Zsolt B. Argenyi

Atypical Spitz nevi/tumors : Lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome

The biological nature of Spitz nevi/tumors and their diagnostic distinction from, or relationship to, melanoma remain unresolved issues. In this report, a series of 30 melanocytic lesions removed from 28 patients, including atypical Spitz nevi/tumors and metastasizing Spitzoid tumors/melanomas, were evaluated by a panel of dermatopathologists to evaluate interobserver diagnostic concordance and to assess the prognostic power of histological criteria. For inclusion in the study, each lesion had to display some criteria for the Spitz nevus, and in addition one of the following was required: (1) definitive clinical outcome such as metastasis or death of disease, or (2) long-term follow-up if the patient remained disease free. Each lesion was reviewed independently and blinded as to the clinical data by 10 pathologists, who categorized them as (1) typical Spitz nevus/tumor, (2) atypical Spitz nevus/tumor, (3) melanoma, (4) tumor with unknown biological potential, or (5) other melanocytic lesion. There was limited discussion of criteria before the review. Evaluation of 17 Spitzoid lesions yielded no clear consensus as to diagnosis; in only one case did six or more pathologists agree on a single category, regardless of clinical outcome. Notably, however, some lesions that proved fatal were categorized by most observers as either Spitz nevi or atypical Spitz tumors. Conversely, seven or more pathologists scored 13 lesions as melanoma. These results illustrate (1) substantial diagnostic difficulties posed by many Spitz tumors, especially those with atypical features, even among experts, and (2) the lack of objective criteria for their distinction from melanoma and for gauging their malignant potential. Nevertheless, our observations do suggest that a biological relationship exists between the Spitz nevus/tumor and melanoma.

Detection of Human Papillomavirus DNA in Cutaneous Squamous Cell Carcinoma among Immunocompetent Individuals

The presence of certain types of human papillomavirus (HPV) is a known risk factor for the development of anogenital squamous cell carcinomas (SCCs). A similar association has been hypothesized for cutaneous SCCs, although, to our knowledge, no studies to date have combined sensitive HPV DNA detection techniques with epidemiologic data controlling for known risk factors to explore the association. We designed a case-control study examining HPV prevalence using highly sensitive PCR-detection assays in tissue samples from 85 immunocompetent patients with histologically confirmed SCCs and 95 age-matched individuals without a prior history of skin cancer. A standardized interview was administered to all study subjects to collect information pertaining to potential confounding variables. The overall detection rate of HPV DNA was high in case lesions (54%) and perilesions (50%) and in both sun-exposed normal tissue (59%) and non-sun-exposed normal tissue (49%) from controls. In comparing case tissue to control tissue, there was no differential detection of HPV DNA across various HPV species. However, HPV DNA from beta-papillomavirus species 2 was more likely to be identified in tumors than in adjacent healthy tissue among cases (paired analysis, odds ratio=4.0, confidence interval=1.3-12.0). The high prevalence of HPV DNA detected among controls suggests that HPV DNA is widely distributed among the general population. However, the differential detection of HPV beta-papillomavirus species in tumors among cases suggests that certain HPV types may be involved in the progression of cutaneous SCCs.

A variant of lymphomatoid papulosis simulating primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. Description of 9 cases.

Lymphomatoid papulosis (LyP) is a recurrent, self-healing eruption belonging to the spectrum of cutaneous CD30+lymphoproliferative disorders. Three main histologic subtypes of LyP are recognized: type A (histiocytic), type B (mycosis fungoides—(MF)-like), and type C (anaplastic large cell lymphoma–like). We reviewed 26 biopsies from 9 patients (M:F=6:3, median age: 29; mean age 27,2; age range 10 to 38) who presented with clinical features typical of LyP but with histopathologic aspects that resembled primary cutaneous aggressive epidermotropic CD8+cytotoxic T-cell lymphoma. In all but 1 case atypical lymphoid cells showed expression of CD30, and in 8 of 9 cases a T-cell cytotoxic phenotype could be observed (βF1+, CD3+, CD4−, CD8+). Expression of at least 1 cytotoxic marker (TIA-1, granzyme B) was observed in all cases. Polymerase chain reaction analysis of the T-cell receptor genes revealed a monoclonal rearrangement in 2 of 5 cases tested. Follow-up data available for 8 patients (mean follow-up time: 84 mo, median: 32.5 mo; range: 1 to 303 mo) revealed that none of them developed systemic involvement or signs of other cutaneous lymphomas. This cytotoxic variant of LyP may be histopathologically indistinguishable from primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma, and may be the source of pitfalls in the diagnosis and classification. We propose the term LyP type D for this unusual variant of the disease. Accurate clinicopathologic correlation is required in this setting, with crucial implications regarding prognosis and management of patients.

Nerve sheath myxoma (neurothekeoma) of the skin: light microscopic and immunohistochemical reappraisal of the cellular variant*

Nerve sheath myxoma (NSM) is a rare cutaneous neoplasm, the histogenesis of which is controversial. Fifteen cases of NSM were studied by routine light microscopy and with a broad panel of immunohistochemical stains. NSM were classified into three groups based on cellularity, mucin content and growth pattern. 1) The hypocellular (myxoid) type (5/15 cases) showed frequent encapsulation or sharp circumscription. Immunohistochemically this type was strongly positive for S‐100 protein and collagen type IV and variably positive for epithelial membrane antigen. 2) The cellular type (4/15 cases) had scant mucin and ill‐defined nodular or infiltrating growth. Immunostaining showed positive reaction for neuron specific enolase (2/4), Leu‐7 (1/4) and smooth muscle specific actin (2/4), and was negative with the oilier antibodies. 3) The “mixed type” (6/15 cases) had variable cellularity and mucin content with poor demarcation and variable immunolabeling. We conclude that: 1) there are major light microscopic and immunohistochemical differences between the classical hypocellular (myxoid) and the cellular forms of NSM (neurothekeoma); 2) while the immunohistochemical results support the presence of nerve sheath differentiation in the classical forms of NSM, and to some extent in the mixed forms, there is an absence of convincing evidence of neural differentiation in the cellular variant by either light microscopy or immunohistochemistry; 3) the variable immunophenotypes suggest that differentiation other than neural may take place in CNT.

Minocycline-related cutaneous hyperpigmentation as demonstrated by light microscopy, electron microscopy and X-ray energy spectroscopy

Argenyi ZB, Finelli L, Bergfeld WF, Tuthill RJ, McMahon JT, Ratz JL, Pefroff N. Minocycline‐related cutaneous hyper‐pigmentation as demonstrated by light microscopy, electron microscopy and X‐ray energy spectroscopy.

Acute neutrophilic dermatosis with myeloblastic infiltrate in a leukemia patient receiving all-trans-retinoic acid therapy.

We report a case of leukemia-associated acute febrile neutrophilic dermatosis (Sweets syndrome) that is unique because its initial histologic findings mimicked leukemia cutis. Otherwise, the clinical manifestations and response to corticosteroid therapy were typical of Sweets syndrome. The onset of the dermatosis coincided with the onset of neutrophilic differentiation induced by single-agent leukemia therapy with all-trans-retinoic acid (ATRA). Subsequent exacerbation of the manifestations of Sweets syndrome and the ultimate conversion of the histologic picture to the expected mature neutrophilic dermal infiltrate coincided with the completion of neutrophilic differentiation in the peripheral blood and bone marrow. The ability of immature neutrophil precursors to induce cutaneous lesions of Sweets syndrome may indicate an ATRA-induced functional maturation that slightly precedes its effect on morphologic maturation. We conclude that a cutaneous infiltrate of early neutrophil precursors does not preclude a diagnosis of Sweets syndrome in patients with acute leukemia who respond to ATRA therapy.

Dysplastic naevi with moderate to severe histological dysplasia : a risk factor for melanoma

Background  The risk of malignant melanoma associated with histologically dysplastic naevi (HDN) has not been defined. While clinically atypical naevi appear to confer an independent risk of melanoma, no study has evaluated the extent to which HDN are predictive of melanoma.

Human parvovirus B19-induced vesiculopustular skin eruption

Erythema infectiosum, fifth disease, is a usually benign macular or maculopapular exanthem of childhood caused by the human parvovirus B19. A 27-year-old woman with a serologically documented human parvovirus infection who presented with a hemorrhagic exanthem and enanthem with areas of pustules and pseudo-pustules is described. The histologic findings were unusual because they combined the histologic features of morbilliform and vesiculopustular viral lesions. This case serves to underscore the occurrence of human parvovirus infection in adults. Further, it demonstrates the need to include parvovirus infection in the differential diagnosis of virally induced vesiculopustular skin eruptions.

Ultrastructural spectrum of cutaneous nerve sheath myxoma/cellular neurothekeoma

The histogenesis of cutaneous nerve sheath myxoma (NSM)/ cellular neurothekeoma (CNT) is still controversial. In this study, we examined the ultrastructural features of 16 NSM (3 classical, 11 CNT, and 2 mixed NSM/CNT). We classified the cells into 4 groups ultrastructurally. Type 1 cells were un‐differentiated polygonal cells with ovoid nuclei, cytoplasmic microfilaments, and occasionally with microfilament‐associated dense bodies. In most cells, the cytoplasmic membrane showed focal membranous densities and occasional basal‐lamina‐like material. This cell type comprised approximately 90% of CNT. Type II cells were more differentiated, had ovoid or spindled shapes, were rich in intracytoplasmic filaments, and were surrounded by continous basal lamina. These cells were consistent with Schwann cells and were present in the classical and mixed forms of NSM, and in a single case of CNT. Type III cells had features of perineurial cells and were relatively rare in classical NSM. Type IV cells resembled fibroblasts and were encountered in all variants of NSM. These results support the‐view that 1) the classical NSM has neural (mainly Schwann cell) differentiation, 2) CNT is predominantly composed of undifferentiated cells with partial features of Schwann cells, smooth muscle cells, myofibroblasts and fibroblasts, suggesting a divergent differentiation, and 3) CNT and NSM represent a histologic spectrum, but in CNT, the neural features are not fully expressed.

Cutaneous angiomyolipoma : a light-microscopic, immunohistochemical, and electron-microscopic study

We report a case of cutaneous angiomyolipoma found on the helix of a 67-year-old man. The lesion was studied by routine light microscopy, special stains, immunohistochemical methods, and electron microscopy. Histologic examination showed a well-circumscribed nodule in the dermis composed of an intimate mixture of blood vessels, smooth muscle, and mature fat. These components were confirmed by special stains, immunohistochemistry, and electron microscopy. We concluded that the unique features of this lesion distinguish it from other lesions such as angiomyoma, angiolipoma, and other mixed mesenchymal tumors. This report demonstrates that the features considered diagnostic of angiomyolipoma can occur in extrarenal sites and, therefore, this diagnosis cannot be excluded on the basis of site alone.