 40 years (range 14-71) who were followed up for a period of between 4 and 31 years (mean = 14.6). Thirteen of the 14 are alive and well, and there has been no evidence of systemic involvement in any of the patients; one patient died of chronic renal failure and pneumonia. Monoclonal antibody studies on paraffin sections showed the presence of lymphoid cells of B and T cell lineage in large cell lymphocytoma. We believe that these patients have a variety of cutaneous lymphocytic infiltrate, large cell lymphocytoma, which has characteristic clinical and histological features and is important to recognize because of its benign course. Large cell lymphocytoma has been used to describe a nodular lymphoid infiltrate of the skin composed principally of large follicular centre cells. Often these lesions had been diagnosed as reticulum cell sarcoma but, on follow-up, all the patients were alive and well.(ABSTRACT TRUNCATED AT 250 WORDS)

Histopathologic features of superficial granulomatous pyoderma.

Study of the histopathologic pattern of 28 cases of superficial granulomatous pyoderma demonstrated an ulcerative, verrucous pyoderma of the superficial dermis. Focal abscesses in the subepidermis or dermis were juxtaposed with granuloma formation and plasma cell inflammation. Hemorrhage and granulation tissue were present. The clinical lesions are indolent, and this feature is confirmed by chronic inflammatory elements, including sinus tract formation and focal fibrosis. Superficial granulomatous pyoderma must be added to the histologic differential diagnosis of the vegetative and ulcerative granulomas: blastomycosis, tuberculosis verrucosa cutis, and bromoderma.