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Phillip H McKee

Publications and source records attributed to Phillip H McKee.

11 recordsLinked to original sources
PubMed2006

Amplification of CDK4 and MDM2 in malignant melanoma.

Amplification of the 12q13-15 region is a common event in several human tumors including liposarcomas, gliomas, and osteosarcomas. We have demonstrated high-level amplification of 12q14 in a subset of uncultured malignant melanomas (3 of 53). High-resolution mapping of the amplicon using quantitative PCR revealed a bipartite amplicon consisting of a primary 50-kb amplicon centered on CDK4 and a secondary amplicon centered on MDM2, without amplification of the intervening 11 Mb of genomic DNA. Analysis of mRNA and protein levels in melanomas with 12q14 amplification demonstrated overexpression of target genes CDK4 and MDM2 without loss of CDKN2A-P16 (P16INK4A) or CDKN2A-P14ARF (P14ARF) expression, important regulators of the RB1 and TP53 pathways, which are commonly lost or mutated in melanoma. These results suggest that coamplification of CDK4 and MDM2 may substitute for loss of P16INK4A and P14ARF function in a subset of melanomas.

Chromosomes, Human, Pair 12↗
PubMed2005

Pilomatrix carcinomas contain mutations in CTNNB1, the gene encoding beta-catenin.

Mutations in beta-catenin are present in benign pilomatrixomas. beta-catenin is a downstream effector in the WNT-signalling pathway, acting as a signal for differentiation and proliferation. Mutations in CTNNB1, the gene encoding beta-catenin, are present in a wide variety of benign and malignant neoplasms. We examined beta-catenin in a series of pilomatrix carcinomas (15 cases) by using immunohistochemistry and DNA sequencing of exon 3 from CTNNB1, and compared these to a series of benign pilomatrixomas (13 cases). All 11 pilomatrix carcinomas available for examination showed nuclear localization of beta-catenin and mutations in exon 3 similar to those demonstrated in benign pilomatrixomas. Two of 11 pilomatrix carcinomas showed significant nuclear accumulation of p53, whereas this was absent in all 13 benign pilomatrixomas. Expression of nuclear cyclin D1 was similar in both benign pilomatrixomas and pilomatrix carcinomas. Clinical follow-up from the 15 malignant cases reported in this study and by others indicates that wide excision offers superior control of local recurrence, compared to simple excision. Immunohistochemical and molecular analysis of beta-catenin reveals that both pilomatrix carcinomas and benign pilomatrixomas harbour mutations in beta-catenin. This implies a common initial pathogenesis and is compatible with the proposition that pilomatrix carcinomas may at least on occasion arise from their benign counterparts.

Adolescent↗
PubMed2005

Basal cell carcinoma with matrical differentiation: a case study with analysis of beta-catenin.

Matrical differentiation in basal cell carcinoma (BCC) is rare. Only nine cases have been described that showed typical diagnostic features of BCC, in addition to shadow cells indicating hair-matrix differentiation. These cases often present a diagnostic challenge due to confusion with pilomatrixoma or pilomatrix carcinoma. We present a case of BCC with matrical differentiation in a 78-year-old man. Immunohistochemical and molecular methods are used to differentiate this lesion from benign or malignant forms of pilomatrixoma. differentiation: a case study with analysis of beta-catenin.

Aged↗
PubMed2004

Tissue eosinophils and the perils of using skin biopsy specimens to distinguish between drug hypersensitivity and cutaneous graft-versus-host disease.

Graft-versus-host disease (GvHD) is a frequent and serious complication of bone-marrow transplantation (BMT), and carries a high morbidity and mortality if not promptly recognized and treated. The rash of acute GvHD is often difficult to distinguish clinically from a drug eruption, and skin biopsies are often performed in an attempt to render a diagnosis. Histologically, eosinophils are classically associated with hypersensitivity reactions, and their presence in inflamed tissue is considered suggestive of a drug-induced dermatitis. We present 3 cases of acute exanthema in BMT recipients in whom the presence of eosinophils on skin biopsy specimen led to an initial diagnosis of drug eruption over GvHD. As a result, these patients experienced delays in the institution of definitive immunosuppressive therapy for GvHD. We review the growing literature suggesting that no single or combined histologic feature, including tissue eosinophils, is useful in differentiating GvHD from drug eruptions in BMT recipients. Indeed, in most cases, the cause of a new-onset blanchable erythematous rash in a BMT recipient is most accurately determined by close examination and follow-up of the clinical features without a skin biopsy.

Adult↗
PubMed2003

Co-expression of p16(INK4A) and laminin 5 gamma2 by microinvasive and superficial squamous cell carcinomas in vivo and by migrating wound and senescent keratinocytes in culture.

The high frequency of mutation, deletion, and promoter silencing of the gene encoding p16(INK4A) (p16) in premalignant dysplasias and squamous cell carcinomas (SCC) of epidermis and oral epithelium classifies p16 as a tumor suppressor. However, the point during neoplastic progression at which this protein is expressed and presumably impedes formation of an SCC is unknown. Induction of p16 has been found to be responsible for the senescence arrest of normal human keratinocytes in culture, suggesting the possibility that excessive or spatially abnormal cell growth in vivo triggers p16 expression. We examined 73 skin and oral mucosal biopsy specimens immunohistochemically to test this hypothesis. p16 was not detectable in benign hyperplastic lesions, but instead was expressed heterogeneously in some dysplastic and carcinoma in situ lesions and consistently at areas of microinvasion and at superficial margins of advanced SCCs. p16-positive cells in these regions coexpressed the gamma2 chain of laminin 5, identified previously as a marker of invasion in some carcinomas. Normal keratinocytes undergoing senescence arrest in culture proved to coordinately express p16 and gamma2 and this was frequently associated with increased directional motility. Keratinocytes at the edges of wounds made in confluent early passage cultures also coexpressed p16 and gamma2, accompanying migration to fill the wound. These results have identified the point during neoplastic progression in stratified squamous epithelial at which the tumor suppressor p16 is expressed and suggest that normal epithelia may use the same mechanism to generate non-dividing, motile cells for wound repair.

Animals↗
PubMed2003

Myelogenous leukemia cutis resembling stasis dermatitis.

Leukemia cutis may clinically mimic many inflammatory dermatoses. A patient with myelodysplastic syndrome presented with an acute eruption of bilateral, lower-extremity, tender, indurated, brown plaques that clinically resembled chronic stasis dermatitis. Histologic study revealed a dermal myeloblastic leukemic infiltrate.

Dermatitis↗
PubMed2003

Childhood bullous pemphigoid: a clinicopathologic study and review of the literature.

Bullous pemphigoid (BP) is an acquired bullous disorder that predominantly affects the elderly. It is rare in children but when it occurs, there is considerable clinical and histologic overlap with other acquired or congenital blistering disorders. A definitive diagnosis of childhood BP requires direct immunofluorescence and, in some cases, characterization of the target antigen. Three cases of childhood BP are presented, with their histologic and immunofluorescence findings. The first was a 5-month-old male infant who presented with erythema and bullae of the palms and soles and was found to have linear deposition of IgG and C3 along the dermoepidermal junction on direct immunofluorescence (DIF). Histopathologic examination revealed a subepidermal blister containing eosinophils. Type IV collagen was demonstrated along the floor of the blister cavity by a direct immunoperoxidase technique. The second case was an 8-month-old female infant who presented with a blistering eruption of her palms and soles that then became widespread. Direct immunofluorescence showed linear IgG and C3 at the dermoepidermal junction, with laminin deposition at the base of the blister. The third case was a 7-year-old female with bullae and erosions on the vulva and vaginal mucosa. A subepidermal blister was seen on microscopic examination whereas immunofluorescence demonstrated linear IgG and C3 deposition at the basement membrane zone (BMZ). A literature review uncovered 50 cases of childhood BP confirmed by direct or indirect immunofluorescence, or both, and often with evidence of autoantibodies against either the 180 kD or the 230 kD human bullous pemphigoid antigens (BP180 or BP230). This review was used to delineate characteristics of childhood BP, including the newly proposed subtypes: infantile BP and childhood localized vulval BP. Infantile BP presents within the first year of life and is characterized by BP-like lesions on erythematous or normal acral skin. Localized vulval BP is a self-limited, nonscarring BP-like process that involves only the vulva. Both subtypes are normally self-limited and respond well to either topical or systemic steroids, if treatment is initiated before the disease becomes widespread.

Administration, Topical↗
PubMed2002

Cutaneous rosai-dorfman disease is a distinct clinical entity.

Rosai-Dorfman disease (RDD) is a rare but distinctive clinicopathologic entity of unknown etiology affecting lymph nodes as well as extranodal sites. Although cutaneous involvement in RDD is common, purely cutaneous disease is rare and not well documented. We report 22 patients with cutaneous and superficial subcutaneous RDD. The lesions presented as papules and nodules, often with discoloration (9/22) and frequent multifocality (13/22), without predilection for a specific site of the body. Age distribution was wide and ranged from 15 to 68 years, with a median of 43.5 years. Of the 17 patients for whom information on racial background was available, 7 were Asian, 8 were white, and 2 were black, with a marked female predominance (2:1). The lesions resolved in 6 of 13 patients for whom follow-up data were available, regardless of the treatment given. Lesions persisted or recurred in 7 patients. Histologically, the lesions are invariably characterized by a proliferation of polygonal S100-positive histiocytes showing emperipolesis and a mixed inflammatory infiltrate. This study characterizes the histologic spectrum of cutaneous RDD in regard to variation in the numbers of typical S100-positive histiocytes and emperipolesis, variation in the quality and quantity of the inflammatory response, and the degree of stromal fibrosis, which resulted in a strikingly storiform growth pattern in six lesions and a lobulated pattern in two lesions. Whereas the clinical as well as histologic appearance of the cutaneous and subcutaneous lesions in the purely extranodal forms of RDD is indistinguishable from that of systemic RDD, this study emphasizes that purely cutaneous RDD is a distinct clinical entity in regard to its epidemiology and remains localized to the skin even with long-term follow-up. Patients with purely cutaneous RDD are of an older age at onset of disease (median = 43.5 years), with a reversed male/female ratio. There are no significant systemic extracutaneous or serologic manifestations. Whereas systemic RDD is commonly seen in blacks and only rarely reported in Orientals, the majority of the patients in this series with purely cutaneous RDD are Asians and whites.

Adolescent↗
PubMed2002

Amelanotic cellular blue nevus: a hypopigmented variant of the cellular blue nevus: clinicopathologic analysis of 20 cases.

Blue nevus and its variants typically present as pigmented lesions. Dermal melanin is responsible for coloration and is an expected histologic finding. Herein, we report 20 cases of an unusual amelanotic variant of cellular blue nevus. Our series showed clinical demographics similar to pigmented counterparts. Thus, there was a predilection for young individuals with a mean age of 24 years (range 6-74 years). Both sexes were affected, with a female-to-male ratio of approximately 2:1. The lower back, distal extremities, and scalp were the most common sites of occurrence. Importantly, the lack of pigmentation resulted in an atypical clinical appearance. A diagnosis of blue nevus by the attending physician was not considered in any of the reported lesions. All of the tumors extended deep into the reticular dermis or subcutaneous fat with a mean thickness of 5.5 mm (range 1.7-11 mm). Ulceration was present in two lesions. Mild cytologic atypia and pleomorphism were present in five cases. Mitotic activity (up to 3 mitoses/mm ) was observed in 11 lesions. A brisk lymphocytic host response was present in only one lesion. Tumor necrosis was not observed. Most, but not all, tumors showed reactivity for S-100 and HMB-45. Clinical follow-up (mean 32 months) was consistent with a benign course. Local recurrence was not observed after complete excision. None of the cases was associated with clinical evidence of lymph node or distant metastases. Recognition of amelanotic cellular blue nevus is important because the lack of expected pigmentation may result in clinical and pathologic diagnostic difficulty. In particular, amelanotic cellular blue nevus must be distinguished from malignant cellular blue nevus and other variants of melanoma.

Adolescent↗
PubMed2002

Cutaneous T-cell lymphoproliferative disorders: approach for the surgical pathologist: recent advances and clarification of confused issues.

Cutaneous T-cell lymphoproliferative disorders (CTCLs) remain a subject of confusion and controversy. In this review, the authors discuss diagnostic criteria and classification, including the role of immunohistochemistry and gene rearrangement studies. In addition, cutaneous T-cell pseudolymphomas, the current status of parapsoriasis and other premalignant syndromes, and the clinicopathological variants of mycosis fungoides are discussed. CD30-positive lymphoproliferative disorders and a number of rare variants of CTCL including granulamatous slack skin, subcutaneous (panniculitic) T-cell lymphoma, gamma-delta cutaneous lymphoma, NK/NK-like T-cell lymphoma, and primary cutaneous CD8-positive epidermotropic cytotoxic T-cell lymphoma are also considered.

Gene Rearrangement↗