Amelanotic melanoma in a New Zealand White Rabbit (Oryctolagus cuniculus).

A 3.5-year-old intact male double-transgenic New Zealand white rabbit (Oryctolagus cuniculus), apoA-I and LCAT (apolipoprotein and lecithin:cholesterol acyltransferase), was presented with a discrete, raised facial mass (0.5 x 1.0 x 1.0 cm). The mass was surgically excised, with reoccurrence to the same site 88 days later. A second surgical excision was performed, and the rabbit died 3 weeks later from respiratory distress. At necropsy, multiple varying-sized masses were observed in the ventral mandibular region and throughout the lungs, pleura, and diaphragm. On histopathology, the masses were composed of moderately anisocytotic and anisokaryotic polygonal to spindloid cells with moderate finely granular, lightly eosinophilic cytoplasm, having round to oval nuclei with one to several nucleoli and finely stippled chromatin. Mitotic figures were frequent. Lymphatic and venous invasion were noted with neoplastic cells metastasized to the submandibular lymph nodes, lungs, liver, and adventitial surface of the aorta. Fontana-Masson stain was negative for melanin, thereby necessitating immunohistochemistry and transmission electron microscopy. Positive staining with MART-1 (a melanocyte protein marker) combined with transmission electron microscopy revealing type II melanosomes confirmed the diagnosis of an amelanotic melanoma.

The pathology of devil facial tumor disease (DFTD) in Tasmanian Devils (Sarcophilus harrisii).

A disfiguring and debilitating neoplastic condition known as devil facial tumor disease (DFTD) has been discovered in wild Tasmanian Devils (Sarcophilus harrisii) across 51% of its natural range, with population declines of up to 80% in some areas (C. Hawkins, personal communication). Between 2001 and 2004, 91 cases were examined. The tumors presented as large, solid, soft tissue masses usually with flattened, centrally ulcerated, and exudative surfaces. They were typically multicentric, appearing first in the oral, face, or neck regions. Histologically, the tumors were composed of circumscribed to infiltrative nodular aggregates of round to spindle-shaped cells, often within a pseudocapsule and divided into lobules by delicate fibrous septae. They were locally aggressive and metastasized in 65% of cases. There was minimal cytologic differentiation among the tumor cell population under light and electron microscopic examination. The results indicate DFTD to be an undifferentiated soft tissue neoplasm.

Predictive variables for the biological behaviour of basal cell carcinoma of the face: relevance of morphometry of the nuclei.

We did a morphometric analysis of 130 histological sections of basal cell carcinoma (BCC) of the face to find out whether morphometric variables in the structure of the nuclei of BCC cells could serve as predictors of the biological behaviour. We considered the following variables: maximum and minimum diameters, perimeter, nuclear area and five form factors that characterise and quantify the shape of a structure (axis ratio, shape factor, nuclear contour index, nuclear roundness and circumference ratio). We did a statistical analysis of primary and recurring tumours and four histology-based groups (multifocal superficial BCCs, nodular BCCs, sclerosing BCCs and miscellaneous forms) using a two-sided t test for independent samples. Multifocal superficial BCCs showed significantly smaller values for the directly measured variables (maximum and minimum diameters, perimeter and nuclear area). Morphometry could not distinguish between primary and recurring tumours.

Spindle cell rhabdomyosarcoma (so-called) in adults: report of two cases with emphasis on differential diagnosis.

Spindle cell rhabdomyosarcoma (RMS) is a recently described variant of embryonal RMS that carries a relatively favorable prognosis when compared with other forms of RMS. To date, spindle cell RMS has been described only in children. The authors have identified two unusual cases occurring in adults using the following criteria: tumors composed mainly of fascicular, relatively monomorphic spindle-shaped cells that show unequivocal immunohistochemical and ultrastructural evidence of myogenic differentiation. The tumors were identified in a 38-year-old woman and a 56-year-old man, arising in the cheek and left hemidiaphragm, respectively. Both were treated with surgical resection and chemotherapy. The first patient died of uncontrolled local recurrence of her tumor at 27 months after diagnosis, and the second died of metastatic disease at 13 months follow-up. The tumors were composed mainly of fascicles of spindle cells with palely eosinophilic cytoplasm admixed diffusely with sparse polygonal, rounded, or strap-shaped rhabdomyoblasts with brightly eosinophilic cytoplasm and with cross-striations in the first case only. Immunostaining for muscle-related antigens showed staining for smooth-muscle actin (focal), pan-actin HHF-35, desmin, fast myosin, myoglobin, and MyoD1. Both cases were negative for S-100 protein. On electron microscopy, both cases showed neoplastic rhabdomyoblasts with clear-cut sarcomeric differentiation in many of the tumor cells. Spindle cell RMS poses special problems in differential diagnosis when arising in adults and should be distinguished from leiomyosarcoma, malignant peripheral nerve sheath tumor with heterologous rhabdomyoblastic differentiation (malignant Triton tumor), and fibrosarcoma. In view of the good prognosis afforded children with spindle cell RMS and in light of the chemoresponsive behavior of RMS in general, we feel that it is important to identify tumors that meet the criteria for spindle cell RMS occurring in the adult population. However, based on these two cases, it is possible that spindle cell RMS occurring in adults may not be associated with such a favorable outcome.

Clear-cell atypical fibroxanthoma: an uncommon histopathologic variant of atypical fibroxanthoma.

Atypical fibroxanthoma is a superficial variant of pleomorphic malignant fibrous histiocytoma. Histopathologically, it is characterized by a dermal nodule composed of bizarre cells arranged in a haphazard-to-fascicular pattern. These cells are spindle or rounded, pleomorphic and with numerous atypical mitotic figures. Some cells appear polygonal with ample and foamy cytoplasm. We recently encountered two elderly patients with atypical fibroxanthoma on their face. Histopathologically, one of the lesions was composed, almost entirely, of clear cells, whereas in the other one aggregations of clear cells constituted a half of the neoplasm. Atypical multinucleated cells with a Touton-like appearance were present. In addition to clear cells, areas of more conventional atypical spindle cells arranged in fascicles were seen, supporting the diagnosis of atypical fibroxanthoma. PAS staining failed to demonstrate glycogen in neoplastic cells. Immunohistochemistry revealed that neoplastic cells expressed positivity for vimentin, muscle-specific actin, and alpha smooth muscle actin, whereas cytokeratin, S-100 protein, EMA, CEA, and desmin were negative. Ultrastructural studies showed that neoplastic cells contained abundant rough endoplasmic reticulum, mitochondria, and numerous lipid vacuoles within the cytoplasm. Clear-cell atypical fibroxanthoma is a rare variant of atypical fibroxanthoma that should be differentiated from other clear-cell neoplasms of the skin.

A histological morphometric study of nuclear size in benign and malignant neoplasms of the human cheek.

This report describes the application of simple morphometric methods to generate quantitative data on nuclear size from tissue sections of normal, benign and malignant oral epithelium of the cheek. Measurements of nuclear areas of basal and spinous cells from cheek mucosa were made on haematoxylin and eosin-stained sections using a Zeiss VIDAS image analyser. The lesions examined comprised benign squamous cell papillomas and islands of cells from invasive squamous cell carcinomas. Normal control epithelium was obtained from the biopsy margins of non-neoplastic lesions. The nuclear areas (AN) were obtained by direct measurement whereas the nuclear diameters (DN) were determined automatically. In both basal and spinous strata, values for both these nuclear parameters were lowest in normal tissue and increased progressively through benign papillomas, with the highest values being found invariably in carcinomas. Statistically significant differences were detected between both normal and carcinoma and between papilloma and carcinoma. The morphometric parameters AN and DN are of value in distinguishing benign from malignant lesions of the human cheek.

Leiomyosarcoma versus myofibrosarcoma: observations and terminology.

Two spindle cell sarcomas, which showed similarities in light microscopic histology and immunostaining and were diagnosed as leiomyosarcomas by these criteria, were compared ultrastructurally to show the value of electron microscopy in subtyping these neoplasms. Both were subcutaneous, case 1 occurring in the nasolabial fold and case 2 in the upper calf. Both consisted of fascicles of spindle cells, and both stained positively for vimentin and alpha-smooth muscle actin; only case 2 stained additionally for desmin. Case 1 showed strong and case 2 weak or negative staining for fibronectin. By electron microscopy, case 1 contained prominent rough endoplasmic reticulum, peripheral fine filaments with focal densities, and fibronexus junctions. By contrast, case 2 was characterized by an external lamina and well-developed bundles of fine filaments with focal densities. Case 2 was considered a typical leiomyosarcoma, and case 1 was interpreted as showing myofibroblastic differentiation. The nomenclature for these myofibroblastic tumors is discussed, and myofibrosarcoma and leiomyosarcoma, myofibroblastic variant are suggested as suitable terms.

Adenoid cystic carcinoma of the skin--an immunohistochemical and ultrastructural study.

Adenoid cystic carcinoma of the skin was studied. Histologically, tumor cells were arranged in a tubular and a cribriform pattern, mainly int he reticular dermis. Immunohistochemically, epithelial membrane antigen was reactive with the tumor cells, but S-100 protein, vimentin, and carcino-embryonic antigen were not. On electron microscopy, we confirmed the findings of previous reports; tumor cells were arranged to form luminal structures; most of them were pseudolumina containing fine mucin granules, basal laminae, and collagen fibers, but some were true lumina with numerous microvilli and junctional complexes. New findings of this study were bizarre-shaped, electron-dense, net-like structures within the true lumina which were considered to be a type of mucin.

Signet ring cell basal cell carcinoma.

A 63-year-old man presented with a signet ring cell basal cell carcinoma of the right infraorbital area. This is the third reported case of this rare variant of basal cell carcinoma characterized by tumor cells containing large, hyalinized, eccentric, intracytoplasmic inclusions that compress nuclei into crescent or ring-shaped forms. Antibodies to both high and low molecular weight cytokeratins were strongly positive, staining the inclusions in a uniform fashion. Vimentin and actin antibodies did not stain the inclusions. These results support previous electron microscopic studies that show the inclusions to be aggregates of intermediate filaments blending into tonofilaments at their periphery. Although speculative, the formation of signet ring cells does not appear to be a degenerative or necrotic phenomenon, but probably a peculiar aberrant form of individual cell keratinization.

Multiple rhabdomyomatous mesenchymal hamartomas of skin.

A case of multiple rhabdomyomatous mesenchymal hamartomas is presented. The patient is a black male infant, the product of an uncomplicated term gestation and delivery. At birth, there were numerous polyps distributed over the periorbital and periauricular areas bilaterally. Some appeared fingerlike with constrictions below their tips. Others were branched or globular in shape. These projections showed spontaneous and independent movement, particularly during feedings. On histopathologic examination, the polyps were covered by squamous epithelium and contained normal follicular units. Bundles of skeletal muscle were present in the reticular dermis, extending into the subcutis. Regular cross-striations were seen in these muscle fibers. In some specimens, the muscle bundles formed a solid, central core. Skeletal muscle histochemical stains confirmed the presence of both types 1 and 2 muscle fibers. Electron microscopy revealed a normal skeletal muscle banding pattern. This case is the first report of multiple rhabdomyomatous mesenchymal hamartomas of skin. Functional skeletal muscle with spontaneous movement is part of the clinical picture.

Desmoplastic trichoepithelioma nosology. Reappraisal about a case developed on a varicella scar.

We report the case of a 51-year-old woman who presented with a progressive elevation of the border of an old varicella scar. The lesion which was clinically diagnosed as a basal cell carcinoma turned out to be a typical desmoplastic trichoepithelioma. The development of desmoplastic trichoepithelioma in an area of scarring has not been previously reported. The nosology of this tumor is discussed with particular emphasis on its possible relationship to morphoeic basal cell carcinoma, thus questioning it as a true tumor sui generis.

Congenital primitive neuroectodermal tumor with epithelial and glial differentiation. An ultrastructural and immunohistochemical study.

A congenital primitive neuroectodermal tumor associated with epithelial and glial elements is described. This soft-tissue tumor present on the right temple of a newborn boy consisted mainly of small round cells of the primitive neuroepithelial type, occasionally forming rosettes. The other components were focal glandular structures producing mucin, and aggregates of epithelioid cells bearing clear cytoplasm, both being distributed throughout the entire tumor. Additional glandular and clear cell components were strongly positive for various epithelial markers, such as carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin. Epithelioid cells were also positive for neuron-specific enolase and S100 protein. Glial differentiation was evidenced in some of the epithelioid cells by localization of cytoplasmic glial fibrillary acidic protein. These findings suggest that this tumor derives from a remnant of a neural crest, and the possibility of a special type of peripheral primitive neuroectodermal tumor is considered.

Type VII collagen is a component of cylindroma basement membrane zone.

Cylindroma basement membranes (BMs) were studied by electron microscopy and immunofluorescence with antibodies to Types IV and VII collagen in order to correlate the ultrastructure with the biochemical characteristics. Type IV collagen served as a marker for lamina densa structures and Type VII collagen for the anchoring fibrils. Ultrastructurally, the cylindroma BMs were composed of a wide band of BM-like material in which numerous anchoring fibrils were embedded. The BMs surrounding the tumor cell clusters and nodules of BM-like material entrapped within the tumor cell islands stained positively for both Types IV and VII collagen. We conclude, that anchoring fibrils are a major component of cylindroma BM zone. A trichoepithelioma investigated as control showed a BM similar to the one found at the dermoepidermal junction, i.e. a BM distinctly different from the one of cylindroma. The trichoepithelioma BMs and nodules of BM-like material included within the tumor also stained positively for both Type IV and VII collagen.

Rippled-pattern trichomatricoma. Histological, immunohistochemical and ultrastructural studies of an immature hair matrix tumor.

A hair matrix tumor showing an unusual tumor cell arrangement was found at the base of a solitary trichoepithelioma. Coexisting with solid epithelial islands and immature hair follicle-like stroma resembling the Verocay bodies of neurilemmoma or "ripplemarks" on waves were found. In other areas myxomatous degeneration of the stroma changed the rippling into a cribriform pattern. In some parts of the tumor there was a dense melanin pigment associated with MEL5 stained melanocytes. S-100 and CD1 (OKT6) antigen stains demonstrated Langerhans cells scattered in the parenchyma and less frequently in the stroma. The majority of tumor cells were considered immature pilar cortical cells because of the following: 1. HKN-6 was strongly positive; 2. a large number of melanocytes were associated with tumor cells in some foci; 3. ultrastructurally immature tumor cells, which had electron-dense tonofilaments and many desmosomes, were transformed without production of trichohyalin granules into semikeratinized cells which showed nuclear degeneration and loss of electron density in tonofilaments. This tumor, however, has not attained the degree of differentiation observed in trichoblastoma (1) another example of an immature cortical cell tumor. Squamous eddy-like or horn pearl-like foci of incomplete keratinization and large keratin-filled cysts were also present within the immature parenchyma, indicating that some immature cells were differentiating toward non-cortical cells, as found in the outer sheath. We would like to designate this tumor "rippled pattern trichomatricoma", a new entity.

Clear cell carcinoma of the skin: a tricholemmal carcinoma?

We report the light and electron microscopic findings of an unusual, locally aggressive cutaneous clear cell carcinoma involving extensively the left cheek and upper lip of a 61-year-old woman. The patient remained free of recurrence 5 years after wide local excision. Microscopically, the tumor was a poorly circumscribed and deeply invasive clear cell neoplasm characterized by large lobules and convoluted trabeculae of polygonal and columnar cells with palisading of the peripheral cells rimmed by thick basement membranes, and horn microcysts with tricholemmal keratinization. The tumor infiltrated the muscle and the salivary glands. Only slight cytologic atypia and a few mitotic figures were present. No definite ductal differentiation was found. Immunoperoxidase staining for carcinoembryonic and epithelial membrane antigens was negative. Ultrastructurally, the tumor cells were joined by desmosomes, and surrounded by thick basal lamina. The cytoplasm contained large pools of glycogen. Peculiar whorls of tonofilaments and aggregates of needle-shaped and club-shaped structures were observed in a small keratinizing focus. The tumor showed features resembling the outer root sheath of the hair follicle microscopically. Furthermore, the lack of duct-like structures and immunoreactivity of carcinoembryonic antigen tend to favor tricholemmal over sweat gland differentiation in this tumor which possibly represents a rare example of tricholemmal carcinoma.

Hemangiopericytoma arising in a solitary plexiform neurofibroma: report of a case and review of the literature.

A 71-year-old black woman with no known stigmata of neurofibromatosis developed a left buccal mass of 2 years duration. Histologic findings revealed a hemangiopericytoma and a plexiform neurofibroma in the same tumor. Cells with features of both tumor components were demonstrated ultrastructurally.