Terence J. Harrist

The malignant potential of small congenital nevocellular nevi: An estimate of association based on a histologic study of 234 primary cutaneous melanomas

In order to assess a relationship between small congenital nevocellular nevi and cutaneous melanoma, histologic features commonly associated with congenital nevi were sought in 234 melanomas. The detection of one or more histologic features of congenital nevi in 8.1% (19/234) of melanoma specimens was directly related to the number of slides and tissue sections with melanoma available for review, the predominance of superficial spreading melanoma (SSM) and the historic relationship to a preexisting pigmented nevus at the tumor site. The histologic association was inversely related to melanoma thickness and tumor location on the lower extremities. The observed frequency of histologic association was estimated to be approximately 4,000 to 13,000 times greater than expected on the basis of surface area by chance alone. These findings suggest that small congenital nevi may be precursors for at least some cases of cutaneous melanoma. The strength of histologic association is highly dependent on the specificity of methods used for detecting congenital nevi in melanoma specimens.

Mucocutaneous lentigines, cardiomucocutaneous myxomas, and multiple blue nevi: The “LAMB” syndrome

We describe a 13-year-old girl with a cardiocutaneous syndrome characterized by an atrial myxoma, pigmented lesions of the skin and genital mucosa, and opalescent papules and dermal nodules of the skin and tongue. Her pigmented lesions included black macules of the face and vulva, brown macules of the lips and perioral skin, multiple blue nevi, and a congenital nevomelanocytic nevus. The black and brown macules of the face and vulva consisted of lentiginous proliferations of large, intensely dopa-reactive melanocytes. The opalescent papules and dermal nodules had histologic, ultrastructural, and histochemical characteristics of myxomas. During follow-up, the patient developed thyroid nodules, which were composed of mixed papillary and follicular hyperplasia. This case emphasizes the necessity of a cardiac evaluation for a potentially fatal (and surgically treatable) atrial myxoma in individuals with multiple melanocytic and myxomatous tumors of the skin and mucosa.

Dysplastic melanocytic nevi in histologic association with 234 primary cutaneous melanomas

Dysplastic melanocytic nevi (DMN) are irregularly pigmented lesions characterized by (1) atypical melanocytic hyperplasia in a lentiginous epidermal pattern (AMHL), (2) one or more dermal mesenchymal changes, and (3) frequently a dermal nevocellular nevus. In order to determine an association between DMN and cutaneous melanoma, the dominant histologic feature of DMN (namely, AMHL) was sought in histologic contiguity with 234 primary melanomas. Of these 234 cases, 9 were lentigo maligna melanomas. Of the remaining 225 cases, 49 (21.8%) were associated with AMHL in the same histologic section as (but beyond the most lateral margin of) intraepidermal and invasive melanoma. AMHL was directly associated with the presence of dermal nevocellular nevi in histologic contiguity with melanoma, and a greater number of histologic slides with melanoma available for review. AMHL was inversely associated with nodular melanoma. Most of the AMHL cases were not associated with familial melanoma, but the total number of familial cases was low. The histologic association between AMHL and melanoma in one fifth of cases in this series supports the hypothesis that at least some cutaneous melanomas may have an origin in DMN.

T cell subsets and Langerhans cells in lichen planus: in situ characterization using monoclonal antibodies.

Skin biopsies from four patients with lichen planus were studied using monoclonal antibodies directed against T lymphocytes. Anti‐T1 and anti‐T3 antibodies, which react with all peripheral T cells, stained most cells in the dermal infiltrates. The majority of infiltrating cells also stained with anti‐T4 and anti‐T4b antibodies, which react with helper/inducer cells, whereas a minority of cells stained with anti‐T8 antibody, which reacts with cytotoxic/suppres‐sor cells. Surface IgM was not identified on any infiltrating cells, providing evidence against B cell participation. Intraepidermal and dermal cells with long cytoplasmic extensions stained with anti‐T6 antibody in all cases, defining them as Langerhans cells or their precursors. T6‐positive cells were seen in greater number than in normal control epidermis and dermis. The results indicate that well‐developed lesions of lichen planus are characterized by an influx of helper/inducer T lymphocytes and increased numbers of Langerhans cells. These observations support the contention that cellular immunity is important in the pathogenesis of this disorder.

Prognostic Factors for Patients with Clinical Stage I Melanoma of Intermediate Thickness (1.51–3.99 mm)* A Conceptual Model for Tumor Growth and Metastasis

Fourteen variables were tested for their ability to predict visceral or bony metastases in 177 patients with clinical Stage I melanoma of intermediate thickness (1.51–3.99 mm). A Cox multivariate analysis yielded a combination of four variables that best predicted bony or visceral metastases for these patients: 1) mitoses > 6/mm2 (p = 0.0007), 2) location other than the forearm or leg) p = 0.009), 3) ulceration width > 3 mm (p = 0.04), and 4) microscopic satellites (p = 0.05). The overall prognostic model chi square was 32.40 with 4° of freedom (p < 10-5). Combinations of the above variables were used to separate these patients into at least two risk groups. The high risk patients had at least a 35% or greater chance of developing visceral metastases within five years, while the low risk group had greater than an 85% chance of being disease free at five years. Criteria for the high risk group were as follows: 1) mitoses > 6/mm2 in at least one area of the tumor, irrespective of primary tumor location, or 2) a melanoma located at some site other than the forearm or leg and histologic evidence in the primary tumor of either ulceration > 3 mm wide or microscopic satellites. The low risk group was defined as follows: 1) mitoses ≤ 6/mm2 and a location on the leg or forearm, or 2) mitoses ≤ 6/mm2 and the absence in histologic sections of the primary tumor of both microscopic satellites and ulceration ≥ 3 mm wide. The number of patients in this series who did not undergo elective regional node dissection (N = 47) was probably too small to detect any benefit from this procedure. Based on survival rates from this and other studies, it is estimated that approximately 1500 patients with clinical Stage I melanoma of intermediate thickness in each arm of a randomized clinical trial would be needed to detect an increase in survival rates from elective regional node dissection.

“Microscopic satellites” are more highly associated with regional lymph node metastases than is primary melanoma thickness

A multivariate analysis was performed on 20 clinical and histologic variables from 327 Stage I prospectively studied melanoma patients who underwent elective regional lymph node dissection (ERLD). Primary tumor thickness, microscopic satellites, and the elapsed interval between diagnosis and ERLD, were selected as the combination of variables that were most highly associated with clinically occult regional lymph node metastases (P = 10−15, model chi‐square). Microscopic satellites were defined as tumor nests, >0.05 mm in diameter, in the reticular dermis, panniculus, or vessels beneath the principal invasive tumor mass but separated from it by normal tissue on the section in which the Breslow measurement was taken. The probability of finding nodal metastases for melanomas <0.75 mm thick was 0% (0/41 patients); for those 0.76–1.50 mm, 4% (4/108); 1.51–3.0 mm, 14% (14/102); and >3.0 mm, 39.5% (30/76). Primary melanomas >1.50 mm thick with microscopic satellites were more often associated with nodal metastases than those of similar thickness without satellites (30/57 (53%) versus 14/121 (12%), P = 0.01). Some satellites probably represent intraspecimen metastases, while others do not. Any predictive model for occult regional lymph node metastases based on data from ERLD done <50 days after diagnosis may underestimate the prevalence of metastases.

The PUVA-induced pigmented macule: A lentiginous proliferation of large, sometimes cytologically atypical, melanocytes

Eleven PUVA-induced pigmented macules (PM) obtained from seven psoriatic adults 4 to 6 years after starting PUVA therapy were compared to eight sun-induced pigmented macules (SM) and five specimens of light-protected skin (LPS) from twelve nonpsoriatic control subjects who had not received ultraviolet radiation therapy. Unlike SM, many PM were darkly or irregularly pigmented. In a blind histologic assessment using routine and L-dihydroxyphenylalanine (dopa)-incubated tissue sections, both PM and SM were lentigines. Three of eleven PM had slight melanocytic atypism, compared to none of eight SM. When compared to SM and LPS, PM had a significantly increased proportion of hypertrophic melanocytes. These observations demonstrate that chronic PUVA induces pigmented macules characterized by a lentiginous proliferation of large melanocytes which, in some cases, may be slightly atypical. PUVA-treated individuals require continual monitoring for atypical melanocytic lesions.

Neutrophilic eccrine hidradenitis: A distinctive rash associated with cytarabine therapy and acute leukemia

Neutrophilic eccrine hidradenitis (NEH) is a recently described neutrophilic dermatosis associated with acute myelogenous leukemia (AML) and chemotherapy. This disorder is a distinct clinicopathologic entity separate from leukemid reactions and other neutrophilic dermatoses. We describe two cases in which plaques or nodules developed in the second week after initiation of induction chemotherapy for AML. The lesions regressed in 1 week and recurred in one case when induction chemotherapy was given a second time. Histologically, the findings were similar in each case. Neutrophils palisaded about and infiltrated the eccrine coil in which necrosis of secretory epithelium was present. Focal mucinous degeneration of the eccrine adipose tissue cuff was the only other significant alteration. No vasculitis was observed. Cultures and histologic preparations for pathogenic organisms were negative. Cytarabine was the chemotherapeutic agent used in all three cases. NEH most likely represents either an unusual response caused by cytarabine or a manifestation of AML. Recognition of NEH is important in order to exclude other neutrophilic dermatoses associated with AML, such as sepsis and leukemia cutis, which may appear clinically similar.

In situ identification of T6‐positive cells in normal human dermis by immunoelectron microscopy*

Monoclonal anti‐T6 antibody, which reacts with the majority of cortical thymocytes but not peripheral T cells, also reacts with human epidermal Langerhans cells, as shown by a four‐step immunoperoxidase method and immunoelectron microscopy. To define whether T6‐positive cells are also present in normal human dermis, we used these techniques to demonstrate two immunologically distinct populations of histiocyte‐like cells in normal human dermis. The first population contains cells devoid of phagolysosomes or Birbeck granules. These cells react with anti‐T6 antibody, but not with monoclonal anti‐T3 antibody which defines peripheral T cells, and are found predominantly in and around dermal lymphatic vessels. The second is composed of phagolysosome‐containing cells which do not react with anti‐T6 antibody or anti‐T3 antibody.

Systematic underreporting of cutaneous malignant melanoma in Massachusetts: Possible implications for national incidence figures

An independent tabulation of incidence of cutaneous malignant melanoma in Massachusetts indicates that 12% and perhaps as many as 19% of new cases of cutaneous malignant melanoma in Massachusetts are not recorded in the Massachusetts Cancer Registry, significantly more than the expected 5% (p = 0.0001). The increasing number of nonhospital medical settings in which melanomas can be diagnosed and/or treated appears to account for this discrepancy. We suspect that these findings in Massachusetts also apply to cancer reporting systems in other regions of the United States. We suggest that the true incidence of cutaneous malignant melanoma in Massachusetts, and perhaps in the United States, may be significantly higher than reported.