Entire Dermis Research Articles

The Evolution of Osseous Metaplasia in Localized Cutaneous Nephrogenic Systemic Fibrosis: A Case Report

Gadolinium (Gd) is associated with nephrogenic systemic fibrosis (NSF), a severe disorder mimicking scleroderma with involvement of the skin, lungs, heart, liver, and muscles. There is strong evidence that specific Gd-containing contrast agents (GCCAs) used in magnetic resonance imaging can cause NSF when administered to patients with chronic kidney disease. We present the 8-year history of cutaneous NSF with osseous metaplasia that occurred in a 56-year-old man with dialysis-dependent renal failure who was exposed to GCCA [gadopentate dimeglumine (Magnevist; Bayer Schering Pharma AG, Pittsburgh, PA)]. Three months after exposure to GCCA, he developed pruritic, pigmented patches that slowly coalesced and darkened over 8 years. Although not recognized at onset, skin biopsy showed typical histology of NSF affecting the entire dermis: CD34/procollagen I spindle cells associated with fibrosis. Biopsy performed 6 years later showed superficial scar-like fibrosis that was CD34/procollagen I and had numerous elastocollagenous balls (refractile elastic fibers surrounded by coarse collagen). Biopsy 7 years later showed the superimposition of osseous metaplasia on elastocollagenous balls. Both of these later biopsies had typical NSF histology affecting the deep dermis and subcutis. Over time, there was progressive diminishment of CD34 and procollagen I+ cells and an increase in FXIIIa+ and CD68 cells. Scanning electron microscopy and energy-dispersive x-ray spectroscopy showed Gd deposits in all areas of typical NSF histology but not in the regions of scar-like fibrosis, elastocollagenous balls, or osseous metaplasia. We suspect that the later changes may represent a late, involuting stage of NSF.

Morphology of skin incubation in Pipa carvalhoi (Anura: Pipidae)

South American Pipidae show a unique reproductive mode, in which the fertilized eggs develop in temporarily formed brood chambers of the dorsal skin after eggs have been deposited on the back of the female. We studied the skin incubation of Pipa carvalhoi using light microscopy and scanning electron microscopy. The skin consists of a stratified epithelium with a one-layered stratum corneum, and the dermis. The dermis of the dorsal skin of nonreproductive and reproductive females lacks a distinct stratum compactum, which is typical for most anuran skins. The entire dermis shows irregularly arranged collagen bundles like a stratum spongiosum. Before egg laying, the skin swells, primarily by thickening and further by loosening of the middle zone of the dermis. In the epidermis, large furrows develop that are the prospective sites of egg nidation. The epidermis, which forms a brood chamber around the developing egg becomes bi-layered and very thin and lacks a stratum corneum. Further, the dermis loosens and becomes heavily vascularized. Egg carrying females do not have mature oocytes in their ovaries indicating a slow down or interruption of egg maturation during this period. Similarities with the brood pouch of marsupial frogs are discussed.

Annular leucocytoclastic vasculitis

Leucocytoclastic vasculitis (LV) is characterized by necrotizing inflammation around small blood vessels, composed mainly of neutrophils and their debris. The skin lesions of LV are polymorphous, but an annular variant is rare. Four previous reports have named this variant 'annular LV' (ALV) and in this paper, we report two additional cases. Patient 1 was a 80-year-old man, who presented with pruritic, erythematous target lesions on his legs, soles, abdomen and axillae; histological examination showed typical LV throughout the entire dermis. Oral prednisolone 15 mg daily rapidly resolved the patient's symptoms. Patient 2 was a 64-year-old man, who was referred to our hospital because of multiple purpuric target lesions on the buttocks, right thigh, lower legs, upper arms and forearms. Histopathology revealed LV throughout the entire dermis. Oral prednisolone 20 mg daily rapidly resolved the lesions. We categorized these cases morphologically as ALV and clinically as small-vessel vasculitis. ALV is not a distinct condition, but includes a broad range of small-vessel vasculitides.

Foreign Body Granuloma Due to Matridex Injection for Cosmetic Purposes

A new resorbable filler, Matridex, became commercially available during the last years with scarce evidence regarding side effects. A 43-year-old woman complained of multiple, painful, reddish, nonulcerated, hard nodules on both cheeks and periocular regions. Four weeks before, she had been injected by a general practitioner with Matridex for aesthetic purposes to correct wrinkles in the same areas of the nodular eruption. Histopathology showed a diffuse suppurative granulomatous reaction with the presence of multinucleate giant cells and many neutrophils involving the entire dermis. No areas of caseation were observed. The inflammatory granulomatous reaction surrounded 2 different types of nonpolarizing, bluish, exogenous material: one arranged in filamentous structures and the second composed by large spherical particles. All nodules were incised and drained; the patient received systemic antibiotic treatment for 2 consecutive weeks. The nodules progressively regressed and almost complete resolution was seen after 6 months. Matridex is a new resorbable filler constituted by a mixture of nonanimal-stabilized hyaluronic acid (HA), cross-linked HA, and dextranomer microspheres. Foreign body reactions have been described in association with other HA fillers, but a granulomatous reaction after the injection of Matridex has not been reported yet. Interestingly, in our patient, we were able to identify both fragments of HA: the filamentous particles and the spherical particles of dextranomer microspheres within the infiltrate, these last giving a characteristic and recognizable appearance to the histopathological picture.

Dermal sheet preparations in the evaluation of dermal innervation in Parkinson’s disease and multiple system atrophy

Evaluation of dermal nerve fibers in conventional vertical sections is difficult because of the small number of fibers available for examination. In this study, we evaluated dermal sheet mounts for fibers in which the majority of fibers can be visualized. We compared the dermal small fiber density in six Parkinson's disease (PD) and six multiple system atrophy (MSA) patients using dermal sheet preparations (DSP). DSP are based on epidermal-dermal separations and immunostaining of the entire dermis by the nerve growth factor receptor p75 antibody that stains both autonomic and sensory fibers. The small fiber density was reduced in PD compared with MSA (p < 0.0001), suggesting the presence of small fiber neuropathy in PD. DSP offer a unique method of evaluation of dermal nerve fibers. This method can be used to evaluate small nerve fibers in many neurological disorders such as MSA and PD.

Pigmented trichoblastoma with sebaceous hyperplasia

Trichoblastoma is a rare benign trichogenic tumour with epithelial and mesenchymal components recapitulating the germinal hair bulb and associated mesenchyme. A 50- year- old male patient presented with slowly enlarging circumscribed solid nodule measuring 4x3x4.5 cm over the tip of the nose. Microscopy of tumour revealed nodular tumour spanning the entire dermis with collection of mesenchymal cells resembling follicular papilla. Areas of pigmentation and sebaceous hyperplasia were noted. There is a need for differentiation of this tumor which is benign, from other pigmented tumors having basaloid arrangement of cells such as basal cell carcinoma.

Primary cutaneous spindle cell B‐cell lymphoma with multiple figurate erythema‐like manifestation

We report a 68-year-old Korean man presenting with asymptomatic erythematous polycyclic annular firm plaques on his back that spread to the right shoulder. Histopathologic examination showed dense, diffuse infiltrates involving the entire dermis, consisting of atypical lymphocytes with many centrocytes and a few centroblasts. Spindle-shaped cells with elongated, twisted nuclei containing dispersed chromatin were also seen. Immunohistochemical analysis showed that all of the cells were strongly positive for CD20, CD21, CD79a and CD45, while they were negative for CD3, CD5, CD10, CD23, CD35, CD43, CD45RO and CD68. The spindle cells were also negative for smooth-muscle actin, desmin, S-100 and CD34. They consistently expressed nuclear bcl-6, but did not express bcl-2, multiple myeloma-1 and p16. We diagnosed him with primary cutaneous spindle cell B-cell lymphoma (PCSBCL) and treated him with six cycles of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab (R-CHOP) chemotherapy; his skin lesions disappeared completely. Immunohistochemical profiles suggest that PCSBCL is a variant of primary cutaneous follicle center lymphoma.

014 Epiboly in Bioengineered Skin as a Novel Method for Studying Epidermal Migration and Determining Construct Viability

There are only a few models for studying epidermal migration in vitro, and their interpretation is made difficult by reliance on cell monolayers and the choice of a specific substrate. In this study, the process of keratinocyte migration and epiboly were investigated by using a bilayered bioengineered skin construct, consisting of human neonatal foreskin keratinocytes and dermal fibroblasts (Apligraf, Organogenesis, Canton, MA). At baseline, 6-mm punch biopsies of the construct were placed in serum-free media (AIM-V) or DMEM with or without 10% FBS. At varying time points the bioengineered skin samples were processed and analyzed by histology and immunostaining. By 72 hours, in a time-dependent manner, the epidermis had migrated over and enveloped the entire dermis (full epiboly). Full epiboly was partially inhibited by serum and was maximal in serum-free medium. Epiboly was preserved 5 days after stated expiration date and was equivalent to that seen in unexpired construct when stored at room temperature. The process of epiboly was downregulated in a dose-dependent manner by neutralizing antibodies to EGF and TGF-beta 1. The migrating epithelium was characterized by decreased keratinocyte proliferation (as per Ki67 immunostaining) and increased expression of vitronectin (epibolin). Increasing concentrations of antibodies of vitronectin blocked the process of epiboly, as did antibodies to the alpha5-betaV integrin receptor, which mediates vitronectin-driven keratinocyte locomotion. Interesting, epiboly was also blocked by preseeding human dermal fibroblasts on the dermal side of the construct. We propose that the process of epiboly in this model can be used to better understand and assess the mechanisms involved in keratinocyte migration and may be used as an assay for establishing construct functional viability.

Desmoplastic Malignant Melanoma: A Clinicopathologic Analysis of 113 Cases

Desmoplastic melanoma (DM) is a rare variant of spindle cell melanoma, which usually develops in sun-damaged skin of elderly patients. Often the lesion is nonpigmented and frequently mistaken for a nonmelanocytic proliferation, which delays diagnosis and treatment and therefore worsens the prognosis. The spindle shape of neoplastic melanocytes, the prominent desmoplasia, and the frequent neurotropism of neoplastic melanocytes are its most characteristic histopathological features. We have studied the clinicopathologic features of 113 cases of DM. The mean age of the patients was 71.1 years; 48% of the patients were males and 52% were females. The neoplasm was located on the head in 72% of the cases. Malignant melanoma was the initial clinical diagnosis in only 27% of the cases. Histopathologically, all lesions appeared as poorly demarcated neoplasms that involved the entire dermis and often extended into the subcutaneous tissue. The neoplasms were composed of ill-defined fascicles of spindle cells. Desmoplasia was defined as the presence of spindle cells associated with a fibrotic stroma. Fifty-one cases (45%) were classified as "pure DM" when the lesion was entirely desmoplastic, and 62 cases (55%) were considered as "combined DM" when a recognizable desmoplastic component was seen in an otherwise conventional malignant melanoma. In 81% of the cases, an atypical intraepidermal melanocytic component (in situ malignant melanoma) was identified, whereas in the remaining 19% of the cases the intraepidermal component was lacking. Seventy-one percent of the cases were histologically amelanotic, 23% showed a small amount of pigment, and only 6% were heavily pigmented. Neural involvement was identified in 40/113 cases (35%), predominantly in the thickest tumors. Lymphoid nodules, found in 42/113 cases (37%), were significantly more frequent in pure DM than in combined DM (53% vs 24%). The null hypothesis of homogeneity of the "pure" and "combined" subgroups should be rejected (P < 0.002). Solar elastosis, with variable intensity, was seen in 82% of the cases. Mean Breslow thickness was 4.1 mm (4.6/3.7 mm, in the pure/combined subgroups, respectively), median was 4.0 mm (4.0/3.0 mm); Breslow thickness ranged from 0.3 to 11.0 mm, with half of the cases thicker than 4 mm. Only 4% of the cases showed Clark level below IV. The predominant neoplastic cells consisted of spindle-shaped melanocytes in 85% of the cases, whereas the remaining 15% of the cases demonstrated round neoplastic cells forming the main mass of the neoplasm. The mitotic rate of the neoplastic cells was low in 72% of the cases, 23% had an intermediate mitotic rate, and 5% showed a high mitotic rate. On follow-up, 55/113 patients (49%) (with an average of 55 months) demonstrated persistence of the disease. About 4% had local recurrences, 2% of lymph node invasion, 9% systemic metastases, and 12% died from the disease (2 cases of pure DM and 5 cases of combined DM). Although a better prognosis has been postulated for DM when compared with conventional cutaneous malignant melanomas of the same thickness, in most cases, a DM is diagnosed only in established long-standing and thick melanomas. Therefore, dermatologists and dermatopathologists should be more aware of this clinicopathologic variant of cutaneous malignant melanoma.

Large cell transformation mimicking regional lymphomatoid papulosis in a patient with mycosis fungoides

A 57-year-old Japanese man with tumor-stage mycosis fungoides suddenly presented multiple small papules on the right chest. Histopathology of a biopsy specimen from the papules revealed medium-to-large pleomorphic lymphoid cells throughout the entire dermis but not in the epidermis, and the large cells expressed CD30 antigen. These newly-developed papules underwent spontaneous remission in the following 3 months. We reviewed the reported cases of mycosis fungoides, which showed CD30-positive large cell transformation and those of CD30-positive lymphoproliferative disorders associated with mycosis fungoides.

Efficiency of controlled topical delivery of silver sulfadiazine in infected burn wounds

The present study is designed to assess the potential benefits of controlled delivery of silver sulfadiazine from collagen scaffold (SSDM-CS) in infected deep partial thickness burn wounds in which epidermis is lost completely and the entire papillary dermis and most of the recticular layer of the dermis is lost. Infection induced by inoculating 10(7) colony forming units (cfu) of Pseudomonas aeruginosa caused significant increase in wound size (20%) till day 15, which decreased significantly from day 9 by SSDM-CS treatment, showing complete healing by day 27 (control > or = 37 days). Early subsidence of infection (<10(2) cfu, day 9) by SSDM-CS resulted in faster epidermal resurfacing and fibroplasia, whereas heavy microbial load (>10(7) cfu, day 9) in controls caused severe inflammatory cellular infiltration. Persistent infection triggered early expression of proinflammatory cytokines intereukin-6, intereukin 1-beta, and tumor necrosis factor-alpha, lasting until day 9, whereas cytokine level decreased in SSDM-CS-treated group by day 6. Infection exacerbated expression of active matrix metalloproteinases (MMPs)-2 and -9 in controls (day 15), while SSDM-CS positively modulated MMP-2 and -9 with faster decline in their levels (day 12). Inherent nature of the dressing to maintain drug level at equilibrium therapeutic concentration (51.2 microg/mL) for prolonged time (72 h), below systemic toxic limits (20 microg/dL, serum level), accelerated the magnitude and sequence of reparative events.

Necrobiotic xanthogranuloma with paraproteinemia; an atypical case

Necrobiotic xanthogranuloma (NXG) is a rare marker for paraproteinemia. An 86-year-old woman had a one year history of large red-yellow to brown annular plaques involving all limbs. Biopsies showed a non-palisading granuloma with numerous multinucleated giant cells showing prominent elastophagocytosis and extensive areas of necrobiosis throughout the entire dermis. Complete loss of elastic fibers was observed in the central atrophic area of an annular plaque. Small vascular thromboses were also present. Laboratory findings revealed paraproteinemia of IgG-lambda type. Immunohistochemical staining detected the presence of roughly equal numbers of IgG-lambda-and IgG-kappa-staining plasma cells in the dermis. We diagnosed NXG with paraproteinemia with monoclonal gammopathy (IgG-lambda type) of unknown significance.

Surveillance, Epidemiology, and End Results (SEER) Database Analysis of Microcystic Adnexal Carcinoma (Sclerosing Sweat Duct Carcinoma) of the Skin

Microcystic Adnexal Carcinoma (MAC), also known as sclerosing sweat duct carcinoma, malignant syringoma, syringoid carcinoma, and trichofolliculoma with perineural invasion, is a very rare cancer of the skin. It has been described previously in small case reports and retrospective series, and is thought to be a slow growing, locally aggressive and recurrent cancer. Prior reports have also noted a predilection for the head and neck. In addition, prior radiotherapy is thought to be a risk factor for MAC. This is the largest report of MAC in the literature. The National Cancer Institute (NCI) SEER 1973-2003 database was investigated, and patients with sclerosing sweat duct carcinoma of the skin were detected. A descriptive analysis was performed, investigating age, gender, site of disease, use of radiation, extent of surgery, and reason for death. Overall survival was calculated by using the Kaplan-Meier method. Relative survival was calculated in SEER∗Stat 5, using age-, race-, gender- and year of diagnosis-matched U.S. mortality data. MAC of the skin was recorded in 164 patients. Ten patients received radiation. Ninety-two percent of patients received surgery. Sixty percent of subjects were female. Median age at diagnosis was 67.5 years old. The median recorded tumor size was 15 mm (range 1 mm–150 mm), though tumor size was not recorded for 102 patients. Race distribution was 91% white, 4% black or asian/pacific islander, and 5% unknown/other. As expected, the site of disease predominated in the head and neck (74%). The remaining reported sites included trunk 10%, upper limb/shoulder 9%, and lower limb/shoulder 6%. Seventy-six percent of disease was confined to the dermis or localized but not otherwise specified. Seven percent had invaded through the entire dermis, and 7% had invaded locally to underlying soft tissue and bone. Disease invasion was unknown in 9%. There was no recorded metastatic disease though these were possibly coded as non-skin sites and not captured in our analysis. Lymph nodes were removed in only 6 cases. The 5-year overall survival was 90% ([95% CI: 80%–95%]). The 5 and 10-year relative survival 99.6% (SE: 3.1% and 3.9%, respectively). All 8 deaths occurred before 3 years (Fig.). This SEER database analysis confirms previously published characteristics. MAC tends to occur in the skin of the head and neck (74%), in whites (91%), and in females (60%). It is locally invasive and rarely metastasizes to lymph nodes. Overall and relative survival is excellent. Radiation is rarely used for treatment.

Heat shock proteins 47 and 70 expression in rodent skin model as a function of contact cooling temperature: Are we overcooling our target?

The degree of protective cooling required during laser therapy to achieve an optimal result is unknown. The expression of heat shock proteins, Hsp47 and Hsp70, were examined in the epidermis and dermis as biomarkers to quantify the degree and depth of tissue affected by non-ablative laser treatment using variable protective cooling parameters. Twenty-one male Sprague-Dawley rats were treated with a 1,319 nm Nd:YAG laser using a sapphire cooling plate attached to the hand piece. A 4 cmx4 cm area on each side of the rat was treated with the same energy and pulse settings, with variable contact cooling. Protective cooling parameters, for each degree increment, ranging from 0 to 25 degrees C were studied. Immunohistochemistry (IHC), Western blot and PCR were performed to evaluate the effects of superficial cooling on Hsp47, and Hsp70 expressions. Our data showed the extent of topical cooling needed to produce a thermal effect at different depths in the dermis, quantified by the expression of Hsp47 and Hsp70. Significant Hsp expression was observed with cooling of 13 degrees C and warmer; no identifiable cellular reaction was observed when cooling below 5 degrees C. There was no evidence of epidermal injury when treating the skin with any protective cooling ranging from 0 to 25 degrees C. Our data would suggest contact cooling temperatures 5 degrees C and below completely protects through the entire dermis. There was no evidence of epidermal injury with protective cooling at any temperature between 0 and 25 degrees C. Warmer temperatures are safe and adequately protect the epidermis in this model.

Primary localized cutaneous amyloidosis with unusual clinical features in a patient with Sjögren's syndrome

A 69-year-old woman presented with a 2-year history of an eczematous lesion covering the genital area. Histopathological examination showed deposits of amorphous, eosinophilic material and an infiltrate of plasma cells through the entire dermis into the subcutaneous fatty tissue. Congo red-stained deposits showed apple-green birefringence with polarizing microscopy. On immunohistochemistry, the deposited material was positively stained with anti-lambda light chain antibodies but not with anti-lambda light chain. A diagnosis of primary localized cutaneous amyloidosis (PLCA) was made, and the patient was also diagnosed as having Sjögren's syndrome (SjS) based on clinical and laboratory findings. The lesion of PLCA has spontaneously regressed over a period of 18 months. We report a unique case of PLCA and SjS that clinically demonstrated genital eczematous features and spontaneous involution, and we also describe a possible association between PLCA and SjS.

Infiltrated plaques on the face and back

A 31 year-old woman, previously healthy, presented a four-month history of enlarging plaques on the face and back without any constitutional complaints. She referred to one unprotected heterosexual contact but denied any past history of sexually transmitted infections. Physical examination revealed multiple, tumid, nontender erythemato-violaceous, slightly scaly, flattopped plaques, distributed over her forehead [Figure 1], left cheek, right oral commissure and back [Figure 2]. Palms, soles, oral and genital mucosa were all free of lesions. There was no enlargement of lymph nodes, liver or spleen and the remaining physical examination was normal. Routine blood tests revealed an erythrocyte sedimentation rate of 84 mm at the end of one hour. Serological tests were negative for syphilis, hepatitis B and C and human immunodeficiency virus (HIV). Skin biopsy showed hyperkeratosis, focal parakeratosis and irregular acanthosis of the epidermis. There was a dense cellular infiltrate, grossly nodular, in the entire dermis [Figure 3],[Figure 4]. The results of the periodic acid-Schiff, Ziehl-Neelsen and Warthin-Starry stains were all negative. Cell-marker studies showed a heterogeneous population of cells without any phenotypic changes.

Migration of the Epidermal over the Dermal Component (Epiboly) in a Bilayered Bioengineered Skin Construct

A bilayered bioengineered living skin construct (LSC) consisting of viable human neonatal keratinocytes over a collagenous dermis seeded with dermal fibroblasts has been used extensively in difficult—to heal human wounds. Its biological properties include production of several mediators, cytokines, and growth factors and the ability to heal itself upon injury. In this study, we investigated the process of keratinocyte migration in LSC. At baseline, 6-mm punch biopsies of the construct were placed in serum-free medium (AIM-V) or Dulbecco's modified Eagle medium. At varying time points, the LSC samples were processed and analyzed using histology and immunohistochemistry. By 72 h, in a time-dependent manner, the overlying epidermis had migrated over and enveloped the entire underlying dermis, a process known as epiboly. Increasing concentrations of neutralizing antibodies to epidermal growth factor or interleukin-1 alpha down-regulated the extent of epiboly, as measured using computerized planimetry, but antibodies to transforming growth factor-beta 1 did not affect it. The consistent expression of laminin V, α3β1 integrin, and vitronectin (epibolin) and its integrin receptor (αvβ5) characterized the tongue of migrating epidermis. Increasing concentrations of antibodies to vitronectin blocked the process of epiboly, as did antibodies to the αvβ5 integrin receptor, which mediates vitronectin-driven keratinocyte locomotion. This process of epiboly provides novel mechanisms of action for bioengineered skin constructs.

Migration of the Epidermal over the Dermal Component (Epiboly) in a Bilayered Bioengineered Skin Construct

A bilayered bioengineered living skin construct (LSC) consisting of viable human neonatal keratinocytes over a collagenous dermis seeded with dermal fibroblasts has been used extensively in difficult-to heal human wounds. Its biological properties include production of several mediators, cytokines, and growth factors and the ability to heal itself upon injury. In this study, we investigated the process of keratinocyte migration in LSC. At baseline, 6-mm punch biopsies of the construct were placed in serum-free medium (AIM-V) or Dulbecco's modified Eagle medium. At varying time points, the LSC samples were processed and analyzed using histology and immunohistochemistry. By 72 h, in a time-dependent manner, the overlying epidermis had migrated over and enveloped the entire underlying dermis, a process known as epiboly. Increasing concentrations of neutralizing antibodies to epidermal growth factor or interleukin-1 alpha down-regulated the extent of epiboly, as measured using computerized planimetry, but antibodies to transforming growth factor-beta 1 did not affect it. The consistent expression of laminin V, alpha3beta1 integrin, and vitronectin (epibolin) and its integrin receptor (alphavbeta5) characterized the tongue of migrating epidermis. Increasing concentrations of antibodies to vitronectin blocked the process of epiboly, as did antibodies to the alphavbeta5 integrin receptor, which mediates vitronectin-driven keratinocyte locomotion. This process of epiboly provides novel mechanisms of action for bioengineered skin constructs.

Treatment of Facial Angiofibroma of Tuberous Sclerosis Using Cultured Epithelial Autografts

Treatment of facial angiofibroma of tuberous sclerosis is problematic, because the skin lesions involve entire dermis. Five patients aged from 14 to 33 (mean: 23.6) years old with angiofibroma of tuberous sclerosis were treated with cultured epithelial autografts between 1995 and 2004. The entire area of the facial lesions was excised using a razor to remove large nodules, and then the remaining lesions were further abraded to a rather deep layer of the dermis to smooth the skin and remove small nodules. Then a cultured autologous epithelium was grafted onto the wound. In all patients, epithelization was complete within 10 (mean: 9) days after the surgery. All patients were followed up for more than 6 months and showed neither depigmentation due to scar formation nor hypertrophic scars. In some patients, some pebbly regrowth had occurred at 5 years postoperatively, but the appearance was quite acceptable.

Verrucous Hemangioma Revisited

We analyzed the clinical and histopathologic characteristics of verrucous hemangioma, compared these findings to hyperkeratotic mimickers such as capillary-lymphatic malformation or capillary-venous malformation and angiokeratoma circumscriptum, and reconsidered whether the term verrucous hemangioma is appropriate in the current nosology of vascular anomalies. Fourteen similar-appearing localized hyperkeratotic vascular lesions were identified by one surgeon as either angiokeratoma, angiokeratoma circumscriptum, capillary-venous malformation, capillary-lymphatic malformation, or verrucous hemangioma. All lesions were located on an extremity, except for one lesion on the trunk, and were single or grouped and 2.6 to 8 cm in diameter. All were raised, red-to-purple, variably keratotic with irregular borders, and several manifested intermittent bleeding and oozing. Excision was performed at 4 months to 16 years of age. After histologic review, three lesions were designated as combined vascular malformations composed of capillaries, lymphatics, and veins, and none was designated as angiokeratoma. Eleven of 14 specimens met the histologic criteria for verrucous hemangioma: a hyperkeratotic epidermis with small, thick-walled, blood-filled vessels with multilamellated basement membrane involving the entire dermis as well as the subcutis. Immunostaining showed focal GLUT1 endothelial positivity (7/11) and low-level MIB-1 reactivity (8/11). Verrucous hemangioma has the accepted clinical features of vascular malformation, specifically presence at birth and proportionate growth. Microscopic features, such as thick vascular walls, multilamellated basement membrane, relatively uniform channel size, and GLUT1 immunopositivity are reminiscent of infantile hemangioma, particularly in its involutive phase. No firm conclusion seems possible as to whether verrucous hemangioma is a malformation or an indolent tumor, but clinical evidence favors the former category.