Connie A. Keehn

Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisal

Background:  Cutaneous tumor metastasis may be the first manifestation of cancer, but more often is a harbinger of advanced disease that portends an ominous prognosis. All skin accessions over the past 10 years from a large Veterans Administration (VA) hospital were reviewed.

Histopathology of cutaneous squamous cell carcinoma and its variants.

Squamous cell carcinoma is the second most common type of skin cancer, causing approximately 2,500 deaths in the United States each year. The principle risk factor for its development is ultraviolet light exposure. Conventional clinical and pathologic attributes of this neoplasm include an ulcerating papule located in a sun-exposed site with histologic sections showing an infiltrating neoplasm comprised of keratinizing epithelioid cells. Several histologic variants of squamous cell carcinoma with distinctive clinical and pathologic attributes including Bowens disease, keratoacanthoma, acantholytic, spindle cell, desmoplastic, and verrucous and pigmented types have been described and are the topic of discussion in this article.

The diagnosis, staging, and treatment options for mycosis fungoides.

BACKGROUND Cutaneous T-cell lymphoma (CTCL) represents a spectrum of diseases composed of malignant T lymphocytes. The most common type is mycosis fungoides (MF). An accurate diagnosis of early MF may be difficult because of the varied clinical and histologic expressions of the disease. METHODS The authors review the epidemiology, possible risk factors, clinical manifestations, diagnostic techniques, staging, prognosis, and treatment options for MF. RESULTS The varied and often nonspecific clinical and histologic presentations of MF may delay diagnosis and staging, thus necessitating further studies such as immunophenotyping and T-cell receptor gene rearrangement analysis. CONCLUSIONS A multidisciplinary approach to the diagnosis, staging, and treatment of MF assists in optimizing outcomes from management of patients with this disease.

CD-10 immunostaining differentiates superficial basal cell carcinoma from cutaneous squamous cell carcinoma.

Basal cell carcinoma and squamous cell carcinoma are common entities in clinical practice. Their distinction can be difficult clinically as well as histologically. CD10 or common acute lymphoblastic leukemia antigen (CALLA) is a metallomembrane endopeptidase expressed on a variety of normal and neoplastic cells. We sought to determine if the CD10 immunostain could have diagnostic utility in distinguishing between early superficial basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). CD10 was strongly expressed in 14 out of 14 superficial BCCs and failed to express in 2 out of 2 deeply infiltrative BCCs. CD10 was negative in the tumor cells in 13 out of 13 superficially invasive SCCs and SCC in situ. CD10 expressed weakly in the surrounding stromal cells of 2 out of 13 SCCs. These findings support the utility of CD10 as a marker for early BCC, especially when SCC cannot be excluded clinically or by conventional stains. Furthermore, these results implicate CD10 in the pathogenesis of BCC.

Expression of the Ets-1 Proto-Oncogene in Melanocytic Lesions

Ets-1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up-regulation of Ets-1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in melanocytic lesions. A series of 10 cutaneous melanomas and 24 benign melanocytic lesions with patient records were independently examined for diagnosis confirmation and immunohistochemical expression by two dermatopathologists. The immunohistochemical expression for Ets-1 (Novocastra, Newcastle upon Tyne, UK) was scored by an average of the mean labeling intensity; no nuclear staining = 0, weak nuclear staining = 1, moderate = 2, and intense = 3. Ets-1 expression was statistically assessed by the one-way analysis of variance (ANOVA) comparing the mean labeling intensity of melanoma to benign melanocytic nevi. All of the benign melanocytic lesions exhibited negative to weak nuclear staining, with an average mean labeling intensity of 0.4. Melanoma in situ exhibited moderate nuclear staining, for a mean labeling intensity of 2.0, whereas all conventional invasive melanomas exhibited moderate to strong nuclear staining, with a mean labeling intensity of 2.7. Metastatic melanoma exhibited very strong nuclear staining, with a mean labeling intensity of 3.0. Invasive desmoplastic melanoma, like melanoma in situ, showed moderate nuclear staining with a mean labeling intensity of 2.1. There was a trend toward more intense staining with melanoma progression. A statistically significant difference in the mean labeling intensity of Ets-1 was seen between invasive melanoma and benign melanocytic nevi (P < .0001). Ets-1 oncoprotein expression, however, does not distinguish among benign melanocytic lesions. Staining intensity and pattern might be a useful adjunct with histomorphology in distinguishing invasive melanoma from benign melanocytic nevi. Furthermore, Ets-1 expression may be an important pathogenic mechanism and predictor of aggressive biologic behavior of cutaneous melanoma, with a trend toward staining intensity increasing as Clark stage increases.

Ets-1 immunohistochemical expression in non-melanoma skin carcinoma

Background:  Ets‐1 oncoprotein is a transcription factor known to regulate the expression of numerous genes important in extracellular matrix remodeling and angiogenesis. Up‐regulation of Ets‐1 has been shown to be important in a variety of human malignancies and to correlate with prognosis. To our knowledge, this oncoprotein has not been examined in non‐melanoma skin carcinomas.

Verrucous psoriasis : A distinctive clinicopathologic variant of psoriasis

Psoriasis is capable of presenting in a variety of clinical and pathologic guises including a rarely described variant variably termed hypertrophic or verrucous psoriasis. Herein, we describe the clinical and pathologic attributes of a large series of patients with this unusual variant of psoriasis and distinguish it from other entities in the differential diagnosis. The histopathologic features and clinical and demographic attributes of a series of 12 cases from 12 patients were reviewed by a single dermatopathologist (MM). The 12 patients consisted of 7 males and 5 females with an average age of 61.8 years (males 38-93 years, females 41-71 years). Eight of the patients were Caucasian, 3 Hispanic and 1 African-American. Six of the lesions were located on the knees, 4 involved the elbows, and 2 were seen on the dorsum of the hands (metacarpal-phalangeal joint). The clinical appearance of the lesions consisted of flesh-toned to white mammillated plaques (8 cases) and coalesced papules (4 cases). Each of the biopsies showed regular psoriasiform epidermal hyperplasia with acanthosis, hyperkeratosis, and either spongiform neutrophilic or Munro micro-abscesses. In addition, each showed papillomatosis with bowing of the peripheral rete ridges toward the center of the lesion (buttressing). At high power, epidermal neutrophils were seen in particular surmounting the tips of the suprapapillary plates with accompanying serum. Hypergranulosis and koilocytic change were not observed in any of the lesions. Human papilloma virus (HPV) immunostaining and periodic acid Schiff (PAS) special staining for fungi were negative. Verrucous psoriasis is a distinctive variant of psoriasis with overlapping clinical and pathologic features that might prompt consideration of verruca vulgaris. The presence of epidermal papillomatosis and epidermal buttressing seen in these lesions is reminiscent of the histologic features of verruca vulgaris. Similarly, the presence of coalesced papules might prompt clinical consideration of verruca vulgaris as well. It is likely that this under recognized clinicopathologic entity represents a patterned response of the epithelium to repeated trauma/irritation typical of the anatomic locations that were encountered in this series. Recognition of this entity should preempt confusion with verruca vulgaris or other entities capable of producing wart-like epidermal changes.

Subepidermal blistering disorders: A clinical and histopathologic review

The subepidermal blistering disorders are comprised of a number of unrelated disorders with a diverse clinical presentation and pathogenic basis that share in common the presence of blister formation beneath the epidermis. Many of the disorders are both debilitating and potentially fatal. Timely and accurate diagnosis facilitates their appropriate management. The etiologic, clinical, and pathologic attributes as well as the treatment of these disorders including bullous pemphigoid, epidermolysis bullosa acquisita, dermatitis herpetiformis, linear IgA dermatosis, cicatricial pemphigold, herpes gestationis,and porphyria cutanea tarda are described.

Expression of insulin-like growth factor-I receptor in primary cutaneous carcinomas

Background:  Insulin‐like growth factor‐I (IGF‐I) is the principal mediator of growth hormone, exerting its effects through binding of the insulin‐like growth factor‐I receptor (IGF‐IR). Post‐receptor activation leads to the production of transcription factors involved in cell proliferation, differentiation, transformation, and survival. Data indicate that IGF‐IR is involved in tumorigenesis. To our knowledge, this receptor has not been previously studied in primary cutaneous carcinomas.

Hamartin and tuberin immunohistochemical expression in cutaneous fibroepithelial polyps

Background:  Hamartin and tuberin are inactivating tumor suppressor proteins implicated in the development of gastrointestinal polyps and sporadic and tuberous sclerosis‐associated cutaneous angiofibromas. The pattern of expression of these peptides has not been studied in fibroepithelial polyps (FEPs).