Dysplastic melanocytic nevi of the lower leg: sex- and site-specific histopathology.

Site-specific histopathology features have been reported for acral, auricular, flexural, and genital melanocytic nevi, however, to the best of our knowledge, site- and sex-specific histology of dysplastic nevi on the lower leg (between knee and ankle) of women (DN-LW) has not been reported. In this retrospective histopathology study, we compared DN-LW (N = 42) with appropriate control groups of (1) DN of the lower leg of men (N = 20; DN-LM), (2) DN from the back of women (N = 20), (3) common nevi of the lower leg of women (N = 40), and (4) levels 1-2 superficial spreading melanoma of the lower leg of women (N = 20). Compared with dysplastic nevi on the back, DN-LW were smaller in diameter and exhibited a significantly higher score for pagetoid spread (P < 0.05). DN-LW compared with DN-LM showed sex-specific differences with (1) pagetoid spread (P < 0.05), (2) cytologic atypia (P < 0.05), (3) presence of large melanocytes (P < 0.05), and (4) band-like pigmentation in the dermis underlying the nevus (54% in DN-LW vs. 15% in DN-LM). As with other body sites, the dermatopathologist should be aware that dysplastic nevi occurring on the lower leg in women have site- and sex-specific features. Knowing this profile may lower the risk of misdiagnosing DN-LW and melanoma of the lower leg of women.

Ultrastructural evidence of dermal gadolinium deposits in a patient with nephrogenic systemic fibrosis and end-stage renal disease.

BACKGROUND AND OBJECTIVES: The pathogenesis of acquired nephrogenic systemic fibrosis recently described for patients with renal insufficiency and a history of exposition to gadolinium-based magnetic resonance contrast agents is not completely understood. A role for circulating fibroblasts in the fibrosing tissue is hypothetical, and the mechanism of the assumed trigger function of gadolinium remains elusive. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A skin lesion on a 76-yr-old man with symptoms of nephrogenic systemic fibrosis lasting 5 mo was studied at the ultrastructural level. After confirmation of he diagnosis by histopathologic methods, the presence and distribution of gadolinium, iron, calcium, and magnesium by energy filtering transmission electron microscopy was also examined. RESULTS: The performed electron spectroscopic imaging and electron energy loss spectroscopic analyses on deparaffinized samples revealed deposition of gadolinium in irregular small aggregates that adhered to cell profiles and collagen fibers of the connective tissue, forming a perivascular "gadolinium-deposit zone" in the skin. Traces of iron signal were demonstrated in singular gadolinium-positive deposits, and iron presence was found in adjacent connective tissue. The ultrastructural cell analysis of the lesion showed among numerous poorly differentiated fibrocytes also higher differentiated cells with myofibroblastic characteristics, including bundles of intermediate filaments and attachment plaques in the cell periphery, indicating an ability of lesional fibroblasts to differentiate into myofibroblastic cells. CONCLUSIONS: These findings support the pivotal role of gadolinium chelates in the development of nephrogenic systemic fibrosis.

Targeted combined anti-inflammatory and angiostatic therapy in advanced melanoma: a randomized phase II trial.

An angiostatic approach was used to assess the impact of anti-inflammatory therapy in combination with metronomic low-dose chemotherapy. A randomized multi-institutional phase II trial was designed to select metronomic chemotherapy (arm A: trofosfamide 50 mg orally three times daily, day 1+) or combined anti-inflammatory/angiostatic treatment (arm B: trofosfamide as above mentioned plus rofecoxib 25 mg orally, day 1+, and pioglitazone 60 mg orally, day 1+) for further evaluation. A total of 76 patients, mostly (>60%) refractory to at least one previous chemotherapy with maximum tolerated doses, and progression of metastatic melanoma were included. The estimated progression-free survival (PFS) rates at one year were 0% for metronomic chemotherapy (A), but 9% for additional anti-inflammatory therapy (B). Vice versa the hazard ratio for the intent-to-treat analysis of A versus B was 1.9 (P=0.008). By Cox analysis, the impact of anti-inflammatory therapy on PFS achieved significance (P=0.016) as well as C-reactive protein response on overall survival (P=0.045). WHO grade 3 (no grade 4) toxicities were reported in arm A/B in 19 and 28%, respectively. In conclusion, control of tumour-associated inflammatory processes (C-reactive protein response) is associated with longer PFS than achieved with metronomic chemotherapy alone in metastatic melanoma.

PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas.

Trichoblastomas are rare, benign tumors of the appendix in human skin. The histopathology comprises elements of basal cell carcinoma and trichoepithelioma with a variable degree of follicular differentiation. Both basal cell carcinoma and trichoepithelioma reveal alterations of PTCH, the human homolog of the Drosophila segment polarity patched gene. Furthermore, heterozygous PTCH knockout mice develop trichoblastoma-like tumors. This suggests an involvement of the PTCH gene in the pathogenesis of human trichoblastomas. However, trichoblastomas arising in nevus sebaceus did not show loss of heterozygosity at the PTCH locus (9q22.3) in a previous study. Sequencing of the PTCH gene and analysis of sporadic human trichoblastomas have not been performed yet. We therefore screened 10 sporadic trichoblastomas and 1 trichoblastoma arising within a nevus sebaceus for PTCH mutations. After microdissection of the tumors, single-strand conformational polymorphism (SSCP)/heteroduplex analysis of exons 2 to 23 of PTCH was performed, and polymerase chain reaction products with aberrant band patterns were sequenced. One trichoblastoma revealed a silent mutation at codon 562 in exon 12. Another trichoblastoma showed a somatic C > T single nucleotide substitution at codon 1,315 (exon 23), which was not present in corresponding normal epidermis. This mutation at codon 1,315 represents an already described PTCH germline polymorphism and results in a heterozygous Pro to Leu substitution in the tumor. The Pro/Leu polymorphism in germline is associated with a higher risk for breast cancer, but a potential contribution to the tumorigenesis of trichoblastoma is unknown. We detected no classical PTCH mutations in the investigated trichoblastomas. Our results indicate that PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas, in contrast to basal cell carcinomas and trichoepitheliomas. The genetic basis of this rare appendageal tumor remains elusive.

Rosai-Dorfman disease with cutaneous manifestation (sinus histiocytosis with massive lymphadenopathy).

We report a 73-year-old woman with the typical findings of "Rosai-Dorfman disease" (RDD) including massive, painless lymphadenopathy, fever and multiple, asymptomatic cutaneous lesions on her face, collum and neck. Histologically, the lesions were marked by characteristic large macrophages exhibiting emperipolesis.

Early recurrence of eruptive vellus hair cysts after Er:YAG laser therapy: case report and review of the literature.

BACKGROUND: Therapy of eruptive vellus hair cysts (EVHCs) often leads to unsatisfying results or recurrences. Recently, erbium:yttrium-aluminum-garnet (Er:YAG) laser therapy has been recommended in this condition. OBJECTIVE: To report the results of Er:YAG laser treatment and discuss the treatment options in EVHC, presenting a review of the literature. METHODS: Full-face Er:YAG laser therapy was performed in a 30-year-old female patient with a 15-year history of cosmetically bothersome facial EVHCs. RESULTS: Immediately after the laser treatment, the ablated skin showed an even surface, presenting no residual signs of EVHCs. After reepithelialization, however, early recurrence of EVHCs occurred. Recurrence was also observed in the previously treated test spot, where slight atrophy indicated deeper ablation. CONCLUSION: Er:YAG laser therapy might be a treatment option for distinct lesions of EVHCs but proved to be ineffective in a case of EVHCs in the face, where the depth of ablation is limited owing to the risk of atrophy or scarring and where deep enucleation of distinct single cysts was not possible owing to the dense dissemination of the lesions. Despite numerous treatment options reported in the literature, therapy for EVHCs is still challenging owing to recurrences or side effects.

Congenital cartilaginous rests of the neck (wattles).

BACKGROUND: Congenital cartilaginous rests of the neck (wattles) are very rare, probably branchiogenic malformations. OBJECTIVE: To discuss the clinical and histologic features and the therapy of wattles. METHODS: We report a 4-year-old patient with symmetric exophytic nodules of the neck that had been present since birth. RESULTS: The two lesions, 0.5 3 0.5 cm, were removed. The histopathologic examination confirmed ectopic cartilaginous tissue. CONCLUSION: Wattles must be excised, including their cartilaginous core, after having sonographically excluded fistulae or sinuses.

Fibroadenoma of the axilla.

BACKGROUND: Ectopic, axillary breast tissue can develop any disease that affects the normal breast, including fibroadenoma. OBJECTIVE: To report and discuss a case of fibroadenoma of the axilla in a 23-year-old woman. METHODS: Case report and discussion of the rare entity of fibroadenoma of the axilla. RESULTS: The histology was identical to the fibroadenomas seen in the breast and those observed along the milk line. CONCLUSION: Differential diagnosis of an axillary tumor should include ectopic breast tissue.

Comparison of two absorbable monofilament polydioxanone threads in intradermal buried sutures.

BACKGROUND AND OBJECTIVES: Two absorbable polydioxanone threads are compared regarding intraoperative handling qualities, scar dehiscence, and possible side effects. METHODS: In 30 excisions, half of each suture was performed with PDS II (Ethicon GmbH, Norderstedt, Germany), whereas the other half was closed with Serasynth (Serag-Wiessner, Naila, Germany). Clinical evaluation for scar spreading, spitting of the sutures, hypertrophic scarring, or suture granuloma was performed 3 and 6 months after surgery. RESULTS: No significant difference in scar spreading, hypertrophic scarring, or the incidence of suture granuloma was noted. A significantly lower frequency of spitting was seen with Serasynth than with PDS. The handling and suturing properties of SerasynthM were estimated to be slightly superior compared with those of PDS. CONCLUSION: Our study shows that PDS and Serasynth provide equal cosmetic results when applied in an appropriate suturing technique. Possibly owing to its better pliability, the frequency of spitting was lower with Serasynth.

Antiangiogenic therapy with pioglitazone, rofecoxib, and trofosfamide in a patient with endemic kaposi sarcoma.

BACKGROUND: Kaposi sarcoma (KS) in patients who are seronegative and seropositive for human immunodeficiency virus is currently the most common malignant tumor in central Africa. It accounts for 50% of all tumors reported in central African countries. Owing to the rising number of patients and the limitations of current therapies, there is an urgent demand for new strategies to treat KS. OBSERVATION: We describe a 42-year-old dark-skinned patient from Mozambique with endemic KS. The tumor was first diagnosed 8 years earlier when an ulcerated nodule appeared at his right ankle joint. Subsequently, multiple reddish brown nodules appeared on both feet and the left thigh. Results of dermatohistopathological analysis confirmed the diagnosis of KS. Topical therapies including cryotherapy, carbon-dioxide laser, and photodynamic therapy could not prevent new recurrences and further cutaneous dissemination. Therefore, a novel antiangiogenic systemic therapy was started that was previously shown to be effective in angiosarcomas other than KS. The regimen consists of the biomodulators pioglitazone hydrochloride and rofecoxib combined with a metronomic (daily) low-dose chemotherapy with trofosfamide. We observed a partial remission, which has been stable for 18 months. No significant toxic effects were observed. CONCLUSION: The suggested antiangiogenic strategy has the potential to become a cheap, practical, feasible alternative treatment for endemic KS, particularly suitable for the outpatient setting.

[The "red melanoma"--a rare form of amelanotic malignant melanoma]. / Das "rote Melanom"--eine seltene Variante des amelanotischen malignen Melanoms.

The two major variants of amelanotic malignant melanoma are the verrucous and the polypoid forms. A further--albeit rare--red eczematous variety has also been described. We report two female patients with reddish, non-pigmented, scaly lesions on the upper arm and the shoulder that had developed 2 to 3 years previously. One biopsy showed the diagnosis of a melanoma growing in situ while the second revealed a highly atypical melanocytic tumour. However, the histopathological examination of the entire tumour showed a superficial spreading amelanotic malignant melanoma. Therefore, in non-healing erythematous lesions, even without pigmentation or ulceration, the rare differential diagnosis of amelanotic malignant melanoma should be taken in consideration and a biopsy should be performed prior to therapy without histological control.

Spindle cell hemangioma.

BACKGROUND: Spindle cell hemangioma (SCH) is an uncommon benign vascular tumor. OBJECTIVE: To report and discuss a case of SCH in an 11-year-old boy. METHODS: A case report and discussion of the rare entity of SCH are given. RESULTS: The excision of a vascular tumor showed a vascular connection to the great saphenous vein. Histologic examination was consistent with SCH. CONCLUSION: The diagnosis of SCH is supported by typical histologic and immunohistochemical features and by the intraoperative finding of an association with a large vessel.

[Porokeratotic eccrine ostial and dermal duct naevus (PEODDN)]. / Porokeratotischer duktaler Naevus eccrinicus.

The porokeratotic eccrine ostial and dermal duct naevus or PEODDN represents a very rare hamartoma of the eccrine sweat glands. A 16-year old boy had developed subtle hyperkeratotic skin lesions on his right hallux at six months of age. When he was eight years old, he developed similar lesions on his right palm. Clinically the lesions were coniform hyperkeratoses. The histopathological examination confirmed the diagnosis of a PEODDN showing typical cornoid lamella where the eccrine secretory ducts penetrated the epidermis. Although porokeratotic eccrine ostial and dermal duct naevi are generally considered as unresponsive to conservative treatment, in our patient topical treatment with tazarotene gel 0.1% resulted in a significant improvement within three weeks.