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Background Benign melanocytic rests are a frequent finding in superficial lymph nodes removed during sentinel lymph node biopsies for melanoma. Whereas the histopathology of these deposits is well understood, very little is known regarding melanocytic lymph node deposits in the setting of giant congenital melanocytic nevi. Methods We analyzed lymph nodes removed from the drainage basin of giant congenital melanocytic nevi in three patients who had developed melanoma within their giant congenital nevi. Results Two of three patients showed widespread, capsular and parenchymal melanocytic deposits in multiple nodes (9 of 11 nodes in one patient and 6 of 8 in the other). Melanocytes were small, non-mitotically active and resembled those in the associated giant congenital melanocytic nevus. Melanocytes were arranged singly and in small nests ∼0.05 mm in diameter, with some larger sheets up to 1 mm. Nodal melanocytes stained for Melan A and S100 on immunohistochemical evaluation, but showed negative or minimal HMB-45 reactivity. Conclusions Evaluation of lymph nodes in the setting of giant congenital melanocytic nevi is complicated by the presence of often numerous, parenchymal melanocytic nevic deposits. Bland cytology and minimal or absent HMB-45 staining may be helpful in differentiating these nodal melanocytic nevi from metastatic melanoma. We term this phenomena large congenital nodal nevus.

Background Histopathologic examination is sometimes inadequate for accurate and reproducible diagnosis of certain melanocytic neoplasms. As a result, more sophisticated and objective methods have been sought. The goal of this study was to identify a gene expression signature that reliably differentiated benign and malignant melanocytic lesions and evaluate its potential clinical applicability. Herein, we describe the development of a gene expression signature and its clinical validation using multiple independent cohorts of melanocytic lesions representing a broad spectrum of histopathologic subtypes. Methods Using quantitative reverse-transcription polymerase chain reaction (PCR) on a selected set of 23 differentially expressed genes, and by applying a threshold value and weighting algorithm, we developed a gene expression signature that produced a score that differentiated benign nevi from malignant melanomas. Results The gene expression signature classified melanocytic lesions as benign or malignant with a sensitivity of 89% and a specificity of 93% in a training cohort of 464 samples. The signature was validated in an independent clinical cohort of 437 samples, with a sensitivity of 90% and specificity of 91%. Conclusions The performance, objectivity, reliability and minimal tissue requirements of this test suggest that it could have clinical application as an adjunct to histopathology in the diagnosis of melanocytic neoplasms.

The diagnosis of scabies infestation is straightforward in cases where mite parts are largely visible; however, mites are often not captured in a specimen's planes of section. Polariscopic examination is a fast and simple adjunctive diagnostic tool to light microscopy. We describe the unique polariscopic findings in scabies infestation. Two cases of crusted scabies and eight cases of typical scabies were subjected to polariscopic examination. Diagnostic mite parts were visualized in at least one section in all cases. Attached and detached spines as well as scybala (fecal material) are polarizable. Specifically, spines show a polarizable outer sheath with dark central core while scybala show peripherally concentrated, stippled birefringence. Similar stippled birefringence is visible within the gut of some mites whereas significant birefringence is not appreciated in other mite parts. These results suggest that polariscopic examination is a helpful clue in the diagnosis of scabies infestation, especially in cases where the body of the mite is not visualized.

Nevus sebaceus (NS) is a congenital skin hamartoma that presents in childhood. Tumors may arise within these lesions over time. Mutations in the PTCH gene have been associated with both NS and some of the developing tumors. Only nine documented cases of basal cell carcinoma arising in nevus sebaceus in childhood are available. We present a case of an 8-year-old male with nevus sebaceus who developed a basal cell carcinoma. Evaluation for constitutional PTCH gene mutation and loss of heterozygosity (LOH) from the BCC within the NS did not reveal an underlying mutation. We further discuss the literature regarding prophylactic excision of NS.

Background: Bullous pemphigoid (BP) is characterized clinically by the onset of pruritic urticarial plaques, vesicles and bullae in a predominantly elderly population. While the diagnosis may be suspected on routine hematoxylin and eosin histology of formalin-fixed paraffin-embedded tissue, fresh-frozen tissue must be used to show the immunologic nature of the bullous process by direct immunofluorescence (DIF). The diagnosis is further confirmed and separated from epidermolysis bullosa acquisita (EBA) by subsequent serologic studies to detect antibodies directed against BP180 and BP230 antigens and characteristic antibody deposition on salt-split skin. Methods: Using a polyclonal complement fragment 4d (C4d) antibody, we stained formalin-fixed paraffin-embedded skin biopsy specimens from cases of BP and controls. Results: We showed characteristic linear basement membrane deposition of C4d in formalin-fixed paraffin-embedded tissue in seven of nine cases diagnosed as BP vs. EBA by DIF on fresh-frozen tissue. None of the four controls for which we had adequate tissue were positive. Conclusion: These results indicate that formalin-fixed paraffin-embedded tissue can be stained for the immunoreactant C4d to show characteristic immunoreactant deposition, potentially obviating the need for repeat biopsy for DIF and allowing clinicians to proceed to serologic confirmation of BP.

Transgenic mice expressing hepatocyte growth factor (HGF) develop cutaneous melanocytic tumors following neonatal UV exposure. On the albino FVB background, tumors arise from the epidermal-dermal junction and exhibit radial growth phase pattern reminiscent of human melanoma. Here, we examined the histologic spectrum of UV-induced melanocytic tumors in HGF mice on a pigmented (C57BL/6 x C3H/HeN)F1 background. Neonatally-irradiated (4000 J/m2) mice were monitored for 43 weeks, and 31/34 (91%) animals developed a total of 163 melanocytic tumors. Of 54 primary tumors analyzed, most (49/54, 91%) demonstrated exclusively dermal collections of epithelioid cells with voluminous densely pigmented cytoplasm. Seven of these also demonstrated a population of spindled cells with mitoses. Several (3/54, 6%) tumors exhibited a junctional component with melanocytes present in the epidermis. Staining with PEP8 confirmed the presence of interfollicular melanocytes at the epidermal junction in neonatal skin. Thus in contrast to HGF animals on the FVB background, HGF animals on the pigmented (C57BL/6 x C3H/HeN)F1 background do not develop classic radial growth phase melanoma but rather predominantly develop dermal melanocytomas resembling the epithelioid blue nevi and pigmented epithelioid melanocytomas occasionally seen in humans. These results demonstrate the influence of genetic background on histologic pattern of UV-induced melanomas in mice.

Background: Distinguishing merkel cell carcinoma (MCC), small cell lung carcinoma (SCLC) metastatic to the skin, and atypical basal cell carcinoma (BCC) can be problematic in some cases. Significant differences in the biology of these tumors necessitate that they need to be distinguished from one another. Methods: We evaluated the immunophenotypic characteristics of 22 MCCs, nine SCLCs, and 19 BCCs using antibodies to cytokeratin 20 (CK20), thyroid transcription factor-1 (TTF-1), CD117, and DNA topoisomerase II-α (topo II). Results: Nineteen of 22 MCCs stained with the antibody to CK20, none stained with anti-TTF-1, and 13 stained with anti-CD117. No SCLC stained with anti-CK20, all stained with anti-TTF-1, and eight stained with anti-CD117. No BCC stained with any of the three markers. The proliferative index (PI), determined by the expression of topo II, was similar for SLCLs (mean 58.5 ± 9.0%) and MCCs (mean 45.2 ± 12.4%) and was lowest in BCCs (mean 25.0 ± 8.7%). Conclusions: CK20 and TTF-1 appear to be reliable in distinguishing MCC from SCLC. CD117 is expressed in both MCC and SCLC, limiting its diagnostic utility. CK20, TTF-1, and CD117 are not expressed in BCC. The high PI seen in MCCs suggests a role for topoisomerase II inhibitors in their treatment.

Significant advances in identification of etiologies of inherited thrombosis have been recently reported. A point mutation in coagulation factor V (factor V Leiden) results in resistance to activated protein C and probably represents the most common genetic risk factor for venous thrombosis. A metabolic disorder, homocysteinemia, is now known to be an important risk factor for both arterial and venous thrombosis. Many patients with recurrent thrombosis will have more than one genetic risk factor identified. Recognition of these new disorders should permit a diagnosis to be achieved in at least half of patients evaluated for inherited thrombosis.

Aprosencephaly is a rare, lethal malformation sequence of the central nervous system that has been attributed to a postneuralation encephaloclastic process. We describe autopsy findings consistent with aprosencephaly in 2 fetuses conceived from a consanguineous mating (first cousins). Both showed anencephalic manifestations; however, the crania were intact, with fused sutures. The neuropathologic findings were essentially identical. Each fetus had complete absence of the telecephalon and pyramidal tracts, rudimentary diencephalic and mesencephalic structures, primitive cerebellar hemispheres, posterolateral clusters of primitive neural cells in the medullas suggesting an abnormality of neural migration, a normally-formed spinal cord, and retinal dysplasia within normally-formed globes. In addition, both fetuses manifested a peculiar perivascular mesenchymal proliferation seen only within the central nervous system. The similarity of these cases, coupled with parental consanguinity, suggests a primary malformation in brain development due to the homozygous representation of a mutant allele. We hypothesize that these patients may represent a defect in a gene important in brain development, the nature of which has yet to be elucidated.

A 25-year-old Micronesian man from the island of Otia developed erythematous plaques on his legs. He was diagnosed with erythema nodosum and treated with systemic prednisone. Two months later, he presented with erythematous nodules on his forehead, cheeks, and chin (Fig. 1). Examination revealed scattered violaceous papules on his chest, arms, forearms, hands, and feet, and deep purple macules on his palms and soles. Laboratory evaluation included negative serologies for human immunodeficiency virus, rapid plasma reagin, and hepatitis A, B, and C. Figure 1. Erythematous papules and nodules cover the forehead, nose, cheeks, chin, and ears Download figure to PowerPoint Routine histopathology revealed nodular aggregates of histiocytes, plasma cells, and lymphocytes. Histiocytes showed basophilic clusters of organisms within vacuoles, suggesting globi. Acid-fast stain revealed numerous acid-fast-positive rod-shaped organisms. The bacterial index on the Fite stain was four (bacterial index/Ridley's logarithmic scale, indicating 10–100 bacteria/high power field) (Fig. 2). An acid-fast stain obtained from a smear of tissue was positive for acid-fast bacilli, but no acid-fast bacilli were cultured. Figure 2. The bacterial index on the Fite stain was four Download figure to PowerPoint After the first day of treatment with dapsone 100 mg, rifampin 600 mg, and clofazimine 50 mg, the patient complained of burning and pain in his ankles and wrists. There was intense erythema within the lesions. Edema developed in his hands and feet. Consultation with the Gillis W. Long Hansen's Disease Center in Carville, Louisiana, recommended prompt treatment with corticosteroids. The edema of the hands and wrists was treated as a type I reversal reaction with prednisone 1 mg/kg/day. Subsequently, the edema and neuralgia quickly resolved in his distal extremities.