Tuesday, August 31, 2010
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Cutaneous CD34+ Spindle Cell Neoplasms: Histopathologic Features Distinguish Spindle Cell Lipoma, Solitary Fibrous Tumor, and Dermatofibrosarcoma Protuberans.Am J Dermatopathol. 2010 Jun 17.
Spindle cell lipoma (SCL), dermatofibrosarcoma protuberans (DFSP), and solitary fibrous tumors (SFT) are cutaneous CD34+ spindle cell tumors that may exhibit histopathologic and immunophenotypic overlap. We sought ways to reliably distinguish among these lesions even in small or superficial biopsies. Ten morphologic characteristics were analyzed in a group of 5 SCLs, 6 cutaneous SFTs, and 12 DFSPs. SFT and DFSP exhibited extensive histopathologic overlap in small or partial biopsies. However, adnexal entrapment, defined as diffuse proliferation of tumor cells around pilosebaceous and eccrine structures with minimal disruption or expansion of the dermis, was a feature seen in 10 of the 12 DFSPs and in none of the SFTs or SCLs. Even when only superficial portions of a lesion were present, this feature was identifiable. Spindle cell lipomas posed little diagnostic difficulty, in part because excisional biopsies were performed in all cases of SCL. The number of samples included in the study is relatively small, in part due to the rarity of cutaneous solitary fibrous tumors. We conclude that careful attention to these histopathologic features enables reliable distinction among these tumors.
Dermatofibrosarcoma protuberans: how wide should we resect?Ann Surg Oncol. 2010 Aug;17(8):2112-8. Epub 2010 Mar 31.
BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare dermal tumor with local recurrence rates ranging from 0 to 50%. Controversy exists regarding margin width and excision techniques, with some advocating Mohs surgery and others wide excision (WE). We reviewed the experience in two tertiary centers using WE with total peripheral margin pathologic evaluation.MATERIALS AND METHODS: Institutional Review Board approved retrospective review of patients with DFSP from 1991 to 2008. Patients had initial WE using 1-2 cm margins with primary or delayed closure; further excision was done whenever feasible for positive margins. Pathologic analysis included en face sectioning. We evaluated margin width, number of WE, reconstruction methods, radiation, and outcomes.RESULTS: A total of 206 DFSP lesions in 204 patients (76 males, 128 females), median age 41 years (range 1-84) were treated. Locations were trunk (135), extremities (43), and head and neck (28). The median number of excisions to achieve negative margins was 1 (range 1-4) with a median excision width of 2 cm (range 0.5-3 cm). Closure techniques included primary closure (142; 69%), skin grafting (52; 25%), and tissue flaps (9; 4%). There were 9 patients who received postoperative radiation, 6 for positive margins after maximal surgical excision. At a median follow-up of 64 months (range 1-210), 2 patients (1%) with head and neck primaries recurred locally.CONCLUSIONS: Using a standardized surgical approach including meticulous pathologic evaluation of margins, a very low recurrence rate (1%) was achieved with relatively narrow margins (median 2 cm), allowing primary closure in 69% of patients. This approach spares the additional morbidity associated with wider resection margins and in our experience represents the treatment of choice for DFSP occurring on the trunk and extremities.
Dermatofibrosarcoma protuberans in the breast of a 2-year-old girl.Ann Diagn Pathol.2010 Aug;14(4):279-83. Epub 2009 Dec 1.
Dermatofibrosarcoma protuberans (DFSP) is a low-grade dermal and subcutaneous spindle cell neoplasm that most commonly occurs in the extremities and trunk of adults. It is rare in children and infants, and only few cases are reported as congenital. A 2-year-old girl presented with a rapidly enlarging left breast mass. The histology of the excised mass revealed a moderately cellular spindle cell tumor with large hypercellular fibrosarcoma-like areas, few myxoid areas, and other areas with multinucleated giant cells. By immunohistochemistry, the tumor cells were focally positive for CD34 and were negative in the fibrosarcomatous areas. The diagnosis of DFSP was confirmed by demonstrating an unbalanced translocation der(22)t(17;22)(q21.3;q13.1) by conventional cytogenetic and fluorescence in situ hybridization analyses. Positive immunoreactivity with PDGFR-beta antibody indicated constitutional activation of PDGF receptor and provided an alternate indirect method of confirming the presence of dysregulated PDGF gene involved in this translocation. Although DFSP has been described in the adult female breast, this is the first such case in the breast of a 2-year-old girl. Dermatofibrosarcoma protuberans should be considered in the differential diagnosis of subcutaneous/dermal spindle cell tumors in children regardless of the site. CD 34 immunostaining should not be relied on, as it may be negative in fibrosarcomatous areas. Confirmation of the diagnosis in unusual sites requires identification of the characteristic t(17;22) chromosomal translocation.
Dermatofibrosarcoma protuberans of the vulva: a clinicopathologic and immunohistochemical study of 13 cases. Am J Surg Pathol. 2010;34(3):393-400.
Dermatofibrosarcoma protuberans (DFSP) is a low-grade sarcoma seldom seen in the vulva with only 29 cases reported. We present the clinicopathologic and immunohistochemical features of 13 such cases seen in our institution over a period of 29 years (1978 to 2007). Patient age ranged from 23 to 76 years (mean, 46 y). Twelve patients had a vulvar mass. One patient presented with a pigmented skin lesion. Tumor size ranged from 1.2 to 15 cm (median, 4 cm). Microscopically, all the cases showed typical features of DFSP. In 1 case, myxoid changes were also noted; 3 cases showed fibrosarcomatous transformation. Of interest, in 7 of our 13 cases, a variety of diagnoses, such as cellular dermatofibroma, cellular leiomyoma, neurofibroma, low-grade leiomyosarcoma, fibrosarcoma, low-grade malignant schwannoma, desmoplastic melanoma, cellular neurofibroma, and low-grade malignant peripheral nerve sheet tumor were initially considered. All 11 cases tested for CD34 were positive, whereas 7/9 cases, 8/9 cases, and 9/9 cases were positive for PDGFR-alpha, PDGFR-beta, and c-abl, respectively. All patients were initially treated with excisional biopsy, wide local excision, or radical vulvectomy. Local recurrences occurred in 7 cases. One patient also developed distant metastases. All recurrences were treated surgically; 1 patient also received chemotherapy and radiotherapy and another received imatinib (Gleevec). Follow-up data ranging from 2 to 444 months was available for all patients. Nine patients had no evidence of disease, 2 patients were alive with disease, 1 patient had died of disease, and 1 patient had died of other causes. DFSP affects women of a wide age range and has a propensity to recur locally. The frequent expression of PDGFR-alpha, PDGFR-beta, and c-abl in these cases agrees with the findings of other investigators and supports the use of imatinib (Gleevec) in cases that are recurrent or not amenable to surgery.
Plaque-like CD34-positive dermal fibroma ("medallion-like dermal dendrocyte hamartoma"): clinicopathologic, immunohistochemical, and molecular analysis of 5 cases emphasizing its distinction from superficial, plaque-like dermatofibrosarcoma protuberans.Am J Surg Pathol.2010 Feb;34(2):190-201.
We analyzed the clinical, histomorphologic, and molecular criteria of 5 DH and 7 DFSP to delineate diagnostically relevant differences between incipient dermal DFSP and its benign look-alike, DH. We expand the clinical and histologic spectrum of DH. As medallion-like dermal DH is neither of dermal dendrocyte lineage nor a genuine hamartoma, we propose instead the descriptive term of plaque-like CD34-positive dermal fibroma (PDF). Both PDF/DH and DFSP presented as slightly pigmented and indurated plaques on neck, trunk, and extremities. Histologically, DFSP was characterized either by horizontally oriented spindle cell fascicles or by diffusely arranged fibroblasts within a slightly myxoid stroma in the upper two-thirds of the dermis, whereas PDF/DH presented with a cellular band-like fibroblastic proliferation mostly in the papillary and adjacent upper reticular dermis. Only one congenital PDF/DH in a 9-year-old boy extended into the septa of the subcutaneous fat. Formalin-fixed paraffin-embedded archival tissue was used for detection of the COL1A1-PDGFB gene rearrangement by multiplex reverse transcription-polymerase chain reaction (RT-PCR) and by dual color fusion fluorescence in-situ hybridization (FISH). Archival blocs older than 4 years did not yield amplifiable RNA because of RNA degradation, whereas FISH analysis was feasible in all investigated cases. FISH analysis revealed COL1A1-PDGFB gene rearrangement in all DFSP cases (n=7), whereas RT-PCR could detect the COL1A1-PDGFB fusion transcript only in 1 DFSP. Two cases were negative. In 4 archival cases with storage between 4.5 and 12 years, RNA had been degraded making these cases unsuitable for RT-PCR. In PDF/DH, both RT-PCR and FISH analysis did not reveal any evidence of COL1A1-PDGFB gene rearrangement. We show that PDF/DH and superficial (plaque-like) DFSP, subtle clinicopathologic differences notwithstanding, are morphologic look-alikes that can be kept apart by molecular studies of the COL1A1-PDGFB gene fusion. For the detection of the COL1A1-PDGFB gene rearrangement in diagnostically difficult cases, RT-PCR and FISH analysis are reliable and helpful diagnostic tools. In archival formalin-fixed paraffin-embedded tissue, however, FISH analysis is more robust and exhibits a higher clinical sensitivity than RT-PCR.
Sunday, August 22, 2010
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Visit: Pathology of Cutaneous Sarcoidosis
Sarcoidosis of the skin--a dermatological puzzle: important differential diagnostic aspects and guidelines for clinical and histopathological recognition. J Eur Acad Dermatol Venereol.2010 Feb;24(2):125-37. Epub 2009 Aug 17.
Sarcoidosis of the skin may have an extremely heterogeneous clinical presentation, so that the definitions of 'great imitator' and 'clinical chameleon' have long been used. There is, in fact, a large group of skin diseases that can enter the differential diagnosis with cutaneous sarcoid manifestations, either clinically or/and pathologically. As the clinical consequences and the prognosis of these groups of diseases are often very different, it is important to correctly plan the diagnostic workup. The diagnostic process in this case often presents a challenge as no single test is sufficiently specific, so that a certain diagnosis can be only made in the presence of a compatible clinical and radiographic picture, along with histopathological evidence of non-necrotizing, epithelioid cell granulomas, and exclusion of other potential aetiologies. For practical reasons, four main groups of skin conditions capable of mimicking sarcoidosis can be identified: (i) transmissible, infectious diseases; (ii) allergic and immunological manifestations of various aetiologies; (iii) granulomatous diseases of various aetiologies; and (iv) lymphomas and pseudolymphomas. The aim of this article is to describe the main clinical and histopathological findings of such disease entities, and to discuss the role of those features (morphological, pathological and laboratory) that can help distinguish them from sarcoidosis of the skin.
Cutaneous sarcoidosis.Semin Respir Crit Care Med. 2010 Aug;31(4):442-51. Epub 2010 Jul 27.
Sarcoidosis is a systemic disease with skin manifestations. Skin manifestations are classified as nonspecific if they are not characterized by granulomatous inflammation and specific if the lesions have granulomas histologically. Erythema nodosum is the most common nonspecific skin manifestation, and it portends a good prognosis. Specific skin lesions have a varied clinical appearance, although often they can be distinguished by their yellow translucent character. Despite the potential variable appearance, there are common clinical presentations. Lupus pernio lesions are nodular violaceous specific skin lesions found predominantly on the face associated with scarring and a poor prognosis. Treatment of cutaneous sarcoidosis is primarily done to avoid scarring and cosmetic disfigurement. Local and systemic corticosteroids are the mainstay of treatment for the disease. Corticosteroid-sparing agents used to manage the disease include antimalarials, methotrexate, and tetracycline antibiotics. Tumor necrosis factor-alpha (TNF-alpha) antagonists such as infliximab may have a role in cutaneous sarcoidosis, especially in refractory cases that are resistant to the standard regimens.
Cutaneous sarcoidosis presenting as multiple erythematous macules and patches.Ann Dermatol. 2009 May;21(2):168-70. Epub 2009 May 31.
Sarcoidosis is an idiopathic multisystemic disorder with variable cutaneous presentations that are classified as specific or non-specific according to the presence of non-caseating granulomas on histologic examination. Specific manifestations can include papules, scar sarcoidosis, ulcers, or even alopecia. Herein, we present a case of cutaneous sarcoidosis that presented as multiple erythematous macules and patches on the trunk and extremities of a 32-year-old man. The clinical appearance was unlike any other form reported in the literature.
Cutaneous sarcoidosis: the "great imitator": etiopathogenesis, morphology, differential diagnosis, and clinical management.Am J Clin Dermatol.2006;7(6):375-82.
Sarcoidosis is a multisystem disease that can involve almost any organ system. The underlying cause of the disease remains unknown. Immunopathologically and histologically, cutaneous sarcoidosis is characterized by a macrophage/T helper-1 cell-mediated, non-caseating, granulomatous inflammation process. An imbalance between proinflammatory and anti-inflammatory cytokines plays an important role in the development of cutaneous granulomas. Recognition of cutaneous sarcoidosis lesions is very important because they provide a visible clue to the diagnosis and are an easily accessible source of tissue for histologic examination. Because skin lesions of patients with the disease can exhibit many different morphologies, cutaneous sarcoidosis is known as one of the "great imitators" in dermatology. Specific manifestations can include patches (sometimes hypopigmented), papules, scar sarcoidosis, ulcers, ichthyosis, and alopecia. The treatment of cutaneous sarcoidosis is often frustrating because some of the skin lesions may be refractory to treatment or may recur following successful treatment. Systemic and topical corticosteroids are the most effective treatments for cutaneous sarcoidosis. This article focuses on the dermatologic aspects of sarcoidosis and includes a review of the most recent literature, which includes new data on the diagnosis, differential diagnosis, pathogenesis, and treatment of the disease.
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Chondroid syringoma: a rare tumor of the chest wall. Ann Thorac Surg.2010 Mar;89(3):983-5.
Chondroid syringoma, an uncommon, slow-growing, benign, sweat-gland tumor located on the upper right chest wall of a 66-year-old woman is presented. This skin adenexal tumor is typically located on the head and neck region. The unusual location of chondroid syringoma made an accurate preoperative diagnosis difficult, and diagnosis was achieved only by excisional biopsy and histopathologic examination. Total surgical excision remains the best therapeutic option to avoid tumor recurrence and close follow-up is recommended because of a rare possibility of malignant transformation and visceral metastases.
Chondroid syringoma of the hand.Scand J Plast Reconstr Surg Hand Surg.2009;43(5):291-3.
Chondroid syringoma is a rare cutaneous tumour that usually arises in the head and neck region and is rarely seen on the hands; it is rarely malignant at sites other than the head and neck. However, it should be included in the differential diagnosis of tumours of the hand. We present a 56-year-old man with a chondroid syringoma of the hand that clinically resembled a vascular tumour.
Chondroid syringoma with tyrosine crystals: case report and review of the literature.Am J Dermatopathol.2010;32(2):171-4.
Chondroid syringoma (CS) is a relatively rare cutaneous mixed tumor arising from sweat glands. It usually presents in the head and neck area as an asymptomatic, slow-growing, firm, circumscribed, lobulated nodule within the dermis or subcutaneous fat. CSs share morphologic similarities with their salivary gland counterparts, pleomorphic adenomas (benign mixed tumors). Although the presence of tyrosine-rich crystalloids in mixed tumors of the salivary gland is well recognized, to our knowledge, this finding has not been previously described in mixed tumors of the skin. We report a case of tyrosine crystalline structures in a CS and review the pertinent literature.
Apocrine mixed tumor of the skin ("mixed tumor of the folliculosebaceous-apocrine complex"). Spectrum of differentiations and metaplastic changes in the epithelial, myoepithelial, and stromal components based on a histopathologic study of 244 cases.J Am Acad Dermatol.2007 Sep;57(3):467-83.
BACKGROUND: A systematic analysis of the entire spectrum of various forms of differentiation and metaplastic epiphenomena in cutaneous apocrine mixed tumor (AMT) has never been performed.
OBJECTIVE: The purpose of our study was to study a large number of cutaneous mixed tumors so as to fully characterize the entire spectrum of differentiations and metaplastic changes that may occur in the epithelial, myoepithelial, and stromal components of AMT.
METHODS: This article reports a light-microscopic study of 244 cases of cutaneous AMT, complemented by a literature review.
RESULTS: All types of differentiation along the lines of the folliculosebaceous-apocrine unit can be seen in AMT. The spectrum of metaplastic changes in the epithelial components includes squamous metaplasia, mucinous metaplasia, oxyphilic metaplasia, clear cell change, columnar metaplasia, hobnail metaplasia, and cytoplasmic vacuolization. The following changes in the myoepithelial component were documented: clear cell change, hyaline cells, plasmacytoid cells, spindling, and collagenous spherulosis. Stromal alterations included chondroid metaplasia, osseous metaplasia, and adipose metaplasia.
LIMITATIONS: This study utilizes tissue specimens that mainly came as consultations; therefore some inherent selection bias exists.
CONCLUSIONS: AMT displays a wide range of differentiation and metaplastic changes in its epithelial, myoepithelial, and stromal components. These phenomena are not mutually exclusive. When unduly prominent, they may present diagnostic pitfalls. Our findings corroborate those of previous publications, stressing the remarkable diversity of differentiation and metaplasias that may be found in cutaneous AMT. We propose that the most appropriate name for these lesions is "mixed tumor of the folliculosebaceous-apocrine complex."
Chondroid syringoma: case report and review of the literature.Dermatol Online J.2006 Sep 8;12(5):8.
An 84-year-old man presented with an enlarging bluish, painless subcutaneous nodule on the glabella. The lesion had been excised 4 years prior and was diagnosed as chondroid syringoma, but had gradually regrown. The recurrent lesion was treated by surgical re-excision. Histopathological examination was again consistent with chondroid syringoma, and showed the following: 1) a chondroid matrix, 2) tubuloalveolar structures lined by a double epithelium, 3) ductal structures lined by a single epithelium, 4) nests of polygonal cells, and 5) the presence of keratinous cysts. Chondroid syringoma is a rare mixed tumor of the skin that was first described by Hirsch and Helwig. Characteristically, it is composed of a proliferation of epithelial cells set in a myxoid and chondroid matrix. Although chondroid syringomas are predominantly benign, malignant forms have been reported.
Wednesday, August 18, 2010
Dermatopathology Quiz - Case Index :
Case 41 = Fibrous Papule of the Face (Fibrous Papule of the Nose)
Case 42 = Lupus Panniculitis (Lupus Profundus)
Case 43 =Subcutaneous Panniculitis-like T-Cell Lymphoma
Case 44 = Necrobiotic Xanthogranuloma
Case 45 = Lymphomatoid Papulosis
Case 46 = Hailey-Hailey Disease
Case 47 =Porokeratosis of Mibelli
Case 48 = Cutaneous Leiomyoma (Piloleiomyoma)
Case 49 = Mycobacterium Marinum Infection (Fish Tank Granuloma ; Swimming Pool Granuloma)
Case 50 = Cutaneous Herpes Simplex Infection
Case 51 = Prurigo Nodularis
Case 52 = Acquired Tufted Angioma
Case 53 = Merkel Cell Carcinoma
Case 54 = Ichthyosis Vulgaris
Case 55 = Discoid Lupus Erythematosus
Case 56 = Lichen Planus
Case 57 = Erythema Multiforme
Case 58 = Fixed Drug Eruption
Case 59 = Pigmented Spindle Cell Nevus of Reed.
Case 60 = Spitz Nevus
Monday, August 16, 2010
Targetoid Hemosiderotic Hemangioma
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Hobnail hemangiomas (targetoid hemosiderotic hemangiomas) are true lymphangiomas.J Cutan Pathol.2004 May;31(5):362-7.
BACKGROUND: Hobnail hemangioma (targetoid hemosiderotic hemangioma) is a small benign vascular tumor of the superficial and mid-dermis. In contrast to its well-characterized histology, it has been unclear whether this tumor arises from blood vessel endothelial cells (BECs) or lymphatic vessel endothelial cells (LECs).
METHODS: We analyzed 10 hobnail hemangiomas by immunohistochemistry, using the recently described lymphatic endothelial cell marker, D2-40. For comparison, CD31, CD34, and alpha-smooth muscle actin expression were studied in consecutive sections of the paraffin-embedded tissues.
RESULTS: In all analyzed vessels, D2-40 labeled exclusively LECs, whereas BECs were consistently negative. In contrast to capillary BECs, either neighboring the tumors or intermingled, neoplastic endothelial cells of all 10 hobnail hemangiomas were strongly labeled by D2-40.
CONCLUSIONS: The results suggest a lymphatic origin for hobnail hemangiomas. This view is further supported by the CD34 negativity of endothelial cells and the lack of actin-labeled pericytes in hobnail hemangiomas, both characteristic of lymphatic vessels. Moreover, our analysis revealed that microshunts between neoplastic lymphatic vascular channels and small blood vessels occur, explaining some features of hobnail hemangiomas, such as aneurysmatic microstructures, erythrocytes within and beneath neoplastic vascular spaces, inflammatory changes, scarring, and interstitial hemosiderin deposits.
Hobnail hemangioma ("targetoid hemosiderotic hemangioma"): clinicopathologic and immunohistochemical analysis of 62 cases. J Cutan Pathol. 1999 Jul;26(6):279-86.
Hobnail hemangioma, also known as "targetoid hemosiderotic hemangioma", represents a distinctive, benign vascular tumor, characterized histologically by a biphasic growth pattern of dilated vascular structures in the superficial dermis lined by prominent hobnail endothelial cells, and collagen dissecting, rather narrow neoplastic vessels in deeper parts of the lesion. We analyzed the clinicopathologic and immunohistochemical features in a series of 62 cases. Patient age range was 6-72 years (median: 32 years); 34 patients were male and 25 female. Clinically, a broad variation of diagnoses ranging from hemangioma to dermal melanocytic nevus and fibrous histiocytoma was suggested. Nineteen tumors arose in the lower and 13 in the upper extremities, 12 on the back, 8 in the buttock and hip region, and one case on the chest wall. Follow-up information on 35 patients (range from 1 to 4 years; mean: 1.5 years) revealed no local recurrence nor systemic metastasis. All neoplasms were located in the dermis and showed a broad morphologic spectrum in dependence of the age of the lesions. In addition to lesions resembling cavernous lymphangioma or lymphangioma circumscriptum, neoplasms were seen with morphologic features reminiscent to retiform hemangioendothelioma, progressive lymphangioma and so-called Dabska's tumor. Immunohistochemistry performed in 28 cases showed positive staining of tumor cells for CD31 in all cases tested, whereas only 3 out of 28 cases stained completely positive for CD34. In addition 4 out of 8 cases stained positively for vascular endothelial growth factor receptor-3 (VEGFR-3). Neoplastic endothelial cells were surrounded by actin-positive pericytes in only 7 out of 27 cases tested. Hobnail hemangioma occurs more frequently in male patients and arises commonly in the extremities and the trunk. Histologic and immunohistochemcial features suggest a lymphatic line of differentiation for this distinctive vascular neoplasm.
Targetoid haemosiderotic haemangioma: dermoscopic monitoring of three cases and review of the literature.Clin Exp Dermatol.2005 Nov;30(6):672-6.
Targetoid haemosiderotic haemangioma represents a new, rarely reported, distinctive, benign vascular tumour, characterized histopathologically by a biphasic growth pattern of dilated vascular structures in the superficial dermis lined by prominent hobnail endothelial cells and collagen dissecting, rather narrow neoplastic vessels in deeper parts of the lesion. In the initial stage, the lesion is seen as a small purple or violaceous papule, 2--3 mm in diameter. Over time, the ecchymotic ring expands peripherally until it disappears spontaneously. In the later stages, however, the central papule remains as a slightly raised dermal lesion with a purple to brownish discolouration. We report three cases whose repetitive cyclic morphological changes of targetoid haemosiderotic haemangiomas were monitored dermoscopically at 3-month follow-ups. Histopathological examination of each lesion identified the features of targetoid haemosiderotic haemangioma. To the best of our knowledge, our three cases are the first reported in the literature of targetoid haemosiderotic haemangiomas that were regularly monitored by dermoscopic examinations, enabling development of the different stages of the same lesion to be followed.
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Visit: Pathology of Spitz Nevus
The spitz nevus: review and update.Clin Plast Surg.2010 Jan;37(1):21-33.
The Spitz nevus is a relatively common skin lesion in children and is less commonly seen in adults. The lesion is defined by the presence of distinctive-appearing spindle or epithelioid cells on light microscopy in a recognizable nevus-like pattern. Spitz lesions share features with melanoma on light microscopic examination. When Spitz features are atypical or typical features are absent, distinction from melanoma can be difficult. A spectrum of pathology of Spitz lesions can be found from lesions that are benign and typical to lesions that are atypical with melanoma-like features and frank melanoma. There is significant interobserver variation in interpretation of Spitz lesions. The lack of uniformly applied criteria for distinction of light microscopic grades and the confusion in diagnostic terminology demonstrate the difficulty in the pathologic interpretation of these lesions. Exciting progress has been made recently in ancillary testing that will likely be helpful in determining in more detail the biologic nature of these lesions, in better differentiating the benign Spitz lesions from malignant lesions, and in eventually improving treatment recommendations.
Pediatric atypical spitzoid neoplasms: a review with emphasis on 'red' ('spitz') tumors and 'blue' ('blitz') tumors. Dermatology.2010;220(4):306-10. Epub 2010 May 6.
BACKGROUND: The diagnosis of pediatric atypical Spitz nevus/tumors (pASNT) is an emerging challenge in clinical dermatology and dermatopathology.
OBJECTIVE AND METHODS: We review the main clinicopathologic issues raised by pASNT and describe 2 examples of different clinicopathologic subsets of lesions.
RESULTS: While Spitz/Reed nevi are commonly small- to medium-sized, tan to black plaques, pASNT are large and nodular, either 'red' (dotted and/or polymorphous vascular pattern on dermoscopy; spindle and/or epithelioid tumors on histopathology: Spitz tumors, sensu strictiori) or 'blue' (homogeneous blue color on dermoscopy; intimate admixture of epithelioid cells and heavily pigmented dendritic cells on histopathology: Blitz tumors or pigmented epithelioid melanocytomas).
CONCLUSIONS: Different clinicopathologic settings of pASNT probably exist. Dermoscopy can aid in their recognition and classification.
Spitz nevus in a Hispanic population: a clinicopathological study of 130 cases.Am J Dermatopathol.2010 May;32(3):267-75.
Spitz nevus is an uncommon melanocytic nevus distinctive by its epithelioid and spindled melanocytes. Many studies have attempted to characterize Spitz nevus, but none of them in a Hispanic population. Our aim is to characterize the clinical and histopathological presentation of the Spitz nevus in a Hispanic population. A retrospective study was carried out from our files that included those cases histopathologically diagnosed as Spitz nevus. A blinded examination was performed to evaluate the histopathological characteristics of 130 lesions. The demographics of the patients, the anatomic location, and the accuracy of the clinical diagnosis were analyzed. Eighty-one females and 49 males (ratio of 1.7:1) were included in the study. The mean age was 18.8 years. Overall, the most common location was the lower extremities (41%), followed by the upper extremities (27%), trunk (16%), and head and neck (16%). The nevi followed a similar anatomic distribution in females and males. The lesions were clinically diagnosed with accuracy in 20% of the cases and characterized as a pigmented papule in 42% of the cases. Upon histopathological evaluation, most nevi exhibited symmetry (84%), were well circumscribed (91%), and exhibited epidermal hyperplasia (69%). The junctional type was seen in 42% of the cases, the compound type in 38%, and the dermal type in 20%. Sixty-eight percent of nevi were mostly composed of epithelioid melanocytes, the spindled-shaped melanocytes predominated in 17% of cases, and 12% were composed of both epithelioid and spindled-shaped melanocytes. Multinucleated melanocytes were seen in 7% of nevi, mostly in the epithelioid Spitz nevus (67%). Abundant melanin was observed in 51 cases, from which the most common variant was the classic Spitz nevi. The typical dull eosinophilic globules (Kamino bodies) were observed in a minority of the cases (11%), mostly in the classic Spitz nevus. The most common variant was the classic Spitz nevus (65%), followed by the dermal Spitz nevus (15%). In conclusion, Spitz nevus in a Hispanic population most commonly presents as a pigmented papule on the lower extremities irrespective of sex and age. It is characterized by a melanocytic proliferation most commonly composed of nested epithelioid melanocytes in a junctional or compound arrangement, with the presence of abundant melanin.
Spitz nevus: a clinicopathological study of 349 cases. Am J Dermatopathol.2009 Apr;31(2):107-16.
Spitz nevus is an infrequent, usually acquired melanocytic nevus composed of epithelioid and/or spindle melanocytes that can occasionally be confused with melanoma. Currently, there are no immunohistochemical markers or molecular biology techniques that can be used to make an entirely safe diagnosis of Spitz nevus or melanoma in problematic cases. A retrospective study has been carried out that included all the cases diagnosed as Spitz nevus from our files. Follow-up information of the patients was unavailable. Three hundred forty-nine cases of unequivocal Spitz nevi were included, and their clinical and histopathological parameters were reviewed. One hundred and forty patients (40%) were 15 years old or younger, with a male to female ratio of 1:1. In patients older than 15 years, there was an evident predominance of women, with a male to female ratio of around 1:3. Spitz nevus was most commonly located on the lower extremities, followed by the trunk in both children and adults. Despite the fact that the head and neck were the third most common location in children, it was a much more frequent location in children than in adults. The constitution by epithelioid and/or spindled cells was the only histopathological finding present in 100% of cases. The other pathological findings studied were, from more to less frequent: maturation (72%), inflammatory infiltrate (70%), epidermal hyperplasia (66%), melanin (50%), telangiectasias (40%), Kamino bodies (34%), desmoplastic stroma (26%), mitosis (23%), pagetoid extension (13%), and hyalinization of the stroma (8%). Hyalinization was the only histopathological parameter that was statistically more frequent in adults than in children.
Spitz nevus with an uncertain malignant potential.Rom J Morphol Embryol. 2009;50(2):275-82.
We present the case of 10-year-old girl who have had from birth a plane tumor, of tan color, 3-4 mm of diameter, localized on the face on the cutaneous part of the superior lip. This tumor has been stabile until 8-year-old. Then, after repeated sunlight exposures, the lesion has become more stark, hemispheric in shape, has increased in size becoming about 5-6 mm, with irregular borders, and after an accidental traumatism it began to bleed. We have performed the electroexcision of the lesion for diagnostic and therapeutic purpose. The histopathologic exam distinguished typical images of Spitz nevus on some of the histological sections but also of melanocytary tumor with uncertain malignant potential on the others where atypical mitoses localized in the deeper component of the tumor are being noticed. The immunohistochemical assessment of the tumoral cells showed positivity for the melanocytic markers HMB45 and Melan A, within junctional intraepidermic nevic cells and in the nevic cells from superficial dermis, and also for CD44 protein (belonging to the adhesion molecules family). However, cyclin D1 was positive in rare nevic cells, and the proliferation rate of the tumor was small, with a proliferation index for Ki67 lesser than 5%. The correlation between histopathological and immunohistochemical data conducive to final diagnosis of Spitz nevus with uncertain malignant potential. The clinical evolution confirmed the histopathological diagnosis by the fact that the patient did not presented clinical signs of local recurrences or metastasis at three years after the excision of the tumor.
Pigmented Spindle Cell Nevus of Reed.
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Visit: Pigmented Spindle Cell Nevus (Reed Nevus)
Hypopigmented Reed nevus.J Cutan Pathol. 2008 Oct;35 Suppl 1:87-9. Epub 2008 Jun 28.
Reed nevus, also named pigmented spindle cell nevus, is a peculiar melanocytic nevus, now regarded as a variant of Spitz nevus by the majority of authors. It is characterized by spindle-shaped melanocytes disposed in nests located in epidermis and papillary dermis. It is usually heavily pigmented, and many melanophages may also be present. Hypopigmented Reed nevus shows all the typical features of conventional pigmented spindle cell nevus, but it does not contain abundant melanin. This variant of Reed nevus is poorly described in literature, so we report five cases of hypopigmented Reed nevus and discuss its clinical and histopathological features.
Epithelioid and hyperpigmented melanocytic tumors. An overview. Pathologe. 2007 Nov;28(6):411-21.
Spindle cell and epithelioid cell differentiation occur in both benign and malignant hyperpigmented melanocytic lesions. Reed nevus is characterized by compact, sharply circumscribed junctional cellular nests composed of slender hyperpigmented melanocytes shaped like spindle cells. Deep penetrating nevus is characterized by a diffuse dermal proliferation composed of small nests and fascicles of pale ovoid and epithelioid melanocytes. Cellular blue nevi often have a characteristic hourglass or dumbbell shape, with sharply circumscribed elongated nests and fascicles of pale, densely layered ovoid melanocytes and adjacent melanophages. Epithelioid blue nevus is characterized by large epithelioid melanocytes with abundant cytoplasm and melanin often concentrated to some degree in the cell membrane. Animal-type melanoma is a particularly hyperpigmented variant of melanoma in which large melanophages predominate and there are varying proportions of melamin-rich spindle-shaped and large atypical epithelioid melanocytes. Morphologically, pigmented epithelioid melanocytoma combines characteristics of both animal-type melanoma and pigmented epithelioid nevus. Malignant melanoma may occur in conjunction with a preexistent blue nevus. Malignant blue nevus is now regarded as a malignant melanoma mimicking a blue nevus in structure and pattern. It is therefore of paramount importance to view multiple mitoses within a cellular blue nevus-like proliferation as an alarm signal as they are usually indicators of a malignant melanoma.
Melanocytic nevi simulant of melanoma with medicolegal relevance.Virchows Arch. 2007 Sep;451(3):623-47. Epub 2007 Jul 26.
A group of melanocytic benign nevi are prone to be misdiagnosed as nodular or superficial spreading melanoma. This review illustrates the most frequent forms of these nevi in direct comparison with their malignant morphologic counterparts. The nevi are: hyper-cellular form of common nevus to be distinguished from nevoid melanoma, Spitz nevus (vs spitzoid melanoma), Reed nevus (vs melanoma with features of Reed nevus), cellular atypical blue nevus (vs melanoma on blue nevus), acral nevus (vs acral melanoma), Clark dysplastic nevus (vs superficial spreading melanoma), desmoplastic nevi (vs desmoplastic melanoma), benign proliferative nodules in congenital nevi (vs melanoma on congenital nevi), epithelioid blue nevus (vs animal type melanoma) and regressed nevus (vs regressed melanoma). For each single 'pair' of morphological look-alikes, a specific set of morphological, immunohistochemical and genetic criteria is provided.
Pigmented spindle cell nevus: a clinicopathologic analysis of ninety-five cases. J Am Acad Dermatol.1993 Apr;28(4):565-71.
BACKGROUND: Pigmented spindle cell nevus (PSCN) is often interpreted as a Spitz nevus or misdiagnosed as malignant melanoma.
OBJECTIVE: The purpose of this study was to analyze the clinical and histologic features and to determine the biologic behavior of 95 cases of PSCN.
METHODS: We reviewed clinical data, follow-up information, and microscopic features of all 95 cases of PSCN.
RESULTS: PSCNs are dark brown to black, 3 to 6 mm in diameter, and occur most commonly on the extremities (75%) and back (16%) with a predilection for the legs. These lesions are more common in women in the third decade of life. Microscopically, PSCNs are characterized by uniform, spindle-shaped, pigmented melanocytes. Although some histologic features overlap with those in spindle and epithelioid cell nevus, PSCN is a separate entity. In addition, PSCN must be differentiated from malignant melanoma. Fifty-seven patients (60%) observed for an average of 6 years did not develop local recurrence or metastasis.
CONCLUSION: PSCN is a distinctive, acquired, benign melanocytic lesion, that should not be confused with spindle and epithelioid cell nevus or malignant melanoma. Complete excision is recommended for treatment.
Pigmented spindle cell nevus. Clinical and histologic review of 90 cases. Am J Surg Pathol.1984 Sep;8(9):645-53.
A clinical and histologic review of 90 patients with melanocytic lesions termed pigmented spindle cell nevi (PSCN) is reported. The lesions are small in surface diameter, sharply confined both clinically and histologically, and often occur on the proximal extremities of young adults. They are generally of recent onset, moderately to heavily pigmented, and made up of nests of spindled cells confined to the epidermis and papillary dermis. There were 30 male and 60 female patients. Their average age was 25.3 years (ranging from 2.5 to 56 years). Lesions were located on the extremities in 61 cases (67%). Follow-up was possible in 38 cases seen more than 6 months after histologic diagnosis and ranged up to 40 months (average 14 months). No local recurrence or distant spread was found. The importance of recognizing this lesion lies in differentiating it from malignant melanoma. Conservative but complete excision has resulted in no recorded instances of local recurrence or distant spread.
The pigmented spindle cell tumor of Reed: an underdiagnosed lesion.Semin Diagn Pathol.1987 Feb;4(1):75-87.
The pigmented spindle cell tumor is a distinct benign melanocytic lesion with characteristic clinical and histopathologic features. Until recently, it has been poorly documented in the literature and is frequently misdiagnosed as malignant melanoma. On the basis of 40 personal cases of pigmented spindle cell tumor, the clinical and pathologic features of the lesion and its differential diagnosis will be discussed.
Fixed Drug Eruption
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Clinical resemblance of widespread bullous fixed drug eruption to Stevens-Johnson syndrome or toxic epidermal necrolysis: report of two cases.J Formos Med Assoc. 2002 Aug;101(8):572-6.
Widespread bullous fixed drug eruption (FDE) is the most severe form of FDE and may be mistaken clinically for Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN). We report two cases of generalized bullous drug eruption with extensive epidermal necrosis and detachment mimicking SJS/TEN overlap and TEN, respectively. The first patient, a 78-year-old man, developed SJS/TEN-like eruption with widespread dusky red patches and denuded areas shortly after taking multiple nonsteroidal antiinflammatory drugs (NSAIDs). Histopathology showed vacuolar interface dermatitis with numerous necrotic keratinocytes and a superficial and deep perivascular infiltrate containing lymphocytes, eosinophils, neutrophils and melanophages. These findings are consistent with FDE. The second patient, a 61-year-old woman, had three episodes of near-total body epidermal detachment shortly after taking NSAIDs. TEN was diagnosed clinically in all three episodes without pathologic confirmation. FDE was suspected due to lack of involvement of two mucosal sites and uneventful recovery. These cases highlight the importance of considering severe bullous FDE in the differential diagnosis of SJS and TEN, and the necessity of skin biopsy in such cases.Fixed drug eruption: pathogenesis and diagnostic tests. Curr Opin Allergy Clin Immunol.2009 Aug;9(4):316-21.
PURPOSE OF REVIEW: Fixed drug eruption is a simplified disease model for elucidating the mechanism(s) of how skin inflammation is induced by skin-resident T cells. In this review, we focus on how the presence of intraepidermal CD8+T cells resident in the fixed drug eruption lesions can provide exciting new clues to our understanding of pathomechanisms of inflammatory skin diseases.
RECENT FINDINGS: Intraepidermal CD8+T cells with an effector-memory phenotype resident in fixed drug eruption lesions have a major contributing role in the development of localized tissue damage. Activation of these CD8+T cells is sufficient for triggering the lesion, however, but not sufficient to cause extensive tissue damage observed in the fully evolved lesions; additional recruitment of CD4+ and CD8+T cells to a specific tissue site would also contribute to the late stage of lesion development. The influx of regulatory T cells into the epidermis observed in fully evolved lesions would serve to limit harmful immune reactions. Consistent with this, positive patch test reactions are only observed at the site of previous lesions harboring significant numbers of intraepidermal CD8+T cells.
SUMMARY: Intraepidermal CD8+T cells may represent double-edged swords of the skin immune system with protective and destructive capacity.
Histological phases of Bactrim-induced fixed drug eruption. The report of one case.Am J Dermatopathol. 1987 Dec;9(6):528-32.
A case is described of a patient with Bactrim-induced fixed drug eruption (FDE). Histological studies were performed at 1 day and 5 days after the drug exposure. While the 5-day-old lesion showed changes classically recognized as FDE, the 1-day-old lesion showed changes typical of a hypersensitivity response: diffuse spongiosis, dermal edema and hemorrhage, neutrophilic polymorphonuclear leukocyte abscess formations, and large numbers of eosinophils. This report underscores the dynamic cellular changes that occur in the evolving FDE lesion.
Pigmentary incontinence in fixed drug eruptions. Histologic and electron microscopic findings.J Am Acad Dermatol.1983 Apr;8(4):525-32.
Pigmentary incontinence is a phenomenon observed in some inflammatory skin disorders. Clinically it may be seen as a slate-colored pigmentation. Histologically it is seen as an accumulation of melanin in the upper dermis. The possible mechanism for development of pigmentary incontinence is discussed based on a review of the literature and electron microscopic studies of fixed drug eruption.
Sunday, August 15, 2010
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Lichenoid histopathologic changes in patients with clinical diagnoses of exfoliative dermatitis. Am J Dermatopathol.1991 Aug;13(4):358-64.
Among 30 patients who received a clinical diagnosis of exfoliative dermatitis and were biopsied between 1982 and 1990, nine showed microscopic features of lichenoid dermatitis. Clinical information was available in eight of these cases. Possible etiologic factors included lymphoma, herpes simplex infection, connective tissue disease, and (in five cases) reactions to drugs. In each instance, microscopic features included a superficial perivascular lymphocytic infiltrate involving the dermal-epidermal interface, vacuolar alteration of the basilar layer, and individually necrotic keratinocytes at all levels of the epidermis. Such microscopic changes are not usually described in connection with exfoliative dermatitis, with the possible exception of those cases related to lichen planus or lupus erythematosus. Disseminated lichenoid drug eruption is one possible interpretation of the drug-induced cases. Erythema multiforme is another condition that has similar microscopic features and has been associated with drugs (many of which also cause exfoliative dermatitis), infectious agents, neoplasms, and connective tissue diseases. Lichenoid dermatitis can become generalized and clinically mimic and exfoliative dermatitis. Many, but not all, of these eruptions may be triggered by drugs.
[Erythema multiforme. A heterogeneous pathologic phenotype]Minerva Stomatol. 1999 May;48(5):217-26.
The term Erythema Multiforme (EM) include actually a wide range of clinical expressions, from exclusive oral erosions (Oral EM) to mucocutaneous lesions (EM Minor), sometimes with severe involvement of multiple mucosal membrane (EM major, Stevens-Johnson syndrome [SJS]) or with involvement of a large area of the total body surface (toxic epidermal necrolysis [TEN]). However, this terminology is not worldwide accepted and often the various clinical categories show some overlapping features. Among the great number of suspected etiological factors, herpes simplex virus is involved in many cases of EM minor whereas SJS and TEN are caused in 80% of cases by systemic drugs, mainly by anticonvulsivants, sulfonamides, nonsteroidal anti-inflammatory drugs and antibiotics. Several oral EM seem idiopathic, but data on this topic are very few. There is no specific or consistent microscopic and immunopathologic pattern of EM and the diagnosis should be done by excluding other similar diseases. The treatment include the use of antivirals for EM minor, mainly if recurrent, and of immunosuppressants (especially systemic corticosteroids) for SJS. TEN patients require adequate supportive care and often they have to be treated in emergency departments. Finally, patients with exclusive oral lesions may be treated with both topical and systemical corticosteroids.
Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study.Arch Dermatol.2002 Aug;138(8):1019-24.
BACKGROUND: It was proposed that Stevens-Johnson syndrome and toxic epidermal necrolysis differed from erythema multiforme majus by the pattern and localization of skin lesions.
OBJECTIVE: To evaluate the validity of this clinical separation.
DESIGN: Case-control study.
SETTINGS: Active survey from 1989 to 1995 of 1800 hospital departments in Europe.
PATIENTS: A total of 552 patients and 1720 control subjects.
METHODS: Cases were sorted into 5 groups (erythema multiforme majus, Stevens-Johnson syndrome, Stevens-Johnson syndrome-toxic epidermal necrolysis overlap, toxic epidermal necrolysis, and unclassified erythema multiforme majus or Stevens-Johnson syndrome) by experts blinded as to exposure to drugs and other factors. Etiologic fractions for herpes and drugs obtained from case-control analyses were compared between these groups.
RESULTS: Erythema multiforme majus significantly differed from Stevens-Johnson syndrome, overlap, and toxic epidermal necrolysis by occurrence in younger males, frequent recurrences, less fever, milder mucosal lesions, and lack of association with collagen vascular diseases, human immunodeficiency virus infection, or cancer. Recent or recurrent herpes was the principal risk factor for erythema multiforme majus (etiologic fractions of 29% and 17%, respectively) and had a role in Stevens-Johnson syndrome (etiologic fractions of 6% and 10%) but not in overlap cases or toxic epidermal necrolysis. Drugs had higher etiologic fractions for Stevens-Johnson syndrome, overlap, or toxic epidermal necrolysis (64%-66%) than for erythema multiforme majus (18%). Unclassified cases mostly behaved clinically like erythema multiforme.
CONCLUSIONS: This large prospective study confirmed that erythema multiforme majus differs from Stevens-Johnson syndrome and toxic epidermal necrolysis not only in severity but also in several demographic characteristics and causes.
Analysis of the acute ophthalmic manifestations of the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum.Ophthalmology.1995 Nov;102(11):1669-76.
PURPOSE: To evaluate the epidemiology, possible etiologic factors, complications encountered, and treatment administered to a group of patients with ocular involvement in the erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum who were seen at two large tertiary referral centers over a 34-year period.
METHODS: Hospital records from 1960 to 1994 at the Massachusetts General Hospital and Shriners Hospital for Crippled Children were reviewed for patients with erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. Only patients fulfilling specific clinical diagnostic criteria and those who received a diagnosis by a dermatologist were included in the review.
RESULTS: A total of 366 patients with erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis were identified. Drugs were the most commonly identified etiologic factor in all three conditions: sulfonamides were the most frequently identified agents. Eighty-nine patients (24%) had ocular manifestations at the time of their acute hospital stay. Ocular involvement was seen in 9% of patients with erythema multiforme, in 69% with Stevens-Johnson syndrome, and in 50% with toxic epidermal necrolysis. The ocular problems were more severe in patients with both Stevens-Johnson syndrome and toxic epidermal necrolysis. There was no significant difference between the number of patients who were treated with systemic steroids and those who were not (P = 0.42).
CONCLUSIONS: The erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease spectrum remains an important cause of severe visual loss in a significant number of patients. Systemic steroids used during the acute phase of the disease appear to have no effect on the development of ocular manifestations. Studies on the acute immunopathogenic mechanisms occurring in these disease are warranted if more effective therapies are to be found.
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Lichen planus and lichenoid reactions of the oral mucosa.Dermatol Ther. 2010 May-Jun;23(3):251-67.
Oral lichenoid reactions represent a common end point in response to extrinsic agents (drugs, allergens), altered self-antigens, or superantigens. Oral lichen planus, a common and under-recognized inflammatory disorder, shares many clinical and histopathological features with oral lichenoid drug reaction and oral lichenoid contact reaction. Clinical presentation can vary from asymptomatic white reticular striae to painful erythema and erosions. Cutaneous and additional mucosal involvement is common. Delay in diagnosis of extraoral mucocutaneous lichen planus (LP) results in conjunctival scarring; vaginal stenosis; vulvar destruction; and stricture of the esophagus, urethra, and external auditory meatus. Although the etiology of LP is idiopathic, oral lichenoid reactions may be caused by medications or exogenous agents such as cinnamates and other flavorings. The clinical features, evaluation, and management of these oral lichenoid reactions are discussed.
Lichen planus in children.Indian J Dermatol Venereol Leprol.2010 Jul-Aug;76(4):366-72.
Lichen planus in children is considered to be rare overall, though it does not appear to be so in Indian subcontinent. Most of the large studies on lichen planus in children have been undertaken in India. We review here the epidemiology, pathogenesis, clinical features, diagnosis, management and prognosis pertaining to lichen planus in children with emphasis on studies published from India.
Lichen planus. Curr Opin Dent.1991 Dec;1(6):769-72.
During the past year, few articles have been published regarding the various aspects of oral lichen planus. The work reported dealt with a variety of aspects including patient profile, immunopathogenesis, and treatment. The papers served to confirm previous concepts of an immunologic etiology, the demographic consensus on patient profiles, and the use of topical or systemic corticosteroids as the most effective treatment approach. This review also summarizes some highlights of previous studies of oral lichen planus prior to 1990 and summarizes a current unpublished prospective study reflecting the findings in a large number of patients with oral lichen planus who have been followed for a long period of time.
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Histologic features of cutaneous lupus erythematosus.Autoimmun Rev.2009 May;8(6):467-73. Epub 2009 Jan 20
Histologic examination of lesions plays a key role in the diagnostics of cutaneous lupus erythematosus (LE). LE has a broad spectrum of histopathological signs, which are related to the stages of the lesions. In addition to the main subtypes of LE, we report on special manifestations like Rowell's-syndrome and Chilblain LE, and give an account of Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis), which may be associated with systemic LE. Furthermore the most considerable histopathologic differential diagnoses are discussed.
The different faces of cutaneous lupus erythematosus. G Ital Dermatol Venereol.2009 Apr;144(2):135-47.
Lupus erythematosus is a chronic and inflammatory multiorgan disease with variable clinical appearance and variable course. Most patients with systemic lupus erythematosus show cutaneous manifestations and conversely, all forms of cutaneous LE may change into a systemic involvement. Specific lesions of cutaneous LE are classified in different subtypes of acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), chronic cutaneous lupus erythematosus (CDLE) and intermittent cutaneous lupus erythematosus (ICLE) according to clinical, histological and immunoserological parameters. Regular laboratory tests are important to monitor the activity and course of the disease or side effects of the therapy. In case of clinical or laboratory dysfunctions of internal organs, additional technical investigations are necessary. Histology is needed to support clinical diagnosis. A large number of drugs are able to induce SCLE, e.g. hydrochlorothiazide, terbinafine, or angiotensin-converting enzyme inhibitors. Drug-induced SCLE can be differentiated by possible complementary immunoserological parameters. Neonatal lupus can be induced by transplacental transmission of maternal anti-Ro(SS-A) and anti-La(SS-B)-antibodies. Children with neonatal lupus might suffer from congenital atrioventricular block. Their mothers may suffer from active LE, but can be clinically healthy as well. As a consequence, pregnancies at risk should be monitored in short intervals by serial echocardiographic interventions. Protection against UV light is recommended for all types of CLE. There are some topical and many systemic treatment options e.g. topical and systemic glucocorticosteroids, antimalarial drugs, dapsone, azathioprine, or mycophenolate mofetil with different response to skin or organ involvement.
Cutaneous lupus erythematosus: issues in diagnosis and treatment.Am J Clin Dermatol. 2009;10(6):365-81. doi: 10.2165/11310780-000000000-00000.
Cutaneous lupus erythematosus (LE) may present in a variety of clinical forms. Three recognized subtypes of cutaneous LE are acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), and chronic cutaneous LE (CCLE). ACLE may be localized (most often as a malar or 'butterfly' rash) or generalized. Multisystem involvement as a component of systemic LE (SLE) is common, with prominent musculoskeletal symptoms. SCLE is highly photosensitive, with predominant distribution on the upper back, shoulders, neck, and anterior chest. SCLE is frequently associated with positive anti-Ro antibodies and may be induced by a variety of medications. Classic discoid LE is the most common form of CCLE, with indurated scaly plaques on the scalp, face, and ears, with characteristic scarring and pigmentary change. Less common forms of CCLE include hyperkeratotic LE, lupus tumidus, lupus profundus, and chilblain lupus. Common cutaneous disease associated with, but not specific for, LE includes vasculitis, livedo reticularis, alopecia, digital manifestations such as periungual telangiectasia and Raynaud phenomenon, photosensitivity, and bullous lesions. The clinical presentation of each of these forms, their diagnosis, and the inter-relationships between cutaneous LE and SLE are discussed. Common systemic findings in SLE are reviewed, as are diagnostic strategies, including histopathology, immunopathology, serology, and other laboratory findings. Treatments for cutaneous LE initially include preventive (e.g. photoprotective) strategies and topical therapies (corticosteroids and topical calcineurin inhibitors). For skin disease not controlled with these interventions, oral antimalarial agents (most commonly hydroxychloroquine) are often beneficial. Additional systemic therapies may be subdivided into conventional treatments (including corticosteroids, methotrexate, thalidomide, retinoids, dapsone, and azathioprine) and newer immunomodulatory therapies (including efalizumab, anti-tumor necrosis factor agents, intravenous immunoglobulin, and rituximab). We review evidence for the use of these medications in the treatment of cutaneous LE.
Classification of lupus erythematosus based upon cutaneous manifestations. Dermatological, systemic and laboratory findings in 191 patients.Dermatology. 1995;190(4):277-83.
BACKGROUND: Lupus erythematosus (LE) is a multi-organ-system disease, the characteristics of which are reflected in the 1982 American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). From a dermatological point of view, only the presence of LE-specific histopathology is necessary and sufficient for the diagnosis of LE. The association between the type of LE-specific skin lesion and the severity of extracutaneous manifestations of LE has not yet been investigated systematically.
OBJECTIVE: The aim of this study was to evaluate, according to the type of LE skin lesions, the prevalence of the 1982 criteria for SLE.
METHODS: We selected 191 patients whose skin lesions were histologically diagnosed as LE specific. Patients were classified on the basis of skin disease, and their clinical and laboratory data were analyzed.
RESULTS: Of 191 patients, 130 (68%) exhibited only one type of LE-specific skin lesion (monomorphic), 55 (29%) had two types (bimorphic) and the remaining 6 (3%) displayed three types (trimorphic). Nineteen of 22 (86%) patients who presented discoid lupus skin lesions above the neck without other eruptions were classified in the cutaneous-limited LE spectrum. Of 116 patients with acute lupus skin lesions (malar rash), 83 (72%) clearly fulfilled the 1982 ARA criteria for SLE. In skin lesions of LE profundus, chilblain lupus, subacute lupus (annular-polycyclic erythema and the papulosquamous variant), there were no significant correlations between the type of eruption and the severity of extracutaneous manifestations.
CONCLUSION: Patients with acute lupus skin lesions could usually be classified as suffering from SLE, whereas monomorphic patients with localized discoid lesions rarely exhibited extracutaneous manifestations. This tendency was less distinct in bimorphic patients. Almost all patients with subacute skin lesions were bimorphic or trimorphic, which might be due to genetic or racial differences between Japanese and other populations.
Markers in cutaneous lupus erythematosus indicating systemic involvement. A multicenter study on 296 patients.Acta Derm Venereol.1997 Jul;77(4):305-8.
Lupus erythematosus (LE) is an autoimmune disorder, involving the skin and/or other internal organs. As cutaneous variants, chronic discoid LE (CDLE) and subacute cutaneous LE (SCLE) usually have a better prognosis, however, involvement of internal organs with transition into systemic disease may occur. The aim of this study was to assess the significance of some clinical and laboratory criteria that could serve as markers for early recognition of systemic involvement in cutaneous LE. Three hundred and seventy-nine patients with LE, seen in five cooperating Departments of Dermatology during the years 1989-1994, were documented by electronic data processing according to a common protocol. Two hundred and forty-five of these patients had cutaneous LE (CDLE or SCLE), and 51 had systemic LE (SLE) and were included in this study. Forty-nine patients with either CDLE/SCLE or SLE were not evaluated because of incomplete documentation; also, 34 patients suffered from other LE subsets and were likewise excluded from the evaluation. Multivariate statistical analysis was used to assess the value of seven selected variables for distinguishing between the CDLE/SCLE and SLE groups: ESR, titers of antinuclear antibodies, anti-dsDNA-antibodies, photosensitivity, presence of arthralgias, recurrent headaches and signs of nephropathy. Univariate and multivariate analysis of the obtained data showed that signs of nephropathy (proteinuria, hematuria) was the variable with the highest statistical relevance for distinguishing between patients with cutaneous (CDLE/SCLE) and with systemic LE (SLE) in all statistical models tested, followed by the presence of arthralgias and of high ANA titers (> or =1:320). In contrast, low ANA titers as well as anti-dsDNA antibodies showed little or no statistical relevance as a criterion for distinction. It seems, therefore, that cutaneous LE patients showing signs of nephropathy, presence of arthralgias and elevated ANA titers (> or =1:320) should be carefully monitored, because they may be at risk of developing systemic LE involvement.
Wednesday, August 4, 2010
Monday, August 2, 2010
Clinical features of the nephrotic syndrome associated with ichthyosis vulgaris and analysis of related gene mutation.Zhonghua Er Ke Za Zhi.2010;48(1):44-9.
OBJECTIVE: To study clinical features of 3 children who presented with nephrotic syndrome (NS) associated with ichthyosis vulgaris (IV), and to detect relationship between NS associated with IV in patients and FLG gene or NPHS2 gene. METHOD: Clinical and kidney pathological data of the 3 patients were analyzed and progress of pathologic damage in the patient kidney was observed through repeated percutaneous renal biopsy. Using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing, the diversity of the expression of NPHS2 gene in the 3 patients were analyzed, and FLG gene in the 3 patients and parts of their family members with IV was detected. RESULT: (1) The age of the 3 patients (patient 1 was a girl and patients 2 and 3 were boys) suffering from NS was 3 years and 8 months, 2 years and 6 months, and 5 years and 3 months, respectively. The age of onset of IV was 1 year and 6 months, 10 months, and 2 years and 6 months, respectively. All the 3 patients were resistant to steroid therapy. Despite multi-immunosuppressive therapy, no clinical response was achieved. The patients were followed up for 1.5 to 4.0 years. The patients displayed continuous proteinuria, renal function was normal, but their heights were lower than other children at the same age. (2) The older brother of patient 1 died of uremia. The other patients' family members did not have kidney disease. (3) Renal histopathology showed that the patients 1 and 2 had mild mesangial proliferative glomerulonephritis (MsPGN) and the patient 3 had minimal change disease (MCD). One and a half years after the first renal biopsy, the patients 1 and 2 underwent repeated renal biopsy. Renal histopathology showed that the 2 patients' disease developed to medium MsPGN. (4) None of the 3 patients had NPHS2 gene mutation. All the three patients had R501X and 2282del4 which are the common gene mutation type of the FLG, and all the patients were heterozygote. With the detection of the FLG gene of the part of the patients of the three families, the second patient's grandfather had the R501X homozygote mutation and the others were the R501X heterozygote mutation and 2282del4 heterozygote mutation. CONCLUSION: The 3 cases of NS associated with IV had no response to steroid and multi-immunosuppressive therapy, the renal damage observed by histopathology progressed fast. The children with NS associated with IV displayed R501X heterozygote mutation and 2282del4 heterozygote mutation of FLG gene, which suggested that the absence of response to steroid and multi-immunosuppressive therapy may be related to the FLG gene.
Novel and recurrent mutations in the filaggrin gene in Chinese patients with ichthyosis vulgaris.Br J Dermatol.2010 Jul;163(1):63-9. Epub 2010 Mar 19.
BACKGROUND: Ichthyosis vulgaris (IV) is a common inherited skin disorder, and the filament aggregating protein (filaggrin) is a key protein involved in skin barrier function. Mutations in the filaggrin gene (FLG) have recently been identified as the cause of IV. However, there have been no reports of FLG mutations in mainland Chinese families with IV. OBJECTIVES: To identify FLG mutations in Chinese patients with IV. METHODS: Eleven unrelated Chinese families with IV were examined for FLG mutations with denaturing high-performance liquid chromatography prescreening and sequencing. SNaPShot was employed to obtain a high-throughput screening for the identified mutations. RESULTS: Three mutations - one novel mutation (Q1256X) and two known mutations (3321delA and E2422X) - were identified in these families. The novel mutation, Q1256X, found in a Chinese family with IV, was located in filaggrin repeat 3. Mutation 3321delA, previously found in Japanese patients, was present in eight Chinese families with IV. Mutation E2422X, previously found in a Dutch patient of Chinese origin, was present in two Chinese families with IV. Neither of the null mutations, Q1256X and E2422X, were found in 100 unrelated control cases from the Chinese population; however, the mutation ratio for 3321delA was 3% in these controls. CONCLUSIONS: Our study suggests that each population may have a unique and prevalent set of FLG mutations.
FLG mutations in ichthyosis vulgaris and atopic eczema: spectrum of mutations and population genetics.Br J Dermatol.2010 Mar;162(3):472-7. Epub 2009 Dec 2.
Filaggrin is a key protein involved in skin barrier function. Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris and have been shown to be major predisposing factors for atopic eczema (AE), initially in European populations. Subsequently, FLG mutations were identified in Japanese, Chinese, Taiwanese and Korean populations. It was demonstrated that FLG mutations are closely associated with AE in the Japanese population. Notably, the same FLG mutations identified in the European population were rarely found in Asians. These results exemplify differences in filaggrin population genetics between Europe and Asia. For mutation screening, background information needs to be obtained on prevalent FLG mutations for each geographical population. It is therefore important to establish the global population genetics maps for FLG mutations. Mutations at any site within FLG, even mutations in C-terminal imperfect filaggrin repeats, cause significant reductions in amounts of profilaggrin/filaggrin peptide in patient epidermis as the C-terminal region is essential for proper processing of profilaggrin into filaggrin. Thus, no genotype-phenotype correlation has been observed in patients with FLG mutations. A restoration of the barrier function seems a feasible and promising strategy for treatment and prevention in individuals with filaggrin deficiency.