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Importance: Controversy persists regarding the appropriate management of incompletely excised, biopsy-proven, mild and moderate dysplastic nevi (DN)., Objective: To determine long-term risk of associated melanoma in biopsied mild or moderate DN with positive histologic margins that were clinically observed vs reexcised with negative margins., Design, Setting, and Participants: Retrospective cohort study of mixed referral and community patients from an academic pigmented lesion clinic and dermatology clinics of the affiliated Veteran Affairs medical center with biopsy-confirmed DN with positive histologic margins diagnosed from May 15, 1991, to July 8, 2015, and followed up through May 30, 2016. A consecutive sample of 1473 histologically confirmed DN was identified using surgical pathology databases at the study sites; 590 cases in 498 patients met eligibility criteria., Main Outcomes and Measures: The primary outcome was the proportion of biopsied DN that progressed to histologically confirmed invasive or in situ melanoma. Secondary outcomes included local nevus recurrence and development of primary melanoma at other anatomic sites., Results: The 498 patients had a mean (range) age of 57.6 (14-93) years and 90% were male. Among 590 positive-margin DN, 191 were reexcised and 399 clinically observed without further surgery; 170 reexcised and 304 observed DN had available follow-up data, with mean (SD) follow-up of 5.5 (4.6) years. Cases in the observation group were more likely to demonstrate nevus recurrence than those that were reexcised (3.3% vs 0%; P = .02). Six of 304 (2.0%) observed DN subsequently developed melanoma at the same site, compared with 1 of 170 (0.06%) that were reexcised (P = .43). Five of 6 observed patients who developed melanoma initially underwent partial biopsy with grossly positive margins; 1 melanoma in situ evolved from an excisionally biopsied moderately dysplastic nevus 5 years later. Only 1 case of thin invasive melanoma (≤1 mm) was observed, and no deaths from melanoma arising from biopsy-proven DN occurred through the latest dermatology follow-up. New primary melanoma developed at other sites in 9.9% of excised and 9.4% of resected DN., Conclusions and Relevance: In cases of mild and moderate DN with microscopically positive margins and no concerning clinical residual lesion, observation, rather than reexcision, was a reasonable management option. Partial biopsies of pigmented lesions suspicious for melanoma may lead to delayed melanoma diagnosis and should be discouraged.

Fibrous papules present clinically as benign, asymptomatic, dome-shaped, flesh colored papules on the face. Histologically, fibrous papules are characterized by fibrous stroma with fibroblasts and dilated blood vessels. Multiple variants of fibrous papules have been reported. Although scattered multinucleated cells in fibrous papules have been well described, we report a fibrous papule with abundant multinucleated ganglion-like giant cells that were immunoreactive with CD34. Recognition of such fibrous papule variants is important to avoid misdiagnosis as potentially more worrisome and/or aggressive melanocytic, soft tissue, or neural lesions that may require more aggressive treatment. Indeed, fibrous papules do not commonly appear on the differential diagnosis for lesions with multinucleated giant cells or ganglion-like cells and consideration should be given to their inclusion in the appropriate clinical setting.

Background: Surgical resection of lentigo maligna (LM) is complicated by noncontiguous, subclinical extension and actinic melanocytic hyperplasia in sun-damaged skin of older individuals., Objective: We sought to determine the long-term effectiveness of imiquimod as primary or adjuvant therapy for LM., Methods: Patients were retrospectively identified from January 1, 2003, to December 31, 2013, with LM, early/evolving LM, and LM melanoma who had used topical imiquimod 5% cream for either primary therapy after diagnostic biopsy, or adjuvant therapy after narrow-margin surgical resection or complete clinical but not histologic resection of LM. Follow-up occurred through December 31, 2014., Results: In all, 63 cases were identified in 61 patients, mean (SD) age 71.1 (12.4) years; 58 were analyzed for local recurrence. Imiquimod was used as primary therapy in 22 of 63 (34.9%) and adjuvant therapy in 41 of 63 (65.1%) for mean duration of 11.7 (range 2-60) weeks. Fifty cases (86.2%) demonstrated clinical clearance at mean (SD) follow-up of 42.1 (27.4) months: 72.7% primary and 94.4% adjuvant at 39.7 (23.9) and 43.1 (28.9) months, respectively., Limitations: Retrospective cohort study and lack of standardized imiquimod application are limitations., Conclusion: Imiquimod cream appears to be a viable option for primary or adjuvant treatment of LM in older patients who are poor surgical candidates., (Published by Elsevier Inc.)

Chromhidrosis is a rare idiopathic disorder characterized by colored secretions most typically from the malar cheeks, axilla, or areolar regions. Histologically, chromhidrosis is notable for glandular structures with decapitation secretion indicating ectopic apocrine glands in the dermis, and the presence of lipofuscin pigments under ultraviolet fluorescence and in cytology smears. This case report describes a 26-year-old man who presented with a 2- to 3-year history of black-colored secretions on the bilateral malar cheeks, present on exertion or with squeezing of the cheeks. A 3-mm punch biopsy of the left cheek demonstrated histopathologic findings characteristic of chromhidrosis under hematoxylin and eosin staining and ultraviolet fluorescence. To our best knowledge, this is the second case report in the literature of an adult male being affected by chromhidrosis, and the first of an adult male with black-colored malar cheek secretions in chromhidrosis.

Importance: Apart from the atypical mole phenotype, development of new melanocytic nevi in older individuals is uncommon and considered worrisome for melanoma. We performed a retrospective case series in a Veterans Affairs population from 1991 to 2013 to characterize blue nevi (BN) by patient age at biopsy, location, self-reported duration, and relation to prior or subsequent development of cutaneous melanoma., Observations: A total of 204 BN were identified in 194 predominantly male patients (90.7%) who had a mean (SD) age of 62.8 (14.4) years. Clinical duration of 10 years or less was reported by 90.3% of patients with available data (32.0%). Histopathologic examination classified 74.0% of BN as common, 1.5% as cellular, and 24.5% as combined type. No malignant BN were identified; however, 18 primary melanomas were diagnosed, most (72.2%) prior to blue nevus biopsy, including 38.9% in situ and 61.1% with mean (SD) Breslow thickness of 1.02 (0.99) mm., Conclusions and Relevance: The later patient-reported onset of BN suggests a potential alternative mechanism of nevogenesis compared with common acquired nevi and differs from prior reports of BN development in younger adults. The lack of association with melanoma in older individuals suggests that most benign-appearing BN may be safely observed, even in a cohort at higher risk for skin cancer.

Background: Reported recurrence rates for transected nonmelanoma skin cancer (NMSC) vary widely, and few studies have addressed recurrence of tumors followed clinically or treated with nonsurgical modalities., Methods: Retrospective review of dermatopathology records from January 1999 to January 2005 was conducted to identify biopsies or excision specimens with histologically transected basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) which were not subsequently excised. Patient and tumor characteristics associated with recurrence were analyzed in a subgroup of patients with predominantly 'low-risk' and/or minimally transected NMSCs. Prospective follow up was performed through March 31, 2008. Data was analyzed with Chi-square and Fishers exact tests and multivariate logistic regression., Results: Of 376 transected NMSCs, 27 (7.2%) recurred, including 20 (9%) of 223 BCCs and 7 (4.6%) SCCs in situ of 153 SCCs. The overall recurrence rate of the 124 minimally transected NMSCs was even lower (5.6%). Multivariate logistic regression identified three significant predictors of recurrence: tumor location on the head and neck (p = 0.041), tumor size (p = 0.00741) and superficial subtype of BCC (p = .035)., Conclusions: Although surgical excision of NMSC remains the standard of care, observation or nonsurgical treatment may be acceptable in many cases of incompletely excised low-risk or minimally transected NMSCs., (Copyright © 2009 John Wiley & Sons A/S.)

Background: Liposuction is one of the most frequently performed cosmetic procedures in the United States, but its cost and downtime has led to the development of noninvasive approaches for adipose tissue reduction., Objective: To determine whether noninvasive controlled and selective destruction of fat cells (Cryolipolysis) can selectively damage subcutaneous fat without causing damage to the overlying skin or rise in lipid levels., Methods: Three Yucatan pigs underwent Cryolipolysis at 22 sites: 20 at cooling intensity factor (CIF) index 24.5 (-43.8 mW/cm(2)), one at CIF 24.9 (-44.7 mW/cm(2)), and one at CIF 25.4 (-45.6 mW/cm(2)). Treated areas were evaluated using photography, ultrasound, and gross and microscopic pathology. Lipids were at various times points. One additional pig underwent Cryolipolysis at various days before euthanasia., Results: The treatments resulted in a significant reduction in the superficial fat layer without damage to the overlying skin. An inflammatory response triggered by cold-induced apoptosis of adipocytes preceded the reduction in the fat layer. Evaluation of lipids over a 3-month period following treatment demonstrated that cholesterol and triglyceride values remained normal., Conclusions: Cryolipolysis is worthy of further study because it has been shown to significantly decrease subcutaneous fat and change body contour without causing damage to the overlying skin and surrounding structures or deleterious changes in blood lipids.

Background: Cryolipolysis provides a method for noninvasive fat reduction that significantly reduces subcutaneous fat in a pig model without apparent damage to skin and surrounding structures. This study aimed to determine whether fat reduction in humans caused by cold exposure is associated with alteration in local sensory function or nerve fibers., Methods: In this study, 10 subjects were treated with a prototype cooling device. Fat reduction was assessed in 9 of the 10 subjects via ultrasound before treatment and at the follow-up visit. Sensory function was assessed by neurologic evaluation (n = 9), and biopsies (n = 1) were collected for nerve staining., Results: Treatment resulted in a normalized fat layer reduction of 20.4% at 2 months and 25.5% at 6 months after treatment. Transient reduction in sensation occurred in six of nine subjects assessed by neurologic evaluation. However, all sensation returned by a mean of 3.6 weeks after treatment. Biopsies showed no long-term change in nerve fiber structure. There were no lasting sensory alterations or observations of skin damage in any of the subjects evaluated., Conclusion: Noninvasive cryolipolysis results in substantial fat reduction within 2 months of treatment without damage to skin. The procedure is associated with modest reversible short-term changes in the function of peripheral sensory nerves.

Moisturizers are commonly used for routine skin care. This study assessed the effects of a moisturizer on barrier function, epidermal architecture, keratinocyte proliferation, and physiological regulation of the epidermis in photoaged but otherwise normal skin. Fifteen women with moderately photoaged forearms were treated twice a day for 4 weeks with a moisturizer containing dimethicone and glycerine. Baseline and post-treatment transepidermal water loss (TEWL) and ipsilateral forearm biopsies were obtained. Epidermal thickness, melanin levels, keratinocyte proliferation, and expression of keratins were evaluated. Induction of keratins 6 and 16, commonly associated with keratinocyte proliferation and wound healing, was observed. Epidermal thickness increased by 0.019 mm (P = 0.005), barrier function improved (TEWL decreased by 13%) and melanin intensity decreased (P = 0.004). Even nonxerotic, photoaged skin may appear younger, benefiting structurally and functionally from routine use of moisturizers containing dimethicone and glycerine.

Background and Objectives: Monopolar radiofrequency (RF) treatment is used by physicians to tighten and contour the skin of their patients. In many cases, patients have received prior treatment with other aesthetic modalities such as soft-tissue augmentation or they may wish to receive these treatment modalities simultaneously. Together, soft-tissue augmentation and monopolar RF treatment have the potential to restore tissue volume and improve facial laxity. To date, no published studies have documented the effects of RF treatment directly over soft-tissue fillers., Study Design/materials and Methods: We examined the tissue interactions of monopolar RF heating with five commonly injected fillers in a juvenile pig model. This is the first part of a two-part study. In this study, the interaction of monopolar RF and filler substances was examined over a period of 4 months. The five soft-tissue fillers examined were cross-linked human collagen (Cosmoplast), hyaluronic acid (Restylane), calcium hydroxylapatite (Radiesse), polylactic acid (Sculptra), and liquid injectable silicone (Silikon 1000)., Results: There was no apparent increase in the risk of local burns and no observable effect of RF treatment on filler persistence in the tissue. With monopolar RF treatment, an increase in fibroplasia and collagen deposition surrounding Restylane, Radiesse, and Sculptra was observed. When scored in a blinded fashion, the increase in collagen deposition was statistically significant for Radiesse., Conclusions: In this animal study, RF treatment had no observed adverse effect on filler collagen responses or persistence. Filler presence did not increase the risk of undesirable thermal effects with monopolar RF treatment. Further clinical studies are required to evaluate the effect of monopolar RF treatment over dermal fillers with respect to aesthetic outcome., ((c) 2005 Wiley-Liss, Inc.)

Worldwide, lentigo maligna melanoma (LMM) comprises 4%-15% of cutaneous melanoma and occurs less commonly than superficial spreading or nodular subtypes. We assessed the incidence of melanoma subtypes in regional and national Surveillance, Epidemiology, and End Results (SEER) cancer registry data from 1990 to 2000. Because 30%-50% of SEER data were not classified by histogenetic type, we compared the observed SEER trends with an age-matched population of 1024 cases from Stanford University Medical Center (SUMC) (1995-2000). SEER data revealed lentigo maligna (LM) as the most prevalent in situ subtype (79%-83%), and that LMM has been increasing at a higher rate compared with other subtypes and to all invasive melanoma combined for patients aged 45-64 and > or =65 y. The SUMC data demonstrated LM and LMM as the only subtypes increasing in incidence over the study period. In both groups, LM comprised > or =75% of in situ melanoma and LMM > or =27% of invasive melanoma in men 65 y and older. Regional and national SEER data suggest an increasing incidence of LM and LMM, particularly in men > or =age 65. An increased incidence of LM subtypes should direct melanoma screening to heavily sun-exposed sites, where these subtypes predominate.

Background: Lentigo maligna (LM) can histologically simulate dysplastic nevus (DN). Partial biopsy of LM may lead to misdiagnosis., Methods: One hundred and fourteen cases of LM and LM melanoma (LMM) were diagnosed at the Veterans Affairs Palo Alto Health Care System (1993-2002). Biopsy and excision specimens for 68 in situ and 28 invasive melanomas were classified as having predominant classical LM features, predominant DN-like morphology, or a mixed pattern., Results: Biopsy specimens demonstrated a predominant classical pattern in 38% (25/65) LM and 36% (10/28) LMM, predominant DN-like features in 43% (28/65) LM and 25% (7/28) LMM, and mixed pattern in 15% (10/65) LM and 29% (8/28) LMM. Most LM and LMM biopsies were partial. Significant DN-like features were present in 51% LM and 57% LMM excision specimens. Median age was 72 years for LM and 73 years for LMM, mean lesion diameters were 1.3 and 1.7 cm for LM and LMM, respectively, and 85% of LM and 75% of LMM cases were located on heavily sun-exposed sites., Conclusions: Misdiagnosis of LM or LMM as DN could have devastating results. Large pigmented lesions on sun-damaged skin in elderly individuals should warrant consideration of LM/LMM diagnosis, even in the setting of DN-like features histologically. Excisional biopsy may help to avoid misdiagnosis.

Background: Sebaceous carcinoma is a rare, aggressive neoplasm that arises from the adnexal epithelium of sebaceous glands and is commonly associated with Muir-Torre syndrome., Objective: The metastatic potential of extraocular sebaceous carcinoma warrants a thorough evaluation to establish the extent of disease., Methods: We describe a 55-year-old man who presented with an asymptomatic abdominal wall mass 3 years after definitive diagnosis of Muir-Torre syndrome., Results: A biopsy of the surgical specimen revealed sebaceous carcinoma., Conclusion: Dermatologists are crucial to the early recognition and diagnosis of extraocular sebaceous carcinoma. In our patient with documented Muir-Torre syndrome, continued surveillance allowed for prompt recognition and treatment of this associated cutaneous malignancy.

Injectable bovine collagen has proven to be safe and effective for the treatment of contour defects for more than 20 years. After intradermal exposure to bovine collagen, the most commonly reported side effect is hypersensitivity (incidence of approximately 3 percent to test and approximately 1 to 2 percent to subsequent treatment). The main purpose of this study was to evaluate tissue response and antibody production in bovine collagen-sensitive patients who were treated with human collagen (predominantly type I) implant. Twenty-seven patients with confirmed hypersensitivity to bovine collagen received a depot of human collagen implant and then were treated for facial contour defects on two to five separate occasions over a 9- to 12-month period and followed through 36 months. Measurement of antibody titers indicated that none of the subjects receiving human collagen implant developed antibodies against human collagen, even in the presence of positive antibody titers against bovine collagen. Histologic examination of the depot sites in these patients showed only mild inflammation. These findings indicate that treatment with human collagen did not elicit an allergic response in these subjects who had confirmed hypersensitivity to bovine collagen.

Background: Wound healing following a partial biopsy of basal cell (BCC) and squamous cell carcinomas (SCC) may induce tumor regression., Methods: Nonmelanoma skin cancer (NMSC) biopsy and re-excision specimens from 1994 to 2001 were reviewed for histologic evidence of scar vs. presence of residual tumor in excision specimens. Regressed and non-regressed tumors were analyzed to assess the influence of anatomic location, biopsy technique (punch vs. shave), histologic subtype of BCC or SCC, time interval between biopsy and excision, and patient age., Results: Nine hundred and ten excisions were performed for transected BCC or SCC, 217 (24%) of which showed scar with no residual tumor. Logistic regression analysis revealed significant differences in the regressed vs. non-regressed subsets. SCCs were more likely to regress than BCCs (40% vs. 20%, respectively, p < 0.00001). Independent of the NMSC type, tumors regressed more often following shave rather than punch biopsy (34% vs. 15%, respectively, p < 0.00001), as did tumors on the trunk and extremities compared with head and neck cases (31% vs. 21%, respectively, p < 0.01)., Conclusions: In our series, 24% of NMSCs transected on the initial biopsy showed no residual tumor in the excision specimens, implying that some event in the interval between biopsy and excision may lead to the eradication of residual tumor. The exact mechanism is unclear, but wound healing likely plays an important role.

Extracellular matrix hyaluronan is prominent during wound healing, appearing at elevated levels early in the repair process. It is prevalent throughout the course of fetal wound healing, which is scar-free, but decreases late in adult wound repair, that is often marked by scarring. To determine whether aberrant hyaluronan metabolism is associated with the excessive scarring that characterizes keloids, cultured fibroblasts derived from keloids and from the dermis of normal human skin and scar were compared. Levels of hyaluronan in 48 h conditioned media of keloid-derived cultures were significantly lower than in cultures of normal skin and scar fibroblasts. Profiles of hyaluronan polymer size were comparable in these two cell types, suggesting that excessive hyaluronan degradation was not involved. Hydrocortisone decreased hyaluronan levels approximately 70% in the conditioned media of both keloid and normal fibroblasts. Diminished hyaluronan accumulation in keloid-derived cells compared with normal fibroblasts was also observed in an in vitro wound healing model. Histolocalization of hyaluronan in keloids, normal skin, and scar samples confirmed the biochemical observations that the dermis of keloids, which comprises most of the scar tissue, contained markedly diminished levels of hyaluronan. Alterations in hyaluronan in the epidermis overlying keloids, however, were also observed. A modest increase in hyaluronan staining intensity was observed in the epidermis of keloids, as well as changes in the patterns of distribution within the epidermis, compared with that in normal skin and scar. Increased hyaluronan was present in the granular and spinous layers of the keloid epidermis Abnormalities are present apparently in both the overlying epidermis as well as in the dermis of keloids. Aberrations in signaling between keloid stroma and keloid epidermis may underlie abnormalities that contribute to the excessive fibrosis characteristic of these lesions.

Background and Objective: To compare the in vivo histologic effects of the pulsed carbon dioxide (CO(2)) and erbium:ytrium aluminum garnet (Er:YAG) lasers and to assess the effects of combining CO(2) and Er:YAG laser modalities during a single treatment session. We previously reported 10 patients treated with four laser regimens: CO(2) alone, CO(2)/Er:YAG, Er:YAG alone, Er:YAG/CO(2) with time points at 1 hour and 7 days between laser treatment and histologic analysis. This study found that the optimal treatment consisted of limited CO(2) laser passes followed by Er:YAG. This treatment produced less collagen injury, less thermal necrosis, and more robust epithelial and dermal fibrous tissue regeneration in the acute phase of healing. The present study examines the histologic changes resulting from the host healing response to laser treatment on long-term follow-up of 4-6 months., Study Design/materials and Methods: The Stanford University Committee on Human Subjects in Medical Research approved this study. Nine patients with actinic damage and indications for rhytidectomy volunteered for this interventional study in which each patient served as both experimental and control. The right preauricular area was treated at five sites with the following: (1) CO(2), (2) CO(2) followed by Er:YAG, (3) Er:YAG, (4) blended CO(2)/Er:YAG (Derma-Ktrade mark), (5) phenol. Each was subjected to full-face or sub-unit treatment. Each patient was followed up initially daily then weekly for healing of the full-face laser and for differences in healing of the five treatment areas. Five patients were selected for histologic evaluation. At 4-6 months, these patients underwent rhytidectomy with immediate removal of laser-treated skin, which was evaluated histologically by the study dermatopathologist, who was blinded to the treatment at each site., Results: CO(2) laser treatment produced the greatest thickness of neocollagen (0.27 mm; P < 0.05), the highest neocollagen density (P < 0.05), the greatest decrease in elastosis (27%), but took the longest time for healing and resolution of erythema and inflammation (up to 6 months). Er:YAG used alone produced the least collagen density, with the thinnest band of neocollagen (0.08 mm), but the most rapid resolution of erythema and inflammation (within 10 days). Combined CO(2)/Er:YAG treatments, including Derma-Ktrade mark and CO(2) followed by Er:YAG produced histologic changes that were intermediate, as well as recovery that was intermediate (resolution of erythema within 1 month); the development of neocollagen was greater in CO(2)-containing modalities than Er:YAG used alone by a statistically significant margin (P = 0.001). These histologic findings were corroborated by clinical correlation by examination of the five treatment spots in nine patients and in full-face treatments in 100 patients., Conclusion: Collagenesis is greatest with CO(2) and least with Er:YAG. Elastosis decreased to the greatest degree with CO(2), least with erbium, and to an intermediate extent with blended CO(2)/Er:YAG regimens (sequential and Derma-K). These changes from control are statistically significant with all regimens (P < 0.05). Blended CO(2)/Er:YAG treatments provide an optimal combination of the benefits of CO(2) but with lesser erythema and healing delay. Clinical and histologic findings change over time for different treatments. Thus, long-term histology is critical for predicting results of treatment.

A case of basal cell carcinoma with giant cells of the central epithelial and surrounding stromal components is presented. The lesion was an 8-mm dome-shaped papule on the ear of a 66-year-old man. The giant cells of the epithelial component shared the immunophenotype of the more typical cells of the basal cell carcinoma (keratin, smooth muscle actin, and bcl-2 positive), whereas the stromal giant cells were positive only for bcl-2. This case represents a peculiar variant of pleomorphic basal cell carcinoma, the significance of which is unknown.

Background: Laser treatment of skin following removal from human subjects has been the staple of laser research. However, no study has been done to assess the efficacy of ex vivo skin for predicting the behavior of laser treatments in living human tissue., Objective: To assess the validity of the ex vivo model by comparing histological characteristics of skin treated with laser prior to and following its removal in rhytidectomy., Study Design: Nonrandomized controlled intervention study in which each patient served as both experimental subject and control for different skin sites., Patients: Ten patients with actinic skin changes., Interventions: Patients underwent laser treatment to 4 left preauricular sites 1 hour prior to rhytidectomy as follows: carbon dioxide laser treatment alone, carbon dioxide laser treatment followed by erbium:YAG laser treatment, erbium:YAG laser treatment alone, and erbium:YAG laser treatment followed by carbon dioxide laser treatment. The skin was examined by a dermatopathologist blinded to the identity of each specimen. Untreated skin was also removed and immediately subjected to laser treatment identical to that employed in the in vivo skin. This skin was examined histologically., Main Outcome Measures: Regularity of ablation, depth of the necrotic zone, amount of skin removed, degree of collagen injury, and degree of inflammation., Results: There were significant differences between the ex vivo and in vivo groups. The ex vivo specimens demonstrated more than 10 times the irregularity of ablation of the in vivo specimens (irregularity index of 3.0 for the ex vivo group vs 0.25 for the in vivo specimens; P < .05). The incidence of collagen injury was slightly lower for the ex vivo group (1.0 vs 1.3), as was the degree of inflammation (1.4 vs 1.5). The greatest differences were the significantly smaller necrotic zone in the ex vivo specimens (51 vs 71 microns) and the smaller amount of skin removed (118 vs 234 microns). These findings were consistent for all 4 laser treatment regimens studied., Conclusions: Significant differences were found between the in vivo and ex vivo models. Irregularity of ablation in the ex vivo specimens was 10 times that in the living specimens, limiting histological accuracy in the ex vivo model. The ex vivo skin model underestimated the amount of tissue ablation. This suggests that an in vivo model should be adopted as the standard for laser research.

Background and Objective: To compare the in vivo histologic effects of the carbon dioxide (CO2) and erbium:yttrium aluminum garnet (Er:YAG) lasers. To ascertain the effects of combining CO2 and Er:YAG laser modalities during a single treatment session., Study Design/materials and Methods: Ten patients underwent laser treatment to four left preauricular sites 7 days prior to rhytidectomy as follows: CO2 alone, CO2/Er:YAG, Er:YAG alone, and Er:YAG/CO2. The right preauricular area was identically treated 1 hour prior to rhytidectomy. Laser treated skin was excised during rhytidectomy and was evaluated histopathologically in a blinded manner., Results: After 7 days, all groups were reepithelialized and showed equal neo-collagen formation. After 7 days, CO2/Er:YAG and Er:YAG alone had the least collagen injury and thickest epidermis and papillary dermis of all groups. Specimens lased 1 hour prior to excision showed the least collagen injury and thermal necrosis when treated with CO2/Er:YAG and Er:YAG alone. Four passes with CO2 removed 250 microm of tissue, while eight passes with the Er:YAG removed 160 microm of tissue., Conclusions: Limiting CO2 laser passes and ending with Er:YAG produces less collagen injury, less thermal necrosis, and more robust epithelial and dermal fibrous tissue regeneration. CO2 followed by Er:YAG has similar thermal necrosis and collagen injury as Er:YAG alone, presumably due to Er:YAG removal of CO2 induced thermal injury.

Over 200 basal cell carcinomas (BCCs) are biopsied and subsequently excised each year at the Veterans Affairs Palo Alto Health Care System (VAPAHCS). A focal infiltrative pattern developed in the region of the biopsy scar in the re-excision specimens of 20 cases out of approximately 400 BCCs (< 5%) examined histopathologically over a 2-year period. The patient population included predominantly male, elderly Caucasians (mean age 71), and all tumors fulfilled clinical and histologic criteria for nodular BCC at the time of initial punch or shave biopsy. No patient showed recurrence of tumor following simple re-excision with 2-3 mm surgical margins, with a mean follow up of 25.4 months after excisional surgery. These neoplasms had a more benign clinical course, possibly related to scar formation in healing sites of previously biopsied nodular BCC, rather than true aggressive-growth BCC. The authors conclude that a focal infiltrative pattern in a re-excision specimen may occur histologically as a scar-induced pattern which mimics an aggressive-growth BCC, but does not appear to have the same prognosis. We believe this is an important histologic observation, as recognition of biopsy scar changes in an excisional specimen of BCC may help to distinguish it from true aggressive-growth BCC.

Background: We have noted a high frequency of aggressive-growth basal cell carcinomas (BCCS) in our patient population. Subtypes observed with increased frequency include morpheaform, infiltrative, and micronodular., Objective: Our purpose was to examine the frequency of histologic subtypes of all BCCs seen in the dermatology clinics in the Veterans Affairs Palo Alto Health Care System in an 18-month period., Methods: We reviewed 432 consecutive primary BCC biopsy specimens taken from 252 patients., Results: Aggressive-growth BCC was observed in 20.7% of biopsy specimens, including 13.4% morpheaform, 5.7% infiltrative, and 1.6% micronodular subtypes. The mean age of the patient population was 70 years, with a standard deviation of 9.1 years., Conclusion: Our observed percentage of aggressive-growth BCC is substantially higher than in most other large studies. A high frequency of aggressive-growth BCC coupled with the increasing incidence of nonmelanoma skin cancer may have significant implications for future health care resource allocation.

The clinical, histologic, and immunohistologic features of 22 desmoplastic melanomas (DMM), 10 mixed desmoplastic and spindle-cell melanomas (DMM/SMM), and two cellular spindle-cell melanomas (SMM) were studied. Patients ranged in age from 35 to 91 years (mean, 67) and included 23 men and 11 women. Seventeen cases occurred in sun-damaged skin of the head and neck. 11 were on the extremities, and six on the trunk. Except for two cases, all were Clark's level IV or V. Twenty-two (65%) cases were associated with a recognizable overlying pigmented lesion. Thirty of 32 (94%) DMM and DMM/SMM were clearly positive for S100. S100 staining was limited to < 5% of the spindle cells in two DMM/SMM. All DMM were negative when stained with HMB45. Three DMM/ SMM were immunoreactive with HMB45, as were both SMM. CD68 staining was limited to < 5% of the spindle cells in two of 32 DMM and DMM/SMM and 20% of the cells in one of two SMM. Nine (32%) DMM and DMM/SMM contained significant numbers of spindle cells immunoreactive for SMA but not desmin. In five cases, the number of actin-positive spindle cells. Two color stains for SMA and S100 demonstrated that these smooth-muscle actin positive cells constituted a separate spindle-cell population, consistent with reactive myofibroblasts. This study indicates that the immunohistologic features of desmoplastic melanoma differ from those of conventional melanoma. If a problematic spindle-cell skin lesion is a suspected melanocytic process, HMB45 is unlikely to provide confirmatory (or exclusionary) evidence for the diagnosis of DMM. Similarly, because of the variability in S100 expression in this neoplasm, the absence of S100 staining should not be relied on too heavily to exclude DMM if the clinical and histologic features favor that diagnosis. Caution should be exercised in the interpretation of numerous actin-positive spindle cells in isolation of additional confirmatory or exclusionary data as desmoplastic melanomas may contain significant numbers of these cells.

We describe a 40-year-old white man with a red-brown, indurated plaque on the proximal aspect of his right thigh. The lesion had been present since birth, and the patient had a 20-year clinical history of recurrent cellulitis in the same area. The histopathologic features of the lesion included permeation of the dermis by flattened, endothelium-lined channels without cellular atypia, hemorrhage, or inflammation. The endothelial cells were stained intensely with monoclonal antibody anti-CD34 (clone MY10). In addition, antibodies to factor VIII antigen, HLA-DR, smooth muscle actin, ICAM-1, and the lectin Ulex europaeus labeled the luminal cells. The basement membrane of the channels stained with anti-type IV collagen and laminin. Desmin-positive cells were abundant adjacent to the channels. Factor XIIIa stained both mononuclear cells and occasional dendritic cells in the perivascular area. Ki-67 immunolabeling could not be demonstrated on fresh or frozen tissue. Electron microscopy revealed the presence of both tight junctions and a well-formed, continuous basement membrane but the absence of Weibel-Palade bodies.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with a high incidence of colon cancer. Dysplasia is a precursor to carcinoma and a predictor of malignant potential; epithelia containing high-grade or severe dysplasia is most likely to develop cancer. The cellular oncogene c-src and its viral homologue v-src (the transforming gene of Rous sarcoma virus) encode 60-kD cytoplasmic, membrane-associated protein tyrosine kinases. For the viral protein or transforming mutants of the cellular protein (Src), a close correlation exists between elevated tyrosine kinase activity and malignant transformation of cells. Previously, we and others observed elevated Src activity in sporadic colon carcinomas and benign adenomas at greatest risk for developing cancer (those with large size, villous architecture, and/or severe dysplasia). Here we report that Src activity and protein abundance are also elevated in neoplastic UC epithelia. Activity is highest in malignant and severely dysplastic epithelia, and 6-10-fold higher in mildly dysplastic than in nondysplastic epithelia. Thus, Src activity is elevated in premalignant UC epithelia, which is at greatest risk for developing cancer. The data suggest that activation of the src proto-oncogene is an early event in the genesis of UC colon cancer.

Desmoplastic neurotropic malignant melanoma is a rare spindle cell variant of malignant melanoma. This chapter reviews its clinical presentation; histologic, immunohistochemical, and ultrastructural features; differential diagnosis; and critical therapeutic issues.

In a previous study, we reported on the observation of a relatively specific, linear body in the roofs of bullae from cases of porphyria cutanea tarda. In the present study, we expand on these observations to show the presence of these bodies in lesions of pseudoporphyria cutanea tarda and erythropoietic protoporphyria. Furthermore, we have applied immunoperoxidase techniques using antibodies to type IV collagen and laminin to show that they are composed of basement membrane material. Because the segmented, elongated shapes of these bodies reminded us of the larvae of butterflies, we coined the term "caterpillar bodies" to describe them. These bodies are similar in their composition to the Kamino bodies of Spitz's nevi, cylindrical bodies in adenoid cystic carcinoma, Civatte bodies of lichen planus, and the collagenous spherules seen in a number of conditions, and may provide a unique clue to the diagnosis of the porphyric bullous eruptions.

Background: Poor interobserver reproducibility in diagnosing and grading dysplastic melanocytic nevi is often cited as evidence against the ability of pathologists to recognize such an entity., Objective: We attempted to examine the diagnostic profiles of melanocytic lesions of two dermatopathologists in a stable population base., Methods: All 2600 melanocytic neoplasms were diagnosed at Stanford University Medical Center during the past 4 years by one dermatopathologist from 1987 to 1989 and a different dermatopathologist in 1990 and 1991. The two independently evaluated these lesions unaware of the other's criteria., Results: The diagnostic profile of the two pathologists shows a striking degree of similarity: 76.7% versus 75.3% of all nevi were diagnosed as acquired melanocytic nevi, 8.8% versus 12.0% were diagnosed as mildly dysplastic, 7.0% versus 6.8% as moderately dysplastic, and 2.7% versus 1.6% as severely dysplastic., Conclusion: Our findings suggest that the two pathologists are using reproducible criteria for diagnosing and grading dysplastic nevi.

An association between erythema multiforme and herpes simplex virus infection has been supported by clinical studies and by the detection by immunofluorescence of herpes viral antigen in sera and skin biopsy specimens of patients with erythema multiforme. In rare cases, the virus has also been isolated in cultures of skin biopsy specimens of erythema multiforme. To investigate further the association between erythema multiforme and herpes simplex virus, we used the polymerase chain reaction for herpes simplex virus to examine skin lesions from patients with erythema multiforme. In this study herpes simplex virus DNA was detected in 11 of 31 biopsy specimens of erythema multiforme; six additional cases showed equivocal amplification results, which is suggestive of low amounts of viral DNA. Seven skin and mucosal biopsy specimens with the histologic changes of herpes virus infection served as positive controls: all were positive for herpes simplex virus DNA. Viral DNA was not detected in control biopsy specimens from skin excised for unrelated conditions. These studies support the association of herpes simplex virus in the pathogenesis of some cases of erythema multiforme. The polymerase chain reaction provides a quick and effective method of detecting herpes simplex virus in lesions of herpes-associated erythema multiforme. Furthermore, the polymerase chain reaction may delineate those cases of erythema multiforme that are etiologically related to herpes virus infection and therefore might be treated with acyclovir to prevent recurrence.

The two cases of the superior vena caval syndrome described illustrate the problem of making a diagnosis and of determining the etiology of this syndrome. The cutaneous manifestations were typical of the syndrome and included the sudden onset of facial and upper extremity edema, erythema, and telangiectasia. The causes of the syndrome cannot be recognized from the clinical presentation. In one of our cases, the cause was only determined at autopsy and proved to be an unusual benign cause, idiopathic thrombosis, masquerading as a malignant tumor; the other case was caused by an actual malignancy. The manifestations of the syndrome should alert the physician to determine its cause in order that appropriate therapy may be instituted as rapidly as possible.

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.

A patient had numerous cysts over almost all of his skin surface. The lesions were persistently infected, painful, and odorous, and were contributory to the patient's psychological problems. The cysts were histologically determined to be of the steatocystoma multiplex variety. Several therapeutic modalities were used but only surgical incision, drainage, and electrocautery were beneficial.

The first known case of Kartagener syndrome associated with glomerulonephritis is reported. Mesangiocapillary glomerulonephritis was diagnosed in this patient several months before her death. This report also includes a review of the recent literature dealing with Kartagener syndrome and mesangiocapillary glomerulonephritis and a consideration of the possible relationship of infection to the cause of mesangiocapillary glomerulonephritis.

Cutaneous vascular proliferations that clinically or pathologically resemble Kaposi's sarcoma, pyogenic granuloma, or histiocytoid (epithelioid) hemangioma may occur in patients with human immunodeficiency virus infection. These lesions, which respond well to antibiotic therapy, harbor bacilli similar to the agent of cat scratch disease. We evaluated 21 biopsy specimens from 13 patients with this condition, which we have called "bacillary angiomatosis." The architecture resembled that of lobular capillary hemangioma (pyogenic granuloma), but the endothelial cells were often larger, polygonal, and sometimes markedly atypical. The presence of neutrophils, leukocytoclastic debris, and granular material (bacteria), and the absence of either spindled cells, bizarrely shaped vascular channels, or hyaline globules help to distinguish bacillary angiomatosis from Kaposi's sarcoma. By electron microscopy, the protuberant endothelial cells were different from those of histiocytoid hemangiomas in that aggregates of intermediate filaments were absent, while numerous Weibel-Palade bodies were present. The immunophenotype of the endothelial cells was distinct from that of Kaposi's sarcoma; almost all cells showed both Factor VIII RAg and Ulex europaeus lectin positivity. Enzyme histochemistry also showed a pattern distinct from Kaposi's sarcoma. Bacillary angiomatosis presents a unique constellation of clinical and microscopic findings. It is important to be aware of these characteristics, because these lesions are easily treatable with antibiotic therapy.

Cutaneous lesions develop frequently in patients infected with human immunodeficiency virus (HIV). We describe the clinical features of four patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex who developed angiomatous nodules involving skin and bone, 2 of whom were scratched by a cat. Some of these lesions were clinically indistinguishable from Kaposi sarcoma. When examined with Warthin-Starry staining and electron microscopy, these nodules were noted to contain numerous clumps of a bacterium. Immunoperoxidase staining with an antiserum raised against the cat-scratch disease bacillus stained these organisms in all patients. Cat-scratch disease is usually a self-limited infection, but complicated or prolonged infections have been described in both normal and immunocompromised hosts. In our patients infected with HIV, manifestations of systemic cat-scratch disease included angiomatous nodules, severe systemic symptoms of fever, chills, night sweats and weight loss, elevated erythrocyte sedimentation rate, and decreased hematocrit. Cutaneous lesions involved the face, trunk, and extremities and numbered 2 to greater than 60; osseous lesions involved the fibula, radius, femur, and tibia, and were present in two of four patients. Treatment with x-ray therapy, intralesional vinblastine, penicillin, dicloxacillin, cephradine, and nafcillin had no effect on any lesions; however, treatment with erythromycin, doxycycline, or antimycobacterial antibiotics resulted in complete and rapid resolution of the cutaneous and osseous lesions, and the accompanying signs and symptoms of systemic infection. In patients with AIDS or AIDS-related complex, angiomatous nodules should be carefully evaluated for the presence of this organism, which can be treated and cured with antibiotic agents.

Recent reports indicate an increased incidence of Kaposi's sarcoma in young homosexual men. In contrast with the form of the disease seen in the elderly, in which skin involvement is usually confined to the lower extremities, lymph node involvement is rare, and disease progression is relatively slow, Kaposi's sarcoma in young homosexual men is characterized by diffuse skin and lymph node involvement and a fulminant disease course.

A 47-year-old black man had typical papulonodular lesions of lymphomatoid papulosis (LyP) with concurrent plaque-stage mycosis fungoides (MF). Both diagnoses were confirmed histologically. This supports the concept that LyP is part of the spectrum of cutaneous T-cell lymphoproliferative disorders. The patient also had a large nodule and a deeply infiltrated plaque, each of which exhibited a deep granulomatous reaction. These were interpreted as representing granulomatous MF. Clinically, there was an evolution from a predominance of LyP lesions to a predominance of MF plaques. Topical carmustine therapy resulted in a substantial decrease in the number and size of both LyP and MF lesions. Both lesion types involuted with hypopigmentation.

Two new cases of primary extraosseous Ewing's sarcoma of the spinal epidural space, and their histogenesis and differential diagnosis are described. The diagnosis of Ewing's sarcoma, which is essentially an undifferentiated tumour, depends largely on the exclusion of several other neoplasms with morphological similarities. With these two cases, 43 extraosseous Ewing's sarcomas have been reported to date, seven of which were epidural in location.

Papular and nodular skin lesions that clinically resembled Kaposi sarcoma, but histologically showed a distinct epithelioid haemangioma-like appearance, were noted in seven patients with the acquired immunodeficiency syndrome. Clusters of bacteria that had the structure of gram-negative rods were identified within each of the vascular proliferations by electron microscopy. The bacteria did not stain with the Brown-Brenn, acid-fast, or other histochemical stains for infectious organisms, but did stain with Warthin-Starry--ie, the staining profile was that described for the cat scratch disease (CSD) bacillus. Immunoperoxidase staining, using antisera raised in rabbits against cultured CSD bacillus, showed a positive reaction with the bacterium in all five cases tested. The two surviving patients have both given histories of having been scratched by a cat. In several patients, the vascular lesions regressed after therapy with antibiotics appropriate for CSD bacillus infection.

An optic nerve swelling that was thought clinically to represent a lymphomatous infiltrate of the nerve head developed in a 51-year-old man with histiocytic lymphoma. Histologic examination of the eyes showed the presence of cytomegalovirus (CMV) in the nerve head, but no lymphoma cells. Tru lymphomatous invasion of the nerve head in systemic lymphoma is probably very rare. This case points out an unusual manifestation of adult CMV infection, and a new concern in patients with compromised immune systems.