Klaus J. Busam

Dermoscopic Findings in Cutaneous Metastases

IMPORTANCEnCutaneous metastases rarely develop in patients with cancer but have important implications for prognosis and treatment. While dermoscopy is useful for many skin lesions, few data exist regarding dermoscopic findings in cutaneous metastases.nnnOBSERVATIONSnWe reviewed high-quality dermoscopic images of 20 outpatients with biopsy-proven cutaneous metastases and known diagnosis of underlying visceral malignancy and correlated these findings with clinical and histologic data. Most lesions were pink or flesh-colored, but 3 of 20 were pigmented. All 17 nonpigmented lesions demonstrated a vascular pattern on dermoscopy, with 15 of 17 (88%) having discrete vessels and 2 of 17 (12%) showing pink homogeneous structureless areas. Serpentine, or linear irregular, vessels were most common. In the 3 pigmented lesions (all metastatic breast carcinoma), various melanocytic patterns were observed.nnnCONCLUSIONS AND RELEVANCEnDermoscopically visible vascular structures within a cutaneous nodule in patients with a known cancer diagnosis should raise suspicion for cutaneous metastasis. Pigmentation in such lesions, in the absence of a history of melanoma, suggests a primary breast carcinoma. The high prevalence of vascular structures among cutaneous metastases may suggest a role for angiogenesis in their pathogenesis. These findings support the use of dermoscopy in the evaluation of suspected skin metastases or in the assessment of lesions of unknown origin in patients with cancer.

Porokeratosis of Mibelli following bone marrow transplantation

Backgroundu2002 Porokeratosis is a rare disorder of keratinization with both autosomal dominant and acquired forms. Immunosuppression has been associated with the development of porokeratosis in numerous case reports and series. To our knowledge, however, only five cases of porokeratosis have been reported following bone marrow transplantation.

Cutaneous Hemophagocytosis After Alemtuzumab Injection in a Patient With Sézary Syndrome

Approximately 20% of patients present with atypical or variant forms of PR, which are less readily recognized than typical eruptions and may pose a diagnostic challenge.2,3 The morphologic characteristics of the eruption may be papular, vesicular, purpuric or hemorrhagic, or urticarial. Very small lesions will be observed in papular PR, and PR with enormous plaques is known as pityriasis rosea gigantea of Darier. A morphologic variant characterized by atypical large patches that tend to be few in number and coalescent has been described. In this variant, commonly referred to as pityriasis circinata et marginata of Vidal or limb-girdle PR, the eruption generally appears in the axillae, the groin, or both, with the trunk and extremities usually spared.4,5 A simple classification for atypical pityriasis rosea has been proposed by Chuh and Zawar (Box).6 In our patient, the eruption fulfills all 3 essential clinical features (discrete annular lesions, scaling, and peripheral collarette scaling with central clearance on at least 2 lesions), all 3 optional clinical features (relative truncal distribution, orientation along skin cleavage lines, and herald patch), and none of the exclusional clinical features. This case has clinical features of localized PR, papular PR, and pityriasis circinata et marginata of Vidal. It should also be noted that the involvement of penile and scrotal skin is rarely reported in PR. Physicians should be aware of the wide spectrum of PR variants so that appropriate management and reassurance can be offered.

The Spitz Nevus and Variants

The spitzoid melanocytic neoplasms constitute a distinctive and at the same time enigmatic group of melanocytic lesions which are defined by a characteristic histology and developmental origin. The histological attributes which set these lesions apart from other melanocytic neoplasms are prototypic large epithelioid and/or spindled melanocytes usually arranged in a distinctive architectural configuration. Because of these histological characteristics, these lesions are frequently misdiagnosed as conventional melanoma.

BRAF, NRAS, and GNAQ Mutations in Conjunctival Melanocytic Nevi

Purpose To evaluate BRAF, NRAS, and GNAQ mutations in surgical specimens of common and blue conjunctival melanocytic nevi. Methods Surgical specimens from 25 conjunctival melanocytic nevi (23 common and 2 blue) of 25 patients were evaluated. All common nevi were analyzed immunohistochemically for the expression of BRAF V600E or NRAS Q61R. One lesion with negative immunoreactivity and for all blue nevi, a hybridization capture-based next-generation sequencing method was employed for mutation analysis. For common nevi, genetic features were compared with clinical and histopathologic findings. Continuous variables (age at excision and largest basal diameter) were compared with a Studentss t-test and all categoric variables were compared with Fishers Exact Test. Results Of common melanocytic nevi, 9 (39.1%) were immunoreactive for NRASQ61R and 13 (56.5%) were immunoreactive for BRAFV600E. One common nevus, which was immunonegative for both BRAFV600E and NRASQ61R was found to harbor an NRASQ61K mutation by sequence analysis. Patients with NRAS-mutated nevi were more likely to report occurrence of the lesion prior to 18-years old and more likely to have intrinsic cysts. The mean largest basal diameter was 6.0 and 3.5 mm for NRAS- and BRAF-immunoreactive lesions, respectively (P = 0.003). GNAQ mutations were identified in each of the two blue nevi of this study. Conclusions These findings document that common conjunctival melanocytic nevi have mutually exclusive mutations in BRAF and NRAS. The two conjunctival blue nevi harbored GNAQ mutations. This suggests the driver mutations of conjunctival nevi are similar to those of nevi of the skin. At the molecular level, conjunctival nevi appear more like cutaneous nevi than choroidal nevi.

Dermal Melanocytoses, Blue Nevi, and Variants

The subject of this chapter includes blue nevi and related proliferations of melanocytes, usually dendritic or spindled, primarily involving the reticular dermis. The nomenclature for this group of lesions is in part related to their clinical description (“blue nevus”) and/or distinct histopathological characteristics (“cellular” blue nevus). They share a mutation profile: mutations involving GNA11/GNAQ are common in this group of lesions [1, 2].

Biopsies, Tissue Processing, Immunohistochemistry, and Ancillary Techniques

The specimen submitted for histopathologic examination needs to provide critical diagnostic and prognostic information, such as symmetry and lateral and deep extension. Therefore, the proper procedure for most pigmented cutaneous lesions is an excisional biopsy. The biopsy should not be too large to avoid unnecessary removal of normal skin, if the lesion is benign, in which case, the biopsy constitutes definitive treatment. Furthermore one must consider if a sentinel lymph node biopsy will be performed, since a large excision usually disrupts lymphatic drainage and may affect the sentinel lymph node mapping and biopsy, if carried out before sentinel lymph node (SLN) biopsy. When the lesion is malignant, excision of the whole lesion becomes necessary, with margins appropriate for tumor thickness.

Melanocytic Proliferations of the Eye

Similar to the skin, there is a spectrum of benign congenital and acquired melanotic and melanocytic lesions of the conjunctiva. This includes congenital and acquired melanosis, melanocytic nevi, and melanomas.

Melanocytic Neoplasms of the Mucosa

Mucosal melanomas (MMs) are rare, accounting for only 1–2 % of all melanomas [1, 2]. The age-adjusted incidence rate of MM in the period 1996–2000 was 2.2 per million in the USA (compared to 161.7 per million for cutaneous melanoma) [2]. In contrast to the rising incidence of cutaneous melanoma, the incidence of MM has remained relatively stable.