Alopecia universalis with twenty-nail dystrophy (trachyonychia).

A 43-year-old man presented with long-standing trachyonychia of all 20 nails, which worsened after the onset of alopecia universalis 18 months ago. Trachyonychia can be associated with alopecia universalis although the treatment strategies of both conditions differ. The principle of treating trachyonychia may involve regulating the differentiation of keratinocytes and/or reducing inflammation in the nail fold or nail matrix while treatment of alopecia universalis involves immunomodulation.

Yellow nail syndrome.

A 70-year-old man presented with a three-year history of thickened and slow growing, yellow-to-green, discolored fingernails and toenails with loss of lunulae and cuticles. He also had a concurrent history of chronic sinusitis with persistent productive cough. His presentation was consistent with the diagnosis of yellow nail syndrome (YNS), which is a rare disorder classically characterized by the triad of yellow dystrophic nails, lymphedema, and respiratory tract abnormalities but which more frequently manifests with only two of three features. The exact mechanism of YNS remains unknown; however, it is thought to reflect functional and/or anatomic defects in the lymphatic vasculature. Treatment options are limited and often unsuccessful, but spontaneous remission occurs in approximately 30 percent of affected patients.

Oral lichen planus.

A 42-year-old woman presented with a 2-year history of persistent, gray-white lip discoloration and discomfort that had not improved after empiric treatment with topical 5-fluorouracil cream. Histopathologic examination demonstrated interface dermatitis with epidermal atrophy. A diagnosis of oral lichen planus was made based on clinicopathologic correlation, and treatment with topical tacrolimus ointment was initiated.

Nodular pretibial myxedema.

A 30-year-old man with previously diagnosed and treated Graves disease presented for consultation regarding asymptomatic nodules over his anterior tibias. He was euthyroid at the time of presentation. The nodules arose symmetrically beneath the sites of pressure from his military boots. A biopsy specimen showed an accumulation of acid mucopolysaccharides consistent with pretibial myxedema. The patient had recently stopped smoking and chewing tobacco, which are known risk factors for the development of pretibial myxedema. Following diagnostic punch biopsies, the patient experienced a rapid resolution of the nodule on his right leg and a appreciable reduction in size of the nodule on the left leg. Three months later, the nodules are beginning to enlarge once again.

A modified approach to the histologic diagnosis of onychomycosis.

BACKGROUND: Histologic examination of nail clippings with periodic acid-Schiff staining is the most sensitive diagnostic test for onychomycosis; however, difficulties in processing nail plates limit its use. In onychomycosis, fungi are most concentrated in the subungual hyperkeratosis rather than in the nail plate. We hypothesized that the diagnosis of onychomycosis could be effectively made from histologic examination of subungual hyperkeratosis alone. Specimens of subungual hyperkeratosis, unlike nail plates, can be processed in the same routine manner as skin specimens, allowing for the diagnosis of onychomycosis to be made more quickly and at lower cost. OBJECTIVE: We investigated whether the diagnosis of onychomycosis could be effectively made from histologic examination of subungual hyperkeratosis alone. METHODS: We selected all nail specimens submitted during an 8-month period to the New York University Dermatopathology Section for evaluation of onychomycosis that had subungual hyperkeratosis associated with the nail plate. Nail specimens were divided into two components: a subungual hyperkeratosis component and a nail plate component. The subungual hyperkeratosis was processed separately in a routine fashion and embedded in paraffin and examined. We determined the percentage of cases of onychomycosis in which hyphae were present in the subungual component. RESULTS: Sixty-six cases of onychomycosis were diagnosed histologically during the study period. Ninety-seven percent of these cases had hyphae in the subungual component. In 3% of cases, hyphae were present in the nail plate component but not in the subungual component. LIMITATIONS: This modified approach to diagnosing onychomycosis can only be utilized when an adequate amount of subungual hyperkeratosis is submitted. CONCLUSIONS: The diagnosis of onychomycosis can be effectively made from histologic examination of subungual hyperkeratosis alone in most cases. This method circumvents the need to process nail plates in the vast majority of cases of onychomycosis (97%), resulting in a more efficient, less costly, and technically easier way of diagnosing onychomycosis. Submitting ample amounts of subungual hyperkeratosis is essential to increasing the diagnostic yield of nail clippings.

Pigmented plexiform neurofibroma: Distinction from a large congenital melanocytic nevus.

The substantial clinical and histologic overlap between neurotized congenital melanocytic nevi and the subset of plexiform neurofibromas with hyperpigmentation and hypertrichosis of the overlying skin (pigmented neurofibroma) has led to considerable confusion in the literature. A dark-brown, hypertrichotic plaque covered much of the right lower aspect of the trunk of a 1-year-old girl with a diffuse and plexiform neurofibroma in the same area, numerous café-au-lait macules, and intertriginous freckling. The latter findings were diagnostic of neurofibromatosis-1, which was further supported by the presence of unidentified bright objects on magnetic resonance imaging of the brain. Histologic examination of the hyperpigmented plaque revealed melanocytic hyperplasia at the dermoepidermal junction and a proliferation of rounded, pigmented melanocytes dispersed individually and in occasional small nests in the papillary dermis and scattered within underlying neurofibromatous tissue. Immunohistochemical staining with A103 (Melan-A/MART-1) and PNL2 confirmed the melanocytic differentiation of the pigmented cells, whereas glial fibrillary acidic protein and Leu-7 were detected only within plexiform areas and slender neuroid spindle cells. This case draws attention to the pigmented neurofibroma as a distinct clinicopathologic entity resulting from proliferation of melanocytes and neurosustentacular cells in the setting of neurofibromatosis-1.

Lepromatous leprosy.

A 51-year-old woman presented with a 2-month history of pruritic, erythematous papules and plaques on her arms that were treated as chronic urticaria. Histopathologic examination demonstrated acid-fast bacilli, and a diagnosis of lepromatous leprosy was made. Presentation and treatment of leprosy are reviewed.

Brooke-Spiegler syndrome.

A 46-year-old woman with Brooke-Spiegler syndrome has multiple cutaneous adnexal neoplasms on her face and scalp. One of the lesions has concurrent features of cylindroma, trichoepithelioma, and spiradenoma in the same specimen. Etiology, clinical features, malignant transformation, and treatment modalities for Brooke-Spiegler syndrome are reviewed.

Primary cutaneous B-cell lymphoma (low-grade, non large cell).

A 43-year-old man presented with erythematous, indurated plaques on the scalp in the setting of a 16-year history of recurrent cutaneous tumors of the head and trunk. Clinical and histopathologic findings were consistent with a diagnosis of primary cutaneous B-cell lymphoma. Laboratory data and computed tomography imaging of the chest, abdomen, and pelvis failed to show an associated systemic lymphoma. Primary cutaneous B-cell lymphomas are a heterogenous group of lymphomas that primarily involve the skin but have variable clinical, histopathologic, and immunologic phenotypes. Successful treatment for most localized subtypes consists of surgical excision and radiation therapy. Rituximab, a chimeric monoclonal antibody that binds the B-cell-specific antigen CD20, has shown promise in treating a number of primary cutaneous B-cell lymphomas.

Glomuvenous malformations.

A 9-year-old girl presented with a congenital, blue-purple, partially compressible plaque with a cobblestone surface on the left lateral foot and ankle. Similar, solitary, blue nodules later appeared elsewhere on the extremities. The lesions were tender to palpation and were associated with spontaneous paroxysms of pain and paresthesias. Histopathologic evaluation of a skin biopsy specimen showed rows of glomus cells that surrounded thin-walled vascular channels, which confirmed the diagnosis of glomuvenous malformations. This autosomal dominant condition, which is due to mutations in the GLMN gene, presents with clinical findings that are distinct from those of familial, multiple, cutaneous and mucosal venous malformations. Treatment options include excision, sclerotherapy, and laser therapy (ablative or pulsed dye).

Mycosis fungoides with depigmentation secondary to treatment.

A 51-year-old man presented with itchy, erythematous patches and plaques on his trunk, arms, and legs. A skin biopsy specimen showed mycosis fungoides. Initially the patient did not respond to PUVA photochemotherapy but later improved on NB-UVB phototherapy combined with bexarotene and interferon-alpha. The lesions progressed from erythematous patches and plaques to hyperpigmented patches with central depigmentation and localized areas of follicular repigmentation. The development of depigmentation after PUVA photochemotherapy for mycosis fungoides has been described in the literature and does not have associated prognostic implications. It is important to be cognizant of phototoxicity associated with PUVA photochemotherapy or NB-UVB phototherapy in patients with mycosis fungoides, who may be taking photosensitizing medications or have depigmented patches which renders them more sensitive to lower doses of ultraviolet light.

Mutations in the desmoglein 4 gene underlie localized autosomal recessive hypotrichosis with monilethrix hairs and congenital scalp erosions.

Localized autosomal recessive hypotrichosis (LAH) is a recently defined disorder characterized by fragile, short, sparse hairs on the scalp, trunk, and extremities. Mutations in desmoglein 4 (DSG4), a novel member of the desmosomal cadherin family that is expressed in the hair follicle as well as the suprabasal epidermis, have been found to underlie LAH. Thus far, the allelic series includes a recurrent intragenic deletion identified in affected Pakastani kindreds and a missense mutation detected in an Iraqi family. We report three siblings of Iraqi and Iranian origin with LAH that presented with congenital scalp erosions and monilethrix-like hairs, features that have not been previously described in this disorder. Follicular hyperkeratotic papules and marked pruritus were also prominent clinical findings. Novel compound heterozygous DSG4 mutations, including a splice-site mutation and a missense mutation that disrupts a conserved calcium-binding site in the extracellular (EC)2-EC3 interface, were found to underlie the disease in this family. These observations broaden the phenotypic and genotypic spectrum of LAH, further illustrating the consequences of DSG4 dysfunction on epidermal and hair shaft integrity.

Generalized granuloma annulare.

A 94-year-old man presented with a relatively asymptomatic eruption of his forearms, abdomen, and back comprising symmetric erythematous papules and plaques. Generalized granuloma annulare is an idiopathic disorder that occurs more commonly in older patients and is characterized by numerous flesh-colored-to-erythematous papules. It is distinguished histologically by palisading granulomas with central connective tissue degeneration and with central mucin. Therapy has been attempted with various modalities with moderate efficacy.

Nevus sebaceus.

A 35-year-old woman presented with cosmetically disturbing facial plaques, which had been present since birth and were consistent with nevus sebaceus on histopathologic examination. Nevus sebaceus is a congenital, hairless plaque, which is found most commonly on the scalp and face and typically becomes thicker and more verrucous in appearance as the patient enters adulthood. There is an association with benign and malignant neoplasms. Typically, these lesions are either removed surgically or the patients are followed clinically. Other therapeutic modalities utilized for cosmesis include carbon dioxide laser and photodynamic therapy.

Acquired perforating disorder.

A 53-year-old man presented with asymptomatic, hyperkeratotic papules and hyperpigmented macules of the face and upper extremities. Treatment was initiated with topical tretinoin and intralesional glucocorticoids. Acquired perforating disorder is a disorder of keratinization that is associated with diabetes mellitus and uremia. Classic presentation involves hyperkeratotic papules with a central core, which occur most frequently on the lower extremities. Treatment includes topical tretinoin, glucocorticoids, keratolytics, systemic retinoids and glucocorticoids, and ultraviolet B phototherapy.

Cowden's syndrome.

A 59-year-old woman initially presented with facial papules, which were consistent with trichilemmomas on histopathologic examination. Her course was complicated by breast, endometrial, and renal-cell carcinomas, as well as a multinodular goiter that necessitated a thyroidectomy. Cowden's syndrome is a rare autosomal dominant syndrome that is characterized by hamartomas of ectodermal, mesodermal, and endodermal origin as well as an increased risk of breast, thyroid, and endometrial neoplasias. Medical management includes screening for breast cancer and thyroid abnormalities, and performing other age-specific examinations. Treatment of facial papules includes topical 5-fluorouracil, isotretinoin, curettage, laser ablation, or surgical excision.

Granulomatous cheilitis.

A 54-year-old man presented with lip swelling, which was not altered by a trial of medication discontinuation. Patch tests showed reactions to bromonitropropane and gold, which were not clinically relevant. Treatment included topical and intralesional glucorticoids as well as tacrolimus ointment. Granulomatous chelitis an idiopathic disorder that is characterized by painless lip edema. It may be found as part of the triad of Melkersson-Rosenthal syndrome. Treatment includes intralesional glucocorticoids as well as systemic therapies.

Clinical pathologic correlations for diagnosis and treatment of nail disorders.

Clinicopathologic correlation is crucial to the correct diagnosis of disorders of the nail unit. This chapter will explore four common clinical scenarios and how pathology can help differentiate between their various etiologies. These include: dark spot on the nail plate (melanin versus heme), subungual hyperkeratosis (onychomycosis versus psoriasis), longitudinal melanonychia (benign versus malignant), and verrucous papule (verruca versus squamous cell carcinoma). Consideration must be given to both when to perform a biopsy and the location of the biopsy site, which must be based on an understanding of the origin of the changes. An overarching principle is that lesions within the same differential diagnosis may be present concomitantly, such as malignant melanoma of the nail unit associated with hemorrhage. Therefore, even with a biopsy-proven diagnosis, the clinician must always monitor lesions of the nail unit for appropriate response to treatment and consider an additional biopsy for recalcitrant lesions.

Thrombotic complications related to discontinuation of warfarin and aspirin therapy perioperatively for cutaneous operation.

BACKGROUND: Aside from anecdotal reports, there are few data on the risk of thrombotic complications in patients in whom use of warfarin and aspirin is discontinued perioperatively for cutaneous operation. OBJECTIVE: Our aim was to present a large case series of thrombotic complications resulting from this practice and to estimate the incidence of these events. METHODS: A total of 504 members of the American College of Mohs Micrographic Surgery and Cutaneous Oncology were surveyed regarding thrombotic complications when blood thinners were withheld perioperatively to ascertain the frequency of these complications and to describe associated morbidity and mortality. RESULTS: A total of 168 responding physicians reported 46 patients who experienced thrombotic events. Of these patients, 54% (25 of 46) experienced the event when warfarin was withheld and 39% (18 of 46) when aspirin use was discontinued. Thrombotic events included 24 strokes, 3 cerebral emboli, 5 myocardial infarctions, 8 transient ischemic attacks, 3 deep venous thromboses, 2 pulmonary emboli, and 1 retinal artery occlusion leading to blindness. Three deaths were reported. Calculation of incidence yielded an estimated thrombotic risk of 1 event per 12,816 operations, 1 in 6219 operations when use of warfarin was discontinued and 1 in 21,448 when aspirin was withheld. CONCLUSIONS: With no documented increase in severe hemorrhagic complications during continued use perioperatively of blood thinners, these data provide a compelling argument to maintain patients on medically necessary blood thinners during cutaneous operation. All relevant clinical facts must be weighed when making this decision.