Case records of the Massachusetts General Hospital. Case 2-2007. A 49-year-old woman with a pigmented lesion on the arm.
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Biomedical subjects
Publications and source records attributed to Artur Zembowicz.
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UNLABELLED: Paraneoplastic dermatoses comprise a heterogeneous group of noninherited skin conditions that manifest internal malignancy. Familiarity with paraneoplastic dermatoses is important to both clinician and pathologist alike, as recognition of such a condition offers opportunity for early diagnosis and treatment of internal malignancy; monitoring for tumor recurrence; and insight into pathophysiology which may yield possible clues to treatment. Herein are reviewed 16 of the best established paraneoplastic dermatoses that display distinctive clinical and pathologic findings. LEARNING OBJECTIVE: At the conclusion of this leaning activity, participants should be able to recognize, diagnose, and describe the clinical and pathologic findings of paraneoplastic dermatoses.
BACKGROUND: Rare cases of a non-bullous neutrophilic dermatosis occurring in patients with lupus erythematosus (LE) have been reported, often as the presenting manifestation of the disease. METHODS: We reviewed hematoxylin and eosin-stained slides and obtained clinical information from four additional patients, two of whom had no prior history of LE. RESULTS: All patients were female, aged 16-59 (mean age 37). Clinically, the skin lesions were characterized by widely distributed pruritic papules and plaques. Three patients presented with systemic symptoms, including fever, arthritis and malaise. Histopathologic examination in all cases showed a superficial perivascular and interstitial neutrophilic infiltrate with leukocytoclasis. There was no evidence of vasculitis. Mild focal vacuolar change was a subtle feature seen only in the biopsies of the two patients with a prior history of LE. CONCLUSIONS: It is important to consider LE in the differential diagnosis of non-bullous neutrophilic dermatoses.
Histologic differentiation between basal cell carcinoma and benign trichoblastic neoplasms such as trichoepithelioma and trichoblastoma can be difficult on small biopsies. Therefore, several attempts have been made to identify immunohistochemical differences between these entities. Recent studies have shown androgen receptor expression in a number of mature epithelial structures in the skin and in epithelial neoplasms including basal cell carcinoma. In contrast, androgen receptor expression was absent in mature hair follicles or the few trichogenic neoplasms studied to date. These findings suggested that androgen receptor expression might be a useful adjunct in the histologic differential diagnosis between basal cell carcinoma and benign trichoblastic neoplasms. Therefore, we performed immunohistochemical analysis of androgen receptor expression in 32 basal cell carcinomas and 10 benign trichoblastic tumors (6 trichoepitheliomas and 4 trichoblastomas). In our study, at least focal expression of androgen receptor was detected in 78% of basal cell carcinomas. None of the trichoblastic tumors showed any androgen receptor immunoreactivity. These results confirm the lack of expression of androgen receptor in benign trichoblastic neoplasms and indicate that androgen receptor expression by tumor cells points to basal cell carcinoma as the most likely diagnosis.
Cutaneous metastasis of follicular carcinoma of the thyroid is very rare, and when it occurs, can exhibit a variety of histologic appearances. The 4 cases presented here were identified from the surgical pathology files of the James Homer Wright Laboratories of Pathology at the Massachusetts General Hospital (MGH). The cases consisted of 4 patients, 3 men and 1 woman, aged 52 to 75 years, with cutaneous metastasis of follicular thyroid carcinoma. The tumors include a conventional follicular carcinoma, a follicular carcinoma with anaplastic transformation following initial metastasis, the first reported cutaneous metastases of a follicular carcinoma with oncocytic features (Hürthle cell carcinoma), and a follicular carcinoma with a prominent insular carcinoma component. All 4 tumors were widely invasive within the thyroid gland. Sites of dermal metastases included a post-thyroidectomy scar, scalp, and sacral skin. Three metastases retained the morphologic and immunocytochemical features of the primary thyroid tumors. However, in one case there was high-grade transformation to anaplastic carcinoma following treatment of a sacral metastasis with accompanying loss of the characteristic immunophenotype of follicular thyroid carcinoma. Awareness of the varied morphologies of metastatic follicular thyroid carcinoma to the skin may prompt immunohistochemical analysis and the request for a complete clinical history, ultimately preventing misdiagnosis.
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.
BACKGROUND: Endocrine mucin-producing sweat gland carcinoma is a very rare cutaneous tumor that has been reported only in three patients previously. We report a case of an endocrine mucin-producing sweat gland carcinoma associated with mucinous carcinoma treated by Mohs' micrographic surgery. OBJECTIVE: The purpose of this report is to test the utility of Mohs' micrographic surgery in the treatment of mucinous carcinomata. METHODS: A 79-year-old female with a 2-year history of four lesions of biopsy-proven endocrine mucin-producing sweat gland carcinomas and mucinous carcinoma was treated with Mohs' micrographic surgery. RESULTS: Three of the lesions were completely cleared by Mohs' micrographic surgery. The fourth lesion, in the right lateral canthus, was not cleared by the Mohs' technique because of its location within the orbit and the difficulty of retraction of the globe for appropriate visualization and excision. The patient underwent wide excision of the remaining orbital tumor and reconstruction, which was successfully accomplished. The patient did not experience a recurrence in any of her four lesions over a 2-year follow-up period. CONCLUSION: Mohs' micrographic surgery is an appropriate treatment for mucinous carcinomata, including endocrine mucin-producing sweat gland carcinoma and mucinous carcinoma.
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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.
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 experimental 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 occurring 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.
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BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) exacerbate various forms of urticaria by a nonallergic mechanism involving inhibition of cyclooxygenases. OBJECTIVES: To assess safety of cyclooxygenase inhibitors in patients with chronic idiopathic urticaria (CIU) and NSAID sensitivity and to evaluate a role of cysteinyl leukotriene metabolism and mast cell activation in sensitivity to NSAIDs in CIU. DESIGN: Aspirin challenge test followed by randomized, prospective, double-blind, placebo-controlled crossover trial with cyclooxygenase 2 inhibitors. SETTING: Tertiary referral center of a university hospital. PATIENTS: Thirty-six patients with CIU. INTERVENTIONS: Aspirin challenge test (up to 500 mg); randomized trial with rofecoxib (up to 37.5 mg) and celecoxib (up to 300 mg) in aspirin-sensitive patients. After completion of the trial, 7 patients received naproxen sodium (500 mg) as a positive control. MAIN OUTCOME MEASURES: Standardized skin examination, skin biopsy with mast cell count, urinary levels of leukotriene E4 (LTE4), and serum levels of mast cell tryptase. RESULTS: Aspirin induced skin eruption in 18 patients. Rofecoxib or celecoxib did not elicit skin eruption in any of the aspirin-sensitive patients. Patients with CIU had higher urinary excretion of LTE4 than healthy control subjects. Basal urinary levels of LTE4 and serum mast cell tryptase were increased in aspirin-sensitive compared with aspirin-tolerant patients. Severity and duration of aspirin-induced urticaria showed a positive correlation with urinary LTE4 excretion. Naproxen precipitated urticaria in 5 of 7 aspirin-sensitive patients and caused further increase in urinary LTE4. CONCLUSIONS: Cyclooxygenase 2 inhibitors do not induce urticaria in patients with CIU sensitive to NSAIDs. Sensitivity to NSAIDs in CIU is associated with overproduction of cysteinyl leukotrienes and mast cell activation and most likely depends on inhibition of cyclooxygenase 1.
Although fine-needle aspiration biopsy (FNAB) is a highly accurate tool for the diagnosis of pleomorphic adenomas, even this common salivary gland neoplasm can be diagnostically challenging and cause pitfalls in cytodiagnosis. In particular, the presence of either cystic degeneration or squamous and mucinous metaplasia can lead to a false positive diagnosis of malignancy. Here we present the case of a 16-year-old female who presented with a painless, slowly growing mass in the superficial lobe of the right parotid gland. Magnetic resonance imaging of the parotid demonstrated a mass with heterogeneous postcontrast enhancement and a central, nonenhancing area suggestive of necrosis. FNAB of the lesion yielded proteinaceous debris and numerous whorls of keratin, small cohesive clusters of basaloid and squamoid epithelial cells, and many vacuolated and foamy cells. Initially and after consultation at an outside institution, the FNAB was reported as an "atypical neoplasm, cannot exclude mucoepidermoid carcinoma." A total, nerve-sparing parotidectomy and level II neck dissection revealed a pleomorphic adenoma with central cystic degeneration and extensive mixed appendageal differentiation. While foci of squamous metaplastic changes may occur in pleomorphic adenomas, the combination of cystic degeneration and extensive appendageal differentiation with numerous keratotic cysts is rare, and it presents the potential for misinterpretation of the FNAB as indicative of malignancy in general, and mucoepidermoid carcinoma in particular.
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OBJECTIVE: To estimate the prevalence of melanoma clinically mimicking seborrheic keratosis. DESIGN: Retrospective review of cases submitted for histological examination with a clinical diagnosis of seborrheic keratosis or with a differential diagnosis that included seborrheic keratosis. SETTING: A tertiary medical care center-based dermatopathology laboratory serving academic dermatology clinics that have a busy pigmented lesion clinic. MATERIALS AND METHODS: A total of 9204 consecutive pathology reports containing a diagnosis of seborrheic keratosis in the clinical information field were identified between the years 1992 and 2001 through a computer database search. Reports with a final histological diagnosis of melanoma were selected for further review and clinicopathological analysis. MAIN OUTCOME MEASURE: Histological diagnosis, which was correlated with the preoperative clinical diagnosis. RESULTS: Melanoma was identified in 61 cases (0.66%) submitted for histological examination with a clinical diagnosis that included seborrheic keratosis. Melanoma was in the clinical differential diagnosis of 31 cases (51%). The remaining lesions had a differential diagnosis of seborrheic keratosis vs melanocytic nevus (17 cases, 28%), basal cell carcinoma (7 cases, 12%), or a squamous proliferation (3 cases, 5%). In 3 cases (5%), seborrheic keratosis was the only clinical diagnosis. All histological types of melanoma were represented. CONCLUSIONS: Our results confirm that melanoma can mimic seborrheic keratosis. These data strongly support the current policy of submitting for histological examination all specimens that have been removed from patients.