Lymphomatoid papulosis: ultrastructural, immunohistochemical and gene analytical studies

Ultrastructural, immunohistochemical and gene analytical studies were carried out on a 39-year-old patient with lymphomatoid papulosis. Two different cell groups were demonstrated in the papulonodular eruptions: large atypical cells with multiple nuclei that were well stained with anti-Tac, but not with Leu 3a, and other cells that possessed prominent hyperchromatic nuclei and which stained well with Leu I and Leu 3a but not with anti-Tac. Gene analytical studies using EcoRI, BamHI and HindIII revealed no rearrangement, indicating a non-clonal T-cell proliferation unlike malignant T-cell lymphoma. These results suggest that the present case was benign.     

Apocrine nevus: light microscopic, immunohistochemical and ultrastructural studies of a case

The apocrine nevus (AN) is a rare tumor occurring in the upper chest and the axilla. We report a case of a AN in a 33-year-old female occurring unilaterally. The presenting complaint related to tenderness and swelling in the right axilla. The initial impression was hidradenitis suppurativa. The gross specimen revealed the presence of irregular thickening just beneath the dermal subcutaneous interface. Microscopically the lesion was composed of mature apocrine glands with apical snouts. The glands were arranged in lobules divided by thin fibrous septa. immunohistochemical studies revealed the following profile in the glandular epithelium: positive low molecular weight cytokeratin, epithelial membrane antigen, and gross cystic disease fluid protein reactivity and negative high molecular cytokeratin and S-100 protein reactivity. Carcinoembryonic antigen reactivity was found in the duet epithelium. Ultrastructural studies revealed cells lining the lumen of the glands with a concentration of granules in the apical region and light and dark granules. These findings support the previously described light microscopic observations and provide unreported ultrastructural studies in this rare tumor.     

Erythrokeratodermia variabilis: immunohistochemical and ultrastructural studies of the epidermis

Immunohistochemical and ultrastructural study of the epidermis was performed in a 53-year-old female with erythrokeratodermia variabilis (EKV) before and after treatment with the aromatic retinoid Etretinate (RO 10-9359). Aberrant expression of cytokeratin PKK2 (Labsystems, Helsinki, Finland) in lesional EKV stratum corneum was observed; this feature disappeared after Etretinate therapy. A normal distribution of DR-positive dendritic Langerhans' cells was seen in diseased, control and post-treatment skin specimens. The striking finding of this study was thus the shift to a basal cell-type keratin reactivity in stratum corneum in lesional skin, perhaps a reflection of cytoskeleton features related to cell adhesion. Increased adhesion between the cells in stratum corneum might account for the retention type of hyperkeratosis characteristic of EKV.     

Pigmented hidrocystoma of the eccrine secretory coil in the vulva: clinicopathologic, immunohistochemical and ultrastructural studies

A case of pigmented hidrocystoma of eccrine secretory coil is presented. A 47-year-old woman had developed a bluish black small nodule in the anterior portion of the labium minor a few years before entry. Microscopically, the cyst was lined by eosinophilic columnar epithelium with abundant brownish granules. There was a vague suggestion of decapitation secretion focally in the epithelial layer of cuboidal cells. This layer expressed distinct reactivity against CA19-9 with no reactivity for human milk fat globule-1 (HMFG-1). These features demonstrated that the cyst was not of apocrine nature but of eccrine derivation. In addition, positive immunoreaction for cytokeratin (CK)7, CK8 and CK19 defined the cyst as originating from the secretory coil of the sweat gland. Ultrastructurally, melanosomes in various stages were identified in most of the epithelial cells. These findings suggest that the present case was a hidrocystoma of eccrine secretory coil with abnormal melanin accumulation.     

Light microscopic, immunohistochemical, and ultrastructural alterations in patients with melasma

Despite new technologies, few studies have assessed the histologic alterations in patients with melasma. Using current technologies, the present study was designed to re-evaluate the light microscopic, immunohistochemical, and ultrastructural changes of the hyperpigmented and adjacent normal skin of patients with melasma. Twenty-one patients were included in this study. Two millimeter punch biopsies were taken from the hyperpigmented and adjacent normal skin of the face. The integrity of the epidermis and dermis was assessed by light microscopy, computer-assisted image analysis, immunohistochemistry, and electron microscopy. Stains included hematoxylin-eosin and Fontana-Masson for melanin detection. Immunostaining was performed using Mel-5 antibody and CD1a antibody as markers for melanin and Langerhans cells, respectively. However, mild lymphohistiocytic infiltrates were present in 75% of the hyperpigmented areas. The areas of hyperpigmentation showed increased deposition of melanin in the epidermis and dermis of all cases. There was a statistically significant increase in the content of epidermal melanin. There were no quantitative increases in melanocytes in the hyperpigmented areas of skin. However, the melanocytes in the hyperpigmented areas were larger, intensely stained cells with very prominent dendrites. Electron microscopy revealed more melanosomes in keratinocytes, melanocytes, and dendrites in the involved skin in comparison to the uninvolved skin. The results of this study suggest that melasma is a consequence of specific hyperfunctional melanocytes that cause excessive melanin deposition in the epidermis and dermis.     

Osteosarcomatous changes in malignant melanoma. Immunohistochemical and ultrastructural studies of a case

Immunohistochemical and ultrastructural studies were conducted to elucidate the nature and origin of osteosarcomatous changes in malignant melanoma in a 43-year-old Japanese man. Immunohistochemical studies with the use of antisera against human S-100 protein and neuron-specific enolase demonstrated positive reactions in the tumor cells within the osteosarcomatous area. Ultrastructurally, the neoplastic cells showed marked similarities to those from osteosarcomas. Additionally, occasional neoplastic cells contained round or ellipsoidal osmiophilic organelles, presumably melanosomes. These findings indicate that osteosarcomatous changes in malignant melanoma are produced by the dedifferentiated melanoma cells.     

Cutaneous epithelioid malignant nerve sheath tumor with rhabdoid features: a histologic, immunohistochemical, and ultrastructural study of three cases

INTRODUCTION: Malignant rhabdoid tumors are morphologically defined as sheets of loosely cohesive cells with eccentric nuclei and hyaline, paranuclear inclusions. Although originally described as a distinctive renal neoplasm of childhood, these tumors have since been described in all age groups and in a variety of extrarenal sites. In the latter setting, it is thought that the rhabdoid phenotype is comprised of histogenetically unrelated tumors, that regardless of histogenesis, pursue a biologically aggressive behavior. METHODS: We report on the clinical, histologic, immunophenotypic, and ultrastructural characteristics of three cases of cutaneous malignant rhabdoid tumor. RESULTS: Each of the cases arose on the trunk or the extremity of elderly men. None of the patients had neurofibromatosis. All of the lesions histologically showed sheets of loosely cohesive polygonal cells with eccentric nuclei and hyaline paranuclear inclusions. Each of the cases showed the following immunophenotype: S-100 (+), synaptophysin(+), vimentin (+), alpha smooth muscle actin (-), CD-30 (-), HMB-45 (-), and pankeratin(-). Ultrastructure of two of the cases yielded similar results showing paranuclear filamentous aggregates of intermediate filaments, cell membrane dense plaques, and rudimentary cell junctions consistent with nerve sheath differentiation. Tonofilaments, dense bodies, microtubules, neurosecretory granules, and melanosomes were not identified. Each of the patients died of widely metastatic disease within 1 year of diagnosis. CONCLUSIONS: Cutaneous epithelioid malignant nerve sheath tumor is a potentially aggressive tumor capable of showing rhabdoid differentiation thus simulating a variety of neoplasms. Immunophenotyping and ultrastructural analysis reliably discriminates these lesions from melanoma, de-differentiated carcinoma, lymphoma, and rhabdomyosarcoma.     

Myxoid dermatofibrosarcoma protuberans: morphological, ultrastructural and immunohistochemical features

Two uncommon cases of dermatofibrosarcoma protuberans with prominent myxoid changes are presented. The tumors appeared as large multinodular cutaneous plaques that arose at the sites of excision of previous tumors some years earlier. In addition to limited Fibrous storiform features, focally observed in deep and peripheral portions of the tumors, a diffuse myxoid pattern could be observed. The latter consisted of homogeneous areas of rare, stellate or spindle-shaped cells, haphazardly scattered in abundant myxoid matrix. Cells of myxoid neoplastic tissue showed mainly a positive immunoreaction for fibrohistocytic markers and the absence either of muscular, neural of human progenitor cell antigens. Mitotic figures were fewer and cell proliferation rates were lower in myxoid as compared to those of typical dermatofibrosarcoma protuberans used as a control. The ultrastructural examination of myxoid areas revealed a prevalent Fibroblast-like cell population showing dilated cytoplasmic vesicles, sometimes containing glycosaminoglycans-like substances. The extent of myxoid changes together with the characteristic morphological, ultrastructural and immunohistochemical features confirm that myxoid dermatofibrosarcoma protuberans is a distinct variant of this fibrohistiocytic tumor to be considered in the differential diagnosis among myxoid tumors of the skin.     

Squamous cell carcinoma, malignant melanoma and malignant fibrous histiocytoma arising in burn scars

Summary The most common cancer arising from an old burn scar is squamous cell carcinoma, while malignant melanoma is rare. There are only four reports in the literature on the combination of the more common tumour with a malignant melanoma and only two cases of malignant fibrous histiocytoma alone. This paper reports the first occurrence of the combination of all three types of cancer in burn scars of the same patient. The factors that promote malignant transformation, such as immunological factors and karyotype, are discussed. We also performed an immunohistochemical study using anti-p53 antibodies.     

Genital melanotic macules: clinical, histologic, immunohistochemical, and ultrastructural features

BACKGROUND: Genital melanotic macules are poorly recognized lesions, which appear as isolated discrete macules. Their occurrence, usually as new pigmented lesions in adult life, can cause concern because they can mimic early melanoma. OBJECTIVE: Our purpose was to define the clinical, histologic, immunohistochemical, and electronmicroscopic features of genital melanotic macules. METHODS: History and clinical features of 10 patients (5 female, 5 male) were assessed in detail. Histologic findings were reviewed in 5 cases, and immunohistochemistry, with the use of the HMB-45 antibody, in 4 cases and electron microscopy in 3 cases. RESULTS: Clinically the lesions varied in color, tan to dark brown/black, and size (0.5-2 cm). Histologic findings showed increased basal pigmentation without atypical features. HMB45 antibody staining was negative. Electron microscopy showed normal morphology and number of melanocytes but increased melanosomes and dermal melanophages. CONCLUSION: Genital melanotic macules are benign, asymptomatic, discrete areas of hyperpigmentation that occur equally in men and women. Histologic, immunohistochemical, and electronmicroscopic study confirms their benign nature.     

Hyaline cells in chondroid syringomas. A light-microscopic, immunohistochemical, and ultrastructural study

The origin and significance of hyaline cells (HC) in chondroid syringomas (CS) is unclear. In a review of 20 CS, we found HC in eight cases. These were studied immunohistochemically, using antibodies to cytokeratin, vimentin, carcinoembryonic antigen, epithelial membrane antigen, desmin, muscle-specific actin, S-100 protein, myoglobin, alpha-1-antitrypsin, chromogranin, glial fibrillary acidic protein, and neuron-specific enolase. HC gave a positive reaction to cytokeratin, vimentin, S-100 protein, and neuron-specific enolase, but not to the other antibodies. Thioflavin-T stain for amyloid was negative. Ultrastructurally, HC contained intermediate filaments in hap-hazard arrangement without specific structures or densities, and had sparse intracytoplasmic organelles and rare desmosomal attachments. Intermediate forms between epithelial cells and HCs were also identified. Our results suggest that HCs are relatively common in Cs (40%) and are more frequent in CS with solid nests and myxoid stroma (relative frequency 62.5%). Immunohistochemically, HCs of CS have a specific phenotype profile; however, ultrastructurally, HCs of CS are not distinct and are similar to HCs in other organs. These results do not suggest an exclusive myoepithelial origin of HCs; it appears that HCs could derive from any epithelial cell type of sweat glands, probably via a regressive process.     

Multinucleate cell angiohistiocytoma: a clinicopathological, immunohistochemical and ultrastructural study

The term 'multinucleate cell angiohistiocytoma' was first introduced by Smith and Wilson Jones in 1985. We report the clinicopathological, immunohistological and ultrastructural findings observed in two patients. Multinucleate cell angiohistiocytoma occurs mainly in middle-aged women and is usually located at acral sites, particularly the distal extremities. Grouped, brown-red, slightly elevated, asymptomatic papules slowly develop over several months until further growth ceases. There is no evidence of systemic disease. Histologically, the dermis shows numerous well developed capillaries with prominent endothelia, large bizarre basophilic and often multinucleate cells with a sparse lymphohistiocytic infiltrate. The immunohistological and ultrastructural findings suggest a fibroblastic differentiation of the large multinucleate cells.     

Lichen striatus. Histological, immunohistochemical, and ultrastructural study of 37 cases

BACKGROUND: Lichen striatus (LS) is a papulosquamous disorder with a distinctive linear distribution. The linearity has been shown to correspond in many cases to the pattern of Blaschko's lines. The etiology is unknown. LS can usually be identified by clinical history and histology of typical lesions. However, the histologic features are diverse and some have stated they are nonspecific. METHODS: In an effort to identify those characteristic features, we have reviewed the routine slides in 37 cases for their diagnostic criteria. Ten cases were studied further by immunohistochemistry. RESULTS: The patient's ages ranged from 1.3 to 49 years with mean age of 17.5 years. A female-to-male ratio was 1.6 to 1. The lesions were predominantly distributed on the extremities in 26/34 cases. The consistent histologic features were: hyperkeratosis (29/37), parakeratosis (21/37) with a few necrotic keratinocytes (28/37) in the epidermis, mild spongiosis (29/37) with exocytosis of lymphocytes (33/37). The dermal infiltrate comprised mainly lymphocytes and macrophages. At the dermal-epidermal junction, the infiltrate was either focal (20/37) or lichenoid (17/37) patterns. Superficial and deep perivascular lymphocytic inflammatory infiltrate was present in most of the cases (33/37). Appendageal involvement (34/37) was in hair follicles (24/37) or eccrine glands or ducts (22/37) or both (12/37). Satellite cell necrosis may be seen (11/37). Colloid bodies were present in 16/37 of the cases. Immunohistochemistry showed that most of the small lymphocytes in the upper dermis and epidermis were positive for CD7. Most of the lymphocytes in the epidermis were positive for CD8. CD1a Langerhans' cells were either decreased (5/10) or increased (3/10) or normal (2/10) in the epidermis. CONCLUSION: The histologic diagnosis of LS can be made on the basis of the combination of these histologic features in the appropriate clinical context. Multiple biopsies may be necessary to determine whether all of these features are present in a given case.     

Cutaneous myxoid fibroblastoma. A histological, immunohistochemical, and ultrastructural study.

A fibroblastic skin tumor with a myxoid matrix is reported that cannot be easily classified as one of the well-known entities of fibrous/fibrohistiocytic and myxoid skin tumors. A 27-year-old white woman presented with a reddish, dome-shaped cutaneous nodule 8 mm in diameter on the left popliteal fossa that had developed spontaneously within the preceding 2 years. There was no sign of recurrence 30 months after excision. Light microscopic examination showed a well-circumscribed tumor confined to the upper dermis and consisting of stellate and spindle-shaped cells arranged loosely in a fascicular pattern resembling tissue cultures of fibroblasts. There were almost no collagen bundles between tumor cells, and Mowry's staining showed large amounts of glycosaminoglycans. Immunohistochemical studies of the tumor cells showed reactivity only to vimentin, whereas markers of histiocytes, dermal dendrocytes, and neurogenic and myogenic differentiation were negative. By electron microscopy, the majority of tumor cells contained elliptical nuclei, but some tumor cells had conspicuous multisegmented nuclei with several large and small nuclear segments connected by thin nuclear bridges (labyrinth nuclei). Single fibrils were found within the interstitium; collagen fibers were rare. Histological and ultrastructural examinations identified tumor cells as fibroblasts. High cellularity distinguishes this tumor from cutaneous myxoma. We conclude that this lesion represents a newly recognized tumor of fibroblastic origin. The name cutaneous myxoid fibroblastoma is proposed.     

Immunological, cytochemical and ultrastructural studies in lymphomatoid papulosis

In lymphomatoid papulosis two histological types can be distinguished, i.e. type A and type B. In the present study various immunological, enzyme-histochemical and ultrastructural techniques were used to investigate the cellular infiltrate in both types of lymphomatoid papulosis. The type A lesions showed a predominance of large atypical cells, relatively few T cells and few or no Langerhans or related cells, as defined by a positive staining for OKT6 and NA I/34 antisera. The immunological, cytochemical and ultrastructural characteristics of these large atypical cells resembled those of the Langerhans cell/interdigitating reticulum cell series. The morphology and marker profile of these large cells resembled those of Reed-Sternberg cells, which suggests a relationship between lymphomatoid papulosis type A and Hodgkin's disease. The type B lesions showed a predominance of small, medium-sized and large cerebriform mononuclear cells with the phenotype of activated T helper cells, and numerous Langerhans and/or related cells. Their cellular composition was similar to that observed in the early stages of mycosis fungoides.     

An immunohistochemical and ultrastructural study of syringocystadenoma papilliferum

BACKGROUND: Syringocystadenoma papilliferum is a benign hamartomatous tumour of the skin. The histogenesis of this tumour is still controversial. There have been few reports regarding immunohistochemical investigations using only a limited range of antibodies and ultrastructural studies on this rare tumour. OBJECTIVES: To elucidate the immunohistochemical and ultrastructural properties of this tumour. METHODS: We investigated the immunohistological patterns of 12 different anticytokeratin (CK) antibodies and several other markers in five cases of this tumour, comparing them with the patterns in adult sweat glands. One of these cases was also evaluated ultrastructurally. RESULTS: The luminal columnar cells of the tumour were mostly positive for CK7 and more than 70% were positive for CK19. These cells showed the heterogeneous expression of CK1/5/10/14, CK14 and CK5/8. These patterns were also observed in the luminal cells in the secretory or the ductal portion of the adult sweat glands. The basal cuboidal cells of the tumour almost constantly expressed CK1/5/10/14, CK5/8, CK14 and CK7 (except for one case), similar to the patterns of basal cells in the transitional portion and myoepithelial cells in the sweat glands. However, the basal tumour cells expressed CK19 and vimentin heterogeneously, and alpha-smooth muscle actin focally (three cases). Ultrastructurally, the constituent epithelial cells were mainly divided into three types: luminal cells, basal cells and clear cells. The luminal tumour cells bore features of the secretory or ductal luminal cells of sweat glands, although they were somewhat immature in appearance. The basal tumour cells were fundamentally basaloid in nature. The clear cells were undifferentiated or primitive in appearance, suggesting stem or progenitor cell properties. Transitional forms between the clear cells and the other two cell types were also identified. CONCLUSIONS: The tumour epithelium was composed of several cell types demonstrating various developmental stages from the primitive clear cells to the basal cells demonstrating a tendency to differentiate toward basal cells in the apocrine transitional portion or myoepithelial lineage, or luminal cells toward the ductal or secretory epithelium. These results support the classical concept that syringocystadenoma papilliferum is a hamartomatous tumour that arises from pluripotent cells.     

Microcystic adnexal carcinoma: a light microscopic, immunohistochemical and ultrastructural study

We report a case of microcystic adnexal carcinoma (MAC) occurring on the upper lip of an 82-year-old woman. Microscopically the tumor showed both pilar and sweat gland differentiation, involved the entire dermis and subcutaneous tissue, and invaded perineural spaces. Immunoperoxidase studies revealed carcinoembryonic antigen to be present in the ductal lining cells and in the amorphous content in the lumen, confirming sweat gland differentiation. The S-100 protein was positive in dendritic cells within the solid cell nests, but negative in cells lining cystic spaces. Ultrastructural study confirmed that the neoplasm was composed of two components, with pilar and eccrine differentiation. The former showed concentric layers of squamous epithelial cells with well-developed desmosomes and cytofilaments. The latter had ductal and alveolar structures; the ultrastructural features included: i) numerous villous folds of plasma membrane to interdigitate each other by focal desmosomes, ii) aggregates of cytofilaments, and iii) basally located myoepithelial cells which were separated from the surrounding stroma by rather thick basement membrane. In addition, distinct amyloid deposition was also observed on ultrastructural examination. To our knowledge, amyloid deposition has not been previously reported in MAC.     

Hidroacanthoma simplex: An ultrastructural and immunohistochemical study

A representative case of hidroacanthoma simplex was studied with routine light microscopy, immunohistochemistry, and electron microscopy. Staining with the periodic acid-Schffi reagent and immunostaining with anti-keratin antibodies were useful in demarcating the tumor cells from adjacent normal epithelium. However, antibodies to carcinoembryonic antigen and epithelial membrane antigen did not help us to segregate or identify the neoplastic cells. Electron microscopy revealed tumor cells markedly different in appearance from luminal cells of the acrosyringium. Hidroacanthoma simplex does not appear to be derived from luminal cells of the acrosyringium. We propose criteria for the histologic diagnosis of this benign neoplasm.