Artur Zembowicz

Background:  The term lentiginous melanoma was recently used for atypical melanocytic proliferations sharing some histological features with lentigo maligna and associated with a protracted in situ stage before invasion. Lentiginous melanoma was characterized by predominantly single‐cell lentiginous growth pattern with focal junctional nests and pagetoid spread, preservation of the dermoepidermal junction, limited cytological atypia, and lack of significant solar elastosis. We report five similar cases.Methods:  Histological review of routine sections with clinicopathological correlation.Results:  Three patients were male and two were female. The age at presentation ranged from 24 to 66 years. All lesions arose on the truck or proximal extremities. All five cases fulfilled histological criteria proposed for lentiginous melanoma. None of the lesions showed significant solar elastosis. One lesion was followed clinically and histologically for 16 years without intervening treatment. It had three local recurrences before culminating in invasive melanoma.Conclusions:  Our observations support recent efforts to distinguish lentiginous melanoma as a distinct clinicopathological entity. Lentiginous melanoma can remain in situ for a long time before invasion and may be considered an analogue of lentigo maligna occurring on non‐severely sun‐damaged skin. Familiarity with the histological features of this variant is important for its early recognition and treatment.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is an underrecognized low-grade carcinoma with predilection to the eyelid. Only 4 cases of this entity have been described in the literature. Here, we describe 12 cases of EMPSGC. The lesions were twice as frequent in females than males with an average age of 70 years (range, 48-84 years). Clinically, they presented as a slowly growing cyst or swelling. The most common site of occurrence was the lower eyelid (8 cases). Two lesions occurred on the upper eyelid and 2 on the cheek. Histologically, they were well-circumscribed, typically multinodular tumors with solid or partially cystic nodules, frequently showing areas of papillary architecture. Focal cribriform arrangements were also present. The nodules were formed by uniform small- to medium-sized oval to polygonal epithelial cells with lightly eosinophilic to bluish cytoplasm. The nuclei were bland with diffusely stippled chromatin and inconspicuous nucleoli. Intracytoplasmic and extracellular mucin was usually present. Mitotic activity was present but never brisk. All tumors examined immunohistochemically expressed at least one neuroendocrine marker, synaptophysin or chromogranin. CD57 and neuron specific enolase, secondary markers of neuroendocrine differentiation, were expressed in most cases. All tumors tested expressed estrogen and progesterone receptors, cytokeratin 7, low molecular cytokeratin Cam5.2, and epithelial membrane antigen and were negative for cytokeratin 20 and S-100 protein. Calponin, smooth muscle actin, and p63 immunohistochemical stains did not disclose myoepithelial cells around larger tumor nests in most cases, supporting the notion that EMPSGC is an invasive carcinoma. In 10 cases, cystic areas lined by benign epithelium indistinguishable from eccrine ducts were present. In some foci, the benign ductal epithelium was undermined or replaced by carcinoma in situ with similar cytologic features to the solid or papillary areas of EMPSGC. Myoepithelial cells were preserved in the areas of in situ carcinoma. In 6 cases, EMPSGC was associated with invasive mucinous carcinoma. In situ carcinoma and mucinous carcinoma also expressed neuroendocrine markers. Clinical follow-up showed no recurrences or metastases, consistent with low-grade carcinoma. The series provides histologic evidence for a multistage progression of noninvasive sweat gland neuroendocrine carcinoma to EMPSGC and then to mucinous carcinoma of the eyelid. Although the data from this series support the notion that the prognosis of EMPSGC and mucinous carcinoma is good, longer follow-up is needed for better understanding of their pathogenesis and clinical behavior.

Dermal dendritic melanocytic proliferations are a broad group of congenital and acquired melanocytic lesions characterized by the presence of dermal spindled and dendritic cells resembling melanocytes migrating from the neural crest to the epidermis. Historically, they were subdivided into dermal melanocytoses (naevus of Ota, Ito, Mongolian spot and related conditions), blue naevi and malignant blue naevi. The purpose of this review is to provide an update on recent developments in the field with emphasis on new entities and their differential diagnosis.

The patient was a 77‐year‐old male former smoker, with history of several basal cell carcinomas (BCCs) in sun‐protected areas around the waistline, who presented with another small ulceration on the anterior right upper scrotum near the base of the penis. BCC was suspected clinically and the lesion was treated with cryosurgery. The tumor recurred, became raised, and began to bleed. On examination, it was found to be a 3 cm × 4 cm, raised, light and dark gray variegated lesion with fissures, crusted bloody scale, and necrosis. There were no other penile, testicular, or scrotal lesions or masses. There was no regional lymphadenopathy. An excisional biopsy was performed. It showed nodular BCC surrounded by a cellular proliferation of round histiocytic cells with convoluted, lobulated and reniform nuclei and abundant cytoplasm (Fig. 1). The histiocytic proliferation was associated with numerous eosinophils. Histological features and immunohistochemical phenotype, including expression of CD1a and S‐100 antigens by histiocytic cells, were all consistent with Langerhans cell histiocytosis. As expected, BCC expressed keratin. (a) Low magnification (×40) view of the scrotal tumor showing nodular basal cell carcinoma surrounded by a cellular zone of Langerhans cell proliferation. (b) Langerhans cells showed typical irregular reiniform nuclei with convoluted outlines and were associated with eosinophilic infiltrate (×400). In immunohistochemical studies, they expressed (c) S‐100 and (d) CD1A antigens (both ×400) image The patient had no history of exposure to ionizing radiation, chemotherapy, immunosuppressive medications, prior lymphoma or other malignancy. However, he spent 4 years on a ship loading coal into the furnace of a steam engine, during which he slept in adjacent quarters that were covered with coal dust. Additionally, he had a several‐year history of occupational skin exposure to machine oil, oil refinery waste, sulfur waste, hydraulic fluid, and asbestos. He also reported a history of nude sunbathing. His current medical problems include pleural asbestosis, poorly controlled type II diabetes, and congestive heart failure. His past dermatologic history includes intertrigo, onychomycosis, and an unknown skin lesion removed from the face 40 years ago. Recent clinical follow‐up and imaging studies, including chest X‐ray and bone scan, showed no evidence of visceral lesions, lytic bone lesions, or other signs of systemic involvement by Langerhans cell histiocytosis. The scrotal lesion was re‐excised and the patient remains disease‐free more than 1 year after the diagnosis.

Phakomatous choristoma is a rare congenital hamartoma of lens tissue. It presents in newborns or young infants as a subcutaneous mass in the medial lower eyelid. We present a case of phakomatous choristoma recently identified among old consultation files at Children's Hospital in Boston. Our case illustrates unique histological features of this entity which has to be included in differential diagnosis of skin lesions of the inferonasal eyelid.

Background:  During a clinical trial, we obtained 16 biopsies of skin eruptions induced by aspirin in patients with chronic idiopathic urticaria (CIU). In this setting, aspirin triggers skin eruptions through a well‐established non‐immunological mechanism involving the inhibition of cyclooxygenase type I. This presented the rare opportunity to evaluate histological features of a series of skin eruptions induced by a drug acting through a defined mechanism in a controlled experimantal setting.Objective:  Histological analysis of 16 biopsies of skin eruptions induced by oral aspirin challenge in patients with CIU.Design:  Microscopic analysis of tissue sections.Patients:  16 patients with CIU.Results:  Aspirin (up to 500 mg) induced a restricted range of histological responses with a classic pattern of urticarial tissue reaction occuring in the majority of (12 of 16) cases. Two biopsies showed an interstitial fibrohistiocytic (granuloma annulare‐like) reaction pattern. One case showed only a sparse perivascular lymphocytic infiltrate, and paucicellular dermal mucinosis was observed in one case.Conclusions:  Polymorphism of histological patterns induced by aspirin suggests that in addition to the drug‐specific mechanisms triggering drug eruptions, individual factors also play a role in determining the ultimate histological phenotype of a drug response.

Case Records of the Massachusetts General Hospital from The New England Journal of Medicine — Case 7-2004 — A 48-Year-Old Woman with Multiple Pigmented Lesions and a Personal and Family History of Melanoma

In the course of a study of borderline melanocytic tumors, we observed a distinctive group of lesions characterized by features very similar to those previously described in the literature as "animal-type melanoma" and epithelioid blue nevus of Carney complex. We have designated these lesions as pigmented epithelioid melanocytoma (PEM). Herein, we present a clinical-pathologic analysis of 41 consecutive PEM from 40 patients and compare them with 11 epithelioid blue nevi from patients with Carney complex. PEM occurred in both sexes of different ethnic backgrounds, including white, Hispanic, black, Asian, and Persian. The median age of occurrence was 27 years (range 0.6-78 years). Tumors had wide distribution with extremities being the most common site. The tumors were formed by deep dermal (mean Breslow's thickness 3.3 mm) proliferation of heavily pigmented epithelioid and/or spindled melanocytes. Five lesions were part of combined nevus. Ulceration was present in 7 cases. Tumor necrosis was present in 1 case. Regional lymph nodes were sampled in 24 cases (59%). In 11 cases, lymph nodes contained metastases (46%). Liver metastases occurred in 1 case. None of the patients died of disease. Clinical follow-up of more than a year (mean 32 months, range up to 67 months) was available in 27 cases (67%). We found no histologic criteria separating metastasizing and nonmetastasizing PEM. Ulceration was the only feature more common in PEM than epithelioid blue nevi of Carney complex. Otherwise, they were histologically indistinguishable. Our data show that PEM is a unique low-grade variant of melanoma with frequent lymph node metastases but indolent clinical course. We suggest that PEM be considered as a provisional histologic entity encompassing both animal-type melanoma and epithelioid blue nevus.

Research from JAMA Dermatology — Prevalence of Melanoma Clinically Resembling Seborrheic Keratosis — Analysis of 9204 Cases

Blue nevus and its variants typically present as pigmented lesions. Dermal melanin is responsible for coloration and is an expected histologic finding. Herein, we report 20 cases of an unusual amelanotic variant of cellular blue nevus . Our series showed clinical demographics similar to pigmented counterparts. Thus, there was a predilection for young individuals with a mean age of 24 years (range 6–74 years). Both sexes were affected, with a female-to-male ratio of approximately 2:1. The lower back, distal extremities, and scalp were the most common sites of occurrence. Importantly, the lack of pigmentation resulted in an atypical clinical appearance. A diagnosis of blue nevus by the attending physician was not considered in any of the reported lesions. All of the tumors extended deep into the reticular dermis or subcutaneous fat with a mean thickness of 5.5 mm (range 1.7–11 mm). Ulceration was present in two lesions. Mild cytologic atypia and pleomorphism were present in five cases. Mitotic activity (up to 3 mitoses/mm²) was observed in 11 lesions. A brisk lymphocytic host response was present in only one lesion. Tumor necrosis was not observed. Most, but not all, tumors showed reactivity for S-100 and HMB-45. Clinical follow-up (mean 32 months) was consistent with a benign course. Local recurrence was not observed after complete excision. None of the cases was associated with clinical evidence of lymph node or distant metastases. Recognition of amelanotic cellular blue nevus is important because the lack of expected pigmentation may result in clinical and pathologic diagnostic difficulty. In particular, amelanotic cellular blue nevus must be distinguished from malignant cellular blue nevus and other variants of melanoma.