The histologic spectrum of mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma). A review of 222 biopsies, including newly described patterns and the earliest pathologic changes.

We studied 222 skin biopsies of mycosis fungoides and Sézary syndrome (cutaneous T-cell lymphoma [CTCL]) to document the huge histologic spectrum and to evaluate the earliest histologic changes. Our results indicate that CTCL produces practically all of the patterns used for diagnosing inflammatory skin disease: superficial or superficial and deep perivascular without epidermal changes; spongiotic; psoriasiform, with or without a lichenoid infiltrate; interface, including lichenoid without vacuolar alteration, lichenoid with vacuolar alteration, and vacuolar alteration without a lichenoid infiltrate; follicular, with or without mucin; nodular and diffuse; vasculitis; vesicular; and panniculitis. Unusual examples resembling granuloma annulare, gyrate erythema, lichen planus, and pityriasis lichenoides were seen. To further document the spectrum within each pattern, we analyzed many variables, such as lymphocytic atypia, epidermotropism, epidermal contour, and composition of the dermal infiltrate. Common clues to the diagnosis of CTCL include epitheliotropism with little spongiosis; lymphocytes lined up along the basal layer; hyperconvoluted lymphocytes; and broad areas of slight hyperorthokeratosis that is compact or laminated, with subtle interspersed parakeratosis. Less common clues include Pautrier's microabscesses; granulomatous foci; coexistence of plasma cells and eosinophils; and rounded, hyperplastic rete ridges adjacent to flattened rete. The earliest changes of CTCL appear to be a sparse, superficial perivascular infiltrate with slight or no epidermal hyperplasia and with rare lymphocytes in the lower epidermis, especially the basal layer, often with hyperconvoluted nuclei. Our findings support the hypothesis that CTCL develops sui generis, rather than from another chronic dermatosis.

Pagetoid intraepidermal spread in Merkel cell (primary neuroendocrine) carcinoma of the skin.

Pagetoid intraepidermal spread of neoplastic cells was noted in six cases of Merkel (primary neuroendocrine) cell carcinoma of the skin. In two cases, the volume of the intraepidermal portion of the neoplasm was either equal to or more extensive than the dermal component. The intraepidermal component in all six cases was remarkable because of the following findings: the presence of cells with scant cytoplasm arranged both individually and as nests, sometimes along the dermoepidermal junction; splaying of the apical portions of basal keratinocytes by solitary neoplastic cells; incomplete rims of compressed basal keratinocytes at the peripheries of some junctional nests; and occasional contiguity of neuroendocrine carcinoma cells with those of Bowen's disease or solar keratosis. These features can be used to distinguish these Merkel cell carcinomas from other lesions that have a pagetoid pattern, even in superficial biopsies, and immunohistochemistry can confirm the diagnosis or resolve problematic cases. The occurrence of cutaneous neuroendocrine carcinoma situated largely in the epidermis raises the possibility that some of these tumors may arise from intraepidermal Merkel cells.

Clonal chromosomal abnormalities in cutaneous T-cell lymphoma.

Chromosome analysis from stimulated and unstimulated lymphocytes of blood, skin, and lymph nodes demonstrated a clonal chromosomal abnormality in eight of 46 patients with cutaneous T-cell lymphoma (CTCL). Nonclonal abnormalities were found in nine other patients. Unstimulated lymph node cultures identified the highest proportion of clonal changes. Clonal changes were found most often in patients with advanced disease, and in patients who tested positive with a monoclonal antibody previously shown to detect the T-cells involved in CTCL. Analysis of the eight abnormal clones and seven others found before or since this consecutive series showed that identifiable changes involving the known sites of T-cell receptor genes on chromosomes #7 and #14 were not usually present. An association between CTCL and chromosome rearrangements of chromosome #10 is suggested both from our cases and those found in the literature. This observation is of interest because this chromosome contains the gene for the interleukin-2 receptor.

Perifollicular hypopigmentation. A cause of variegate pigmentation and irregular border in melanocytic nevi.

BACKGROUND AND DESIGN: Clinical and histologic features of perifollicular hypopigmentation within melanocytic nevi are described. RESULTS: Perifollicular hypopigmentation was observed in congenital and acquired melanocytic nevi. When the area of hypopigmentation was found within the nevus, it was circular. When the hypopigmentation was located at the edge of the nevus, however, it formed a half circle that resulted in a notch in the outline of the lesion. The phenomenon occurred in nevi with terminal hairs as well as nevi with vellus hairs. In biopsy specimens from 15 melanocytic nevi, one or more of the following findings were observed around hair follicles when compared with the remainder of the nevus: decrease in the number of junctional melanocytes as nests and solitary units (n = 12), decrease in pigment within keratinocytes (n = 14), decrease in the number of melanocytes in the papillary dermis (n = 6), and decrease in the number of melanophages (n = 6). CONCLUSIONS: Perifollicular hypopigmentation is a cause of variegate pigmentation and irregular border in melanocytic nevi.

Unilateral pruritus after a stroke.

A patient with unilateral pruritus after a stroke is described. The neural pathways of pruritus and the role of the central nervous system in the initiation and modulation of the itch sensation are discussed. Pathways between the cerebral cortex and the medulla may play important roles in the sensation of pruritus.

Familial multiple desmoplastic trichoepitheliomas.

A kindred with familial multiple desmoplastic trichoepitheliomas is described. Desmoplastic trichoepitheliomas should be added to the group of lesions that indicate an inherited pattern when they occur as multiple primary tumors. The implications for nosologic status and treatment of desmoplastic trichoepitheliomas are considered.

The significance of eccentric foci of hyperpigmentation ('small dark dots') within melanocytic nevi. Analysis of 59 cases.

BACKGROUND AND DESIGN: Fifty-nine melanocytic nevi with eccentric foci of hyperpigmentation ("small dark dots") that measured primarily 1 to 2 mm in diameter were prospectively examined to determine the histologic correlates of the dark dots. RESULTS: Forty-one (69%) of the dark dots were due to increased melanin in epidermal melanocytes and/or keratinocytes, usually accompanied by melanophages; of these 41, six (15%) were associated with slight or moderate melanocytic nuclear atypia. Fifteen (25%) of the dark dots were due to increased dermal pigment that was either superficial or deep. Three (5%) of the dark dots were due to melanoma arising within a nevus. CONCLUSIONS: A small percentage of "small dark dots" within melanocytic nevi are due to melanoma. Biopsy specimens of nevi with small dark dots should be sectioned to ensure histologic examination of this focus of hyperpigmentation.

Periodic acid-Schiff-positive organisms in primary cutaneous Bacillus cereus infection. Case report and an investigation of the periodic acid-Schiff staining properties of bacteria.

Primary cutaneous Bacillus cereus infection frequently presents as a single necrotic bulla on the extremity of an immunocompromised patient. In lesional biopsy specimens and smears, the large gram-positive rods of B cereus may be mistaken for Clostridium species. This is a potentially serious error, as Bacillus species are resistant to penicillin and other beta-lactam antibiotics. We studied a case in which large periodic acid-Schiff-staining organisms were seen in the biopsy specimen from a necrotic bulla on the finger of a neutropenic patient with diffuse large cell lymphoma. The tissue biopsy specimen subsequently yielded a pure culture of B cereus. Staining with periodic acid-Schiff was then performed on a series of bacterial species in human tissue and from smears of culture colonies. The following bacterial species were found to be consistently periodic acid-Schiff positive after diastase digestion: B cereus, Corynebacterium diphtheriae, Propionibacterium acnes, Klebsiella pneumoniae, and Micrococcus luteus.

Cutaneous T-cell lymphoma. Refinement in the application of controversial histologic criteria.

The term cutaneous T-cell lymphoma was originally coined to encompass the spectrum of mycosis fungoides and Sézary syndrome. It has become increasingly evident that the histopathologic diagnosis of CTCL can be exceedingly challenging. A series of recent studies, however, have helped clarify the nature of the histologic findings in CTCL. Recently reported histologic data on mycosis fungoides, Sézary syndrome, and their variants is emphasized in this article, with special focus given to the findings in early lesions. A brief summary of lymphocyte immunophenotyping and the role of T-cell reception gene rearrangements in CTCL is included.

Making sense of the dysplastic nevus controversy. A unifying perspective.

There is currently much confusion regarding the "dysplastic nevus." There is justification for this confusion, given the abundance of seemingly contradictory statements in the literature. This article proposes a unifying perspective that can help reconcile seemingly contradictory statements and decrease confusion regarding the "dysplastic nevus." The proposed unifying perspective suggests that the "dysplastic nevus" does not exist in nature as a distinct clinical-pathologic entity, but that there is probably legitimacy to the concept of a "dysplastic nevus."

Disseminated Nocardia asteroides with pustules.

A case of disseminated Nocardia asteroides in a renal transplant recipient with cavitary lung lesions and cutaneous pustules is presented. Disseminated nocardiosis is a rare disease that occurs chiefly in the immunocompromised host and usually begins as a pleuropulmonary infection. Disseminated nocardiosis should be included in the differential diagnosis of pustules in immunosuppressed patients.

Histologic findings in acute HIV exanthem.

We describe a patient with acute HIV exanthem with papulovesicular lesions and epidermal necrosis. We also review the literature regarding the histopathologic findings of acute HIV exanthem, which appears to be most commonly characterized by a perivascular lymphocytic infiltrate without epidermal change, but which may be associated with spongiosis, vacuolar alteration, or epidermal necrosis.

Healthy individuals and patients with systemic lupus erythematosus have unique, person-specific spectra of antibodies detectable on immunoblots.

Through the technique of immunoblotting, the spectrum and organ specificity of antibodies in healthy individuals and patients with systemic lupus erythematosus were examined. It was demonstrated that healthy individuals and patients with autoimmune disease have antibodies, some tissue specific and some not tissue specific, which are present in a pattern that is unique to each individual.

Multinucleate cell angiohistiocytoma: a distinct entity diagnosable by clinical and histologic features.

BACKGROUND: Multinucleate cell angiohistiocytoma is a newly described entity; examples from the United States have not yet been reported. OBJECTIVE: Our purpose was to analyze the clinical and histologic features of this entity and confirm or refute its existence. METHODS: Seven cases were analyzed clinically and by light microscopy. RESULTS: Multinucleate cell angiohistiocytoma typically occurs in middle-aged women and consists of multiple, grouped, red-brown to violaceous papules that are dome-shaped or flat-topped, roundish and smooth in outline, sharply circumscribed, and occasionally coalescent. Typical sites are the legs, thighs, and backs of hands and fingers. Microscopic features are an increased number of blood vessels (usually capillaries and venules) that are small, rounded, and not well grouped, together with multinucleated histiocyte-like cells with scalloped borders. CONCLUSION: Multinucleate cell angiohistiocytoma is a distinct entity that is diagnosable clinically and histopathologically.

Solitary syringoma. Report of five cases and clinicopathologic comparison with microcystic adnexal carcinoma of the skin.

Five cases of solitary syringoma (SS) were found by the authors in a search of adnexal neoplasms seen over an 18-year period. These tumors all occurred in adults as mobile, flesh-colored, circumscribed papules of the facial skin, measuring < or = 5 mm in greatest dimension. Each was cured by simple punch or shave biopsy excision. Comparison with nine histologically similar variants of microcystic adnexal carcinoma (MAC) showed that the latter lesions differed from SS in that they showed much deeper invasion, with regular involvement of the underlying subcutis and perineural or vascular-adventitial infiltration. Moreover, SS was wider than it was deep on microscopic examination, whereas the converse pertained to MAC. Knowledge of the typical clinicopathologic attributes of these two tumor types should prevent clinicians and pathologists from confusing them with each other.

Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers.

To identify the sites in the p53 tumor suppressor gene most susceptible to carcinogenic mutation by sunlight, the entire coding region of 27 basal cell carcinomas (BCCs) of the skin was sequenced. Fifty-six percent of tumors contained mutations, and these were UV-like: primarily CC-->TT or C-->T changes at dipyrimidine sites. Such mutations can alter more than half of the 393 amino acids in p53, but two-thirds occurred at nine sites at which mutations were seen more than once in BCC or in 27 previously studied squamous cell carcinomas of the skin. Seven of these mutation hotspots were specific to skin cancers. Internal-cancer hotspots not located at dipyrimidine sites were not mutated in skin cancers; moreover, UV photoproducts were absent at these nucleotides. The existence of hotspots altered the process of inactivating p53 in BCC compared to other cancers: allelic loss was rare, but 45% of the point mutations were accompanied by a second point mutation on the other allele. At least one of each pair was located at a hotspot. Sunlight, acting at mutation hotspots, appears to cause mutations so frequently that it is often responsible for two genetic events in BCC development.