Lucia Pozo

Critical Analysis of Histologic Criteria for Grading Atypical (Dysplastic) Melanocytic Nevi

Low concordance in grading atypical (dysplastic) melanocytic nevi (AMN) has been reported, and no systematic evaluation is available. We studied 123 AMN with architectural and cytologic atypia (40 associated with atypical-mole syndrome), classified according to standard criteria by 3 independent observers. Histologic variables included junctional and dermal symmetry, lateral extension, cohesion and migration of epidermal melanocytes, maturation, regression, nuclear features, nuclear grade, melanin, inflammatory infiltrate location, and fibroplasia. AMN (43 junctional and 80 compound) were graded mild (31), moderate (61), and severe (31). AMN-severe correlated with 3 or more nuclear abnormalities (especially pleomorphism, heterogeneous chromatin, and prominent nucleolus) and absence of regression, mixed junctional pattern, and suprabasilar melanocytes on top of lentiginous hyperplasia. AMN-severe diagnostic accuracy was 99.5% using these criteria, but only the absence of nuclear pleomorphism differentiated AMN-mild from AMN-moderate. No architectural features distinguishing AMN-mild from AMN-moderate were selected as significant by the discriminant analysis. AMN from atypical-mole syndrome revealed subtle architectural differences, but none were statistically significant in the discriminant analysis. Histologic criteria can reliably distinguish AMN-severe but fail to differentiate AMN-mild from AMN-moderate. AMN from atypical-mole syndrome cannot be diagnosed using pathologic criteria alone.

Malignant deep sclerosing blue naevus presenting as a subcutaneous soft tissue mass

not on antibiotics or G-CSF at the time. There was no improvement in the rash and a skin biopsy was performed. The skin biopsy revealed marked oedema of the upper dermis associated with a mild superficial perivascular chronic inflammatory infiltrate. The striking feature was the presence of a heavy infiltrate of neutrophils within the eccrine sweat glands in the deep dermis with focal gland destruction (Fig. 1b), consistent with the diagnosis of NEH. Stains for infectious agents were negative and no abnormal leukaemic infiltrates were seen. She was treated symptomatically with analgesia. The rash eventually resolved 10 days later upon recovery of her bone marrow function. The patient underwent four subsequent courses of consolidation treatment with high-dose cytarabine without recurrence of her rash. NEH is a rare and benign dermatosis which is self-limiting and usually resolves after 1–3 weeks. Recurrence with subsequent therapy can occur. The pathogenesis is uncertain but may be the direct consequence of the cytotoxicity of drugs secreted in the sweat on the eccrine gland, leading to tissue necrosis. This phenomenon may then induce chemotaxis of neutrophils. The important differential diagnosis clinically is Sweet’s syndrome, leukaemia cutis and cutaneous infection. In this case, skin biopsy findings excluded the latter two and the lack of fever and presence of severe neutropenia during the development of the rash makes Sweet’s syndrome unlikely. Although NEH developed in the classical setting in our patient, several features make this case unusual. NEH tends to occur in the setting of fever and is usually asymmetrical. Our patient was afebrile and had a striking symmetrical rash around both breasts without involvement of other areas of the skin. In a review of 51 published cases of NEH, the anterior chest was affected in nine cases (16%). Five of the patients had AML, two had Hodgkin’s disease, one had nephroblastoma and one had HIV infection. Five patients were men and four were women. The anterior chest is usually affected in the setting of more extensive involvement including other areas such as the trunk, limbs and face. Only one other case solely involving the breast was reported, in a 45-year-old woman with AML who presented with papules on her breast when severely neutropenic. In our patient, the rash was erythematous and raised in a symmetrical, circumferential distribution around both breasts with sparing of the nipple and the periareolar region. The localization of the rash was postulated to be due to differences in the metabolic secretory activity of the eccrine glands and additional local trauma, although this was not apparent in our patient. Although NEH is frequently asymptomatic, pain and discomfort can be a presenting symptom and was a striking feature in our patient. Furthermore, NEH is most often reported in caucasians. Only two Japanese patients and one Korean patient have been reported. Ours is the first Chinese patient reported. This case further highlights the polymorphic presentation of NEH. We suggest that NEH should be considered as a differential diagnosis in rashes that develop following chemotherapy for AML. Early recognition is important to avoid unnecessary drug therapy or drug cessation. A skin biopsy is usually diagnostic.

Cell proliferation in skin tumors with ductal differentiation: patterns and diagnostic applications

The kinetic features of skin tumors with ductal differentiation (TDD) remain mainly unknown. We selected 88 skin TDD (D‐PAS‐positive cuticles) classified according to Murphy and Elders criteria. Tumors studied included 13 poromas, 12 nodular hidradenomas, 10 cylindromas, 6 spiradenomas, 9 syringomas, 9 chondroid syringomas, 7 porocarcinomas, 15 malignant nodular hidradenomas, and 7 not otherwise specified carcinomas. The same tumor areas were evaluated for mitotic figure counting (MFC) and proliferation rate (PR=MIB‐1 index), screening 10 consecutive high‐power fields (HPFs) in the most cellular areas. Results were recorded by HPF and tumor cellularity, considering both average and standard deviation. Differences were analyzed by Students t‐test and analysis of variance (ANOVA) and considered significant if p<0.05. PR was significantly higher in malignant (23.29±12.49) than in benign tumors (3.86±4.44) and in poroma‐nodular hidradenoma (4.99±3.34) than in spiradenoma‐cylindroma‐syringoma (1.91±1.67), but not by malignant tumor type. MFC was significantly higher in malignant (25.52±4.10) than in benign tumors (1.57±0.38), showing porocarcinomas the biggest MFC/10 HPF and malignant nodular hidradenomas the highest MFC/1000 cells. PR and MFC are useful malignancy criteria in skin TDD and should be evaluated by tumor cellularity to avoid potential misinterpretations related with tumor heterogeneity.

Trichogerminoma: further evidence to support a specific follicular neoplasm.

Sir: A 74-year-old woman had developed a slowly growing lesion on the face over a period of 18 months, which became ulcerated and was excised with a clinical diagnosis of basal cell carcinoma. No enlarged lymph nodes, general symptoms, or evidence of distant tumour growth were present at the time of excision. The surgical specimen consisted of a 35 · 20 mm skin ellipse with soft tissue attached to a maximum depth of 10 mm. A 20-mm central ulceration with elevated margins was identified extending into the underlying soft tissue, which was replaced by dense white tissue. Histological examination revealed a well-circumscribed lesion invading the deep dermis, not connected with the superficial epidermis, and separated from the surrounding soft tissue by a thick capsule (Figure 1A). Perineural invasion but no vascular or lymphatic invasion was demonstrated at the periphery of the tumour. The intratumoral stroma showed hyalinized collagen and a focal desmoplastic reaction. Numerous trichilemmal-type keratinous microcysts were also identified throughout the neoplasm (Figure 1B). Central tumour cell necrosis resulted in a pseudopapillary growth pattern (Figure 1A), whereas viable tumour showed primitive cytological features with vesicular nuclei, prominent nucleoli and frequent mitotic figures (10–15 per 10 high-power fields), along with scattered catagen-like apoptotic bodies (Figure 1C). Adnexal neoplasm with follicular differentiation remains the most elusive diagnosis in dermatopathology, due to the variety of lesions and their relative low frequency. The diagnosis of adnexal neoplasm requires both consideration of the criteria for malignancy and evidence of pilar differentiation. They are generally benign and can be diagnosed in most instances at low magnification. General criteria for malignancy can be applied to all adnexal neoplasms, including infiltrative growth pattern, deep location, presence of necrosis and nuclear changes (hyperchromatism, pleomorphism, nucleolar enlargement, and mitotic figures). Pilar differentiation is suggested by the presence of hyalinized stromal changes [periodic acid–schiff (PAS) positive] around the epithelial nests, keratinous microcysts and ⁄ or cell ‘balls’ with or without peripheral nuclear palisading, catagen-like apoptotic bodies, and eosinophilic and clear cytoplasmic changes. A myxoid stroma containing CD34+ Figure 1. A, Basaloid cell proliferation invading the deep dermis and inducing a desmoplastic response. The tumour is separated from the surrounding dermis by a thick capsule (arrow). The inset reveals perineural invasion observed at the deep edges of the neoplasm. B, The tumour shows foci of necrosis, numerous mitotic figures, and trichilemmal-type keratinous cysts (arrows, suggesting pilar differentiation). Tumour cells reveal primitive features (inset). C, Primitive tumour cells reveal vesicular nuclei with prominent nucleoli and scant cytoplasms. Trichilemmal-type keratinous cysts, foci of necrosis, and catagen-like apoptotic bodies (arrow) are noted in this field.

Differential kinetic features by tumour topography in cutaneous small-cell neuroendocrine (Merkel cell) carcinomas

Background/Objectives  Merkel cell carcinomas (MCC) reveal epithelial and neuroendocrine differentiation, but its topographic cell kinetics remains unknown. This study analyses proliferation, apoptosis, and DNA ploidy by topography, features that can help planning therapeutic protocols. This study topographically analyses proliferation, apoptosis, and DNA ploidy.

Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi.

Atypical (dysplastic) melanocytic nevi are clinically heterogeneous malignant melanoma precursors, for which no topographic analysis of cell kinetic, cell cycle regulators and microsatellite profile is available. We selected low-grade atypical melanocytic nevi (92), high-grade atypical melanocytic nevi (41), melanocytic nevi (18 junctional, 25 compound) and malignant melanomas (16 radial growth phase and 27 vertical growth phase). TP53, CDKN2A, CDKN1A, and CDKN1B microsatellite patterns were topographically studied after microdissection; Ki-67, TP53, CDKN2A, CDKN1A, and CDKN1B expressions and DNA fragmentation by in situ end labeling for apoptosis were topographically scored. Results were statistically analyzed. A decreasing junctional–dermal marker expression gradient was observed, directly correlating with atypical melanocytic nevus grading. High-grade atypical melanocytic nevi revealed coexistent TP53–CDKN2A–CDKN1B microsatellite abnormalities, and significantly higher junctional Ki67–TP53 expression (inversely correlated with CDKN1A–CDKN1B expression and in situ end labeling). Malignant melanomas showed coexistent microsatellite abnormalities (CDKN2A–CDKN1B), no topographic gradient, and significantly decreased expression. Melanocytic nevi and low-grade atypical melanocytic nevi revealed sporadic junctional CDKN2A microsatellite abnormalities and no significant topographic kinetic differences. High-grade atypical melanocytic nevi accumulate junctional TP53–CDKN1A–CDKN1B microsatellite abnormalities, being progression TP53-independent and better assessed in the dermis. Melanocytic nevi and low-grade atypical melanocytic nevi show low incidence of microsatellite abnormalities, and kinetic features that make progression unlikely.

The correlation of regression with the grade of dysplasia (atypia) in melanocytic naevi

Sir: The diagnosis of atypical melanocytic naevus (AMN) is controversial, which partly explains its variable incidence. The AMN consensus definition includes the presence of lymphocytic inflammation, which is known to induce signs such as colour changes, swelling and erythema, considered to be criteria of atypical moles. The inflammation seen in naevus regression seems to be reactive to unidentified melanocytic changes, but its relationship to AMN grading remains unknown. We studied 123 clinically atypical naevi from 65 female and 46 male subjects aged 36.56 ± 11.94 years. No significant differences were observed associated with regression regarding age and sex distribution, location, gross appearance, family or personal history of atypical mole syndrome ⁄ malignant melanoma. Cases showing evidence of scarring, incomplete resection or features suggesting congenital onset were excluded. Multiple haematoxylin and eosin-stained sections of the whole lesion were evaluated by two independent observers (A.B. and S.J.D-C.). In cases of disagreement, grading was assigned during simultaneous inspection. Reproducibility data were not recorded. AMN were required to show both architectural and cytological atypia, including lentiginous melanocytic hyperplasia (discontinuous ⁄ confluent), suprabasilar melanocytes (little ⁄ fully pagetoid spread), nesting variation and

Trichilemmal carcinoma with neuroendocrine differentiation.

We report a 12‐mm nodular, cream‐coloured skin lesion that appeared on the left nasal ala in an 81‐year‐old man. This trabecular infiltrative tumour showed keratin microcysts, stromal hyalization, cytoarchitectural malignancy features, colonizing melanocytes, and immunoexpression of epithelial membrane antigen, cytokeratin 15/20, chromogranin, synaptophysin and CD56. To our knowledge, this is the first documented case of a trichilemmal carcinoma with neuroendocrine differentiation and melanocyte colonization, which is suggested by the trabecular growth pattern and requires immunohistochemical confirmation. The colonization of the epithelial nests by nonatypical dendritic or spindle melanocytes is a clue to morphological recognition of pilar neoplasms, along with the presence of stromal induction (CD34‐positive peritumoral spindle cells), catagen‐like apoptotic bodies, calcifications, keratin microcysts and cell balls.

Dermoscopy of Trichostasis Spinulosa

T RICHOSTASIS SPINULOSA (TS) IS A RELAtively common but underdiagnosed disorder of hair follicles that retain successive telogen hairs. It has been described within skin lesions (secondary TS) or as an isolated finding (primary TS). Dermoscopy may help identify the characteristic hair tuft. We report 2 cases of TS. The first case involved a 23-year-old woman who presented with a long-standing history of a light-brown papule on the lower part of her back. There was a black punctum in the upper central area of the lesion (Figure 1). Dermoscopy showed a sparse pigment network, multiple commalike blood vessels that are typical of intradermal melanocytic nevi, a few peripheral vellous hairs, and a small hair tuft emerging from the central punctum (Figure 2). Histologic examination confirmed the presence of an intradermal melanocytic nevus along with dilated folliculosebaceous units containing several cross-sectioned hair shafts (Figure 3). The second case involved a 30-yearold man who presented with a micropapular eruption on both flanks. Dermoscopy showed multiple vellous hairs erupting through the follicles (Figure 4). Hair tufts are the result of folliculosebaceous hamartomas with multiple units around a central pore (trichofolliculomas) or retained hair shafts within follicles with infundibular keratosis (TS). Trichostasis spinulosa may appear as an isolated finding or in association with expansile nondestructive lesions that narrow hair infundibulae, such as melanocytic nevi, seborrheic keratoses, syringomas, or nodular basal cell carcinomas. Dermoscopy is helpful in diagnosing TS.