Extended surgical safety margins and ulceration are associated with an improved prognosis in pleomorphic dermal sarcomas.

BACKGROUND: Pleomorphic dermal sarcomas (PDS) are frequent UV-induced sarcomas of the skin of intermediate grade malignant potential. Despite the fact that PDS have a noteworthy potential to recur (up to 28%) as well as to metastasize (up to 20%), there are no specific clinical guidelines with respect to follow-up these patients. Moreover, little is known about clinical, histological or molecular prognostic factors in PDS. OBJECTIVE: The aim of the present study was to identify risk factors to predict relapse in a large multicentre sample cohort of PDS which could aid to optimize personalized treatment recommendations regarding surgical safety margins and adjuvant radiotherapy. METHODS: Patients with a diagnosis of PDS were selected from nine European institutions based on the histopathologic criteria described by Fletcher. Clinicopathologic and follow-up data were collected and statistically analysed calculating univariate hazard ratios with 95% confidence intervals by use of the Cox proportional-hazards model and a significance level of P < 0.05. Patients with an incomplete excision of the tumour were excluded. RESULTS: Univariate Cox regression analysis of possible prognostic factors for progression-free survival (PFS) performed in 92 patients revealed that an excision margin of <2 cm is significantly associated with relapse of PDS [hazard ratio 4.478 (95% CI 1.536-13.055), P = 0.006]. Ulceration of the tumour was associated with a significantly better prognosis [0.396 (0.174-0.904), P = 0.028] whereas adjuvant radiotherapy did not reach statistical significance to improve prognosis in patients with PDS [0.775 (0.231-2.593), P = 0.679]. Gender, age, immunosuppression, intratumoural necrosis, tumour location, vertical thickness or horizontal diameter did not significantly influence PFS in PDS. CONCLUSION: We identified surgical safety margins of <2 cm and absence of ulceration as risk factors for relapse in patients with PDS. These findings may be implemented into both the primary treatment as well as the further monitoring of patients with PDS.

[Keep an eye on the side effects]. / Nebenwirkungen im Auge behalten.

A 52-year-old man presented with a progressive grey-black pigmentation of facial skin, sclera and teeth. The cause was long-term ingestion of minocycline, as confirmed by history and skin biopsy. Minocycline-induced hyperpigmentation can be divided into four main patterns based on clinical appearance, distribution, light- and electron microscopic characteristics. Some patterns can manifest within weeks of initiating therapy. One must be alert to the early signs and warn the patient about the often cosmetically disturbing and persistent minocycline-induced hyperpigmentation.

[Granulomatous mycosis fungoides: combination therapy with bexarotene and PUVA]. / Granulomatöse Mycosis fungoides : Kombinationstherapie mit Bexaroten und PUVA.

A 74-year-old male with granulomatous mycosis fungoides presented with multiple, red-brown macules and plaques up to 8 cm in diameter, just as in classical mycosis fungoides. Dermatohistopathologic findings showed extensive granulomatous infiltrates, in which clonality could be detected in various locations via T cell receptor rearrangement. Granulomatous mycosis fungoides is a very rare form of mycosis fungoides with histological resemblance to granulomatous slack skin. It shows a rather aggressive course and can be challenging to diagnose. In our case, combination treatment with bexarotene and bath PUVA, as recommended in guidelines, resulted in an impressive improvement of the skin lesions within ten weeks.

[Nodular granuloma of the lip. An unusual manifestation of secondary syphilis]. / Epitheloidzellige granulomatöse Entzündungsreaktion an der Lippe. Ungewöhnliche Manifestation im Stadium II bei Frühsyphilis.

Syphilis is a sexually transmitted disease caused by Treponema pallidum which evolves through three overlapping stages. A 50-year-old woman presented with an expanding painless granulomatous nodule on her lower lip in combination with a maculo-papular exanthem. Both serologic studies and microscopic examination indicated an infection with Treponema pallidum. This case shows an unusual granulomatous nodular presentation of syphilis on the lower lip, emphasizing the variable clinical and histological manifestations syphilis, which shows an increasing number of new infections worldwide in recent years.

[Segmental type 1 manifestation of Darier disease. An example of cutaneous mosaicism]. / Segmentale Typ-1-Manifestation des Morbus Darier. Ein kutanes Mosaik.

A 45-year old man presented with red-brown hyperkeratotic papules that were distributed in an unilateral segmental fashion on the right thorax. Histopathological examination revealed acanthosis and, in particular, acantholysis and dyskeratosis in the basal and suprabasal epidermal layers. Based on the clinical and histopathologic findings we diagnosed a type 1 segmental Darier disease. Darier disease is an autosomal dominant disorder that is caused by mutations in the ATP2A2 gene and is characterized by dysfunctional adhesion between neighboring keratinocytes. The type 1 segmental manifestation reflects a de novo postzygotic somatic mutation in the heterozygous state and as a rule can be found in all autosomal dominantly inherited genodermatoses.

[Eruptive melanocytic nevi during azathioprine therapy in myasthenia gravis]. / Eruptive melanozytäre Nävi unter Behandlung einer Myasthenia gravis mit Azathioprin.

While being treated with azathioprine and dexamethasone, a 21-year old man with myasthenia gravis suddenly developed rapidly progressing brown macules, predominantly on the trunk, palms and soles. We made a diagnosis of eruptive melanocytic nevi (EMN). This rare entity can appear after blistering skin diseases, in immunocompromised patients, and, in particular, during immunosuppressive therapy for autoimmune diseases. Since therapeutic regimens including azathioprine have been frequently reported in association with EMN, we recommended to our patient a treatment switch to mycophenolic acid to prevent the development of more nevi.

[NK/T-cell lymphoma, nasal type with cutaneous dissemination]. / NK/T-Zell-Lymphom vom nasalen Typ mit kutaner Dissemination.

Extranodal NK/T-cell lymphoma, nasal type, is a lymphoproliferative disorder originating from peripheral T-cells or natural killer (NK) cells. While it is a rare disease in Europe, it is more frequent in Asia and South America. It is associated with Epstein-Barr virus (EBV) infection and characterized by an extremely aggressive course and poor prognosis. We report a 46-year-old Caucasian woman who presented with multiple subcutaneous, painful nodules on the trunk first noticed a few weeks earlier. In addition to dermatological findings, the patient reported a 4-months history of necrotizing nasopharyngeal inflammation of unclear origin. Due to nonspecific histological and clinical findings mimicking a chronic inflammatory condition, a diagnosis of Wegener disease was made and immunosuppressive therapy with azathioprine was initiated. However the disease progressed under therapy. Histopathological reevaluation and immunophenotyping revealed a disseminated NK/T-cell lymphoma, nasal type. In the case of an unspecific chronic inflammatory process in the nasopharyngeal space one should always consider the possibility of this rare lymphoma, even in Europe.

[Hereditary cutaneous leiomyomatosis]. / Hereditäre kutane Leiomyomatose.

The occurrence of multiple cutaneous leiomyomas can be indicative of hereditary cutaneous leiomyomatosis. This autosomal dominant disorder is due to germline mutations in the fumarate hydratase (FH) gene. Associations with uterine myomas and renal cell carcinomas have been described and are referred to as Multiple Cutaneous and Uterine Leiomyomas (MCUL) or Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC), respectively. A 34-year-old man presented with multiple red-brown papules and nodules. After histopathologic confirmation of piloleiomyomas, we made the diagnosis of hereditary cutaneous leiomyomatosis. Taking into consideration the aforementioned complications, close interdisciplinary management of these patients and regular screening examinations within affected families are mandatory.

Epidermal and dermal changes in response to various skin rejuvenation methods.

During the last years, a number of new devices have been developed to improve the dermal and epidermal signs of photo- and chronological skin ageing. There are well-established ablative and non-ablative skin resurfacing options using different lasers and light sources, but side effects have been observed frequently. A recently developed photorejuvenation method using non-thermal stimulation of skin cells with low energy and narrow band light has been termed photomodulation. Light emitting diodes are the ideal source of this kind of light that stimulate mitochondrial cell organelles leading to up-regulation of cytochrome electron transport pathway leading to mitochondrial DNA gene modulation. This paper reviews the most current knowledge of intrinsic and extrinsic changes of ageing and summarizes different systems for skin rejuvenation with focus on non-thermal non-ablative skin rejuvenation modalities.

[Desmoplastic fibroma on arm of 22-year-old woman]. / Desmoplastisches Fibroblastom bei einer 22-jährigen Patientin im Bereich des Oberarms.

Desmoplastic fibroblastoma ("collagenous fibroma") is a rare benign, slowly progressive fibrous soft tissue tumor that ranges 1-20 cm in size. The tumor occurs in all ages, predominantly in the upper part of the body. Children are rarely affected. The tumor often infiltrates the subcutis; less often it invades the fascia and skeletal muscle or causes bone erosions. Histologically, the tumor is composed of spindle-shaped cells embedded in a densely collagenous stroma, sometimes forming a pseudo-capsule. Magnetic resonance imaging and computed tomography as well as ultrasonography are used to define the extensions of the tumor. Because it is clinically extremely difficult to determine if soft tissue tumors are benign or malignant, all should be excised with a margin of safety and examined histologically. We report a 22-year old woman with desmoplastic fibroblastoma located on the upper arm. Clinical and histopathological findings and treatment options are discussed.

[Brownish plaques on both sides of the nose]. / Bräunliche Plaques an beiden Nasenseiten.

Granuloma fissuratum (Gf) is painful granular tissue caused by constant pressure exerted by glasses. The differential diagnosis includes further granulomatous dermatoses such as cutaneous sarcoidosis, mycobacterioses and autoimmune diseases. It is also important to rule out a basal cell carcinoma. The simplest and most effective treatment of Gf is to correct the glasses frame or, even better, to avoid wearing glasses to correct eyesight. Topical antiseptic/antibiotic treatment is recommended for superinfected lesions. The Gf usually heals within 1-6 months after correction of the glasses. If the lesion does not heal on its own, complete excision is recommended.

[Keratosis follicularis spinulosa decalvans]. / Keratosis follicularis spinulosa decalvans.

Keratosis follicularis spinulosa decalvans is a rare, X-linked disorder of keratinization of the hair follicle with inflammation and atrophy associated with corneal dystrophy and other symptoms. A family with several affected members is reported. The unaffected parents were related. A 12-year-old girl and her 5-year-old brother had follicular spiny hyperkeratoses on the trunk and extremities. The girl had thinning of the eyelashes and eyebrows as well as scarring alopecia of the scalp as additional features of the disease. Both the girl and her brother had corneal dystrophy and photophobia. Two sisters aged 8 and 10 years did not show similar skin or eye findings.

Does creatinine adjustment of urinary pregnanediol glucuronide reduce or introduce measurement error?

Correlation between urinary pregnanediol and serum progesterone measurements and the influence of age, race, smoking and urinary creatinine adjustment was determined during the luteal phase of the menstrual cycle in 175 volunteers. A decline in serum progesterone was observed with increasing age. Mean baseline urinary creatinine declined with increasing age in non-smokers and was not affected by race or baseline weight. An excellent correlation between urinary pregnanediol glucuronide and serum progesterone levels existed except when urinary pregnanediol concentrations were adjusted using creatinine measurements in older individuals. Adjustment of urinary pregnanediol glucuronide concentration using creatinine measurement is therefore discouraged.

Predictors of ovarian steroid secretion in reproductive-age women.

During the baseline period (1985-1988) of a prospective study, midcycle and luteal-phase estrogens and progestins were measured in 175 healthy women aged 21-36 years with spontaneous, cyclic menses in Brooklyn, New York. Subjects contributed daily first-morning urine specimens and three blood specimens during a single menstrual cycle monitored by basal body temperature. Hormone levels were compared according to age, race, and levels of known or suspected breast cancer risk factors. Late age at menarche was associated with increased urinary and serum progestin levels. Increased body weight was associated with decreased progestin levels, even in ovulatory women. Neither weight nor age at menarche was related to estrogen levels. Cigarette smoking was associated with decreased midcycle and luteal-phase estradiol levels. No other factors were associated with differences in any of the hormones measured either midcycle or during the luteal phase, despite good statistical power to detect moderate differences. Sources of individual variability in ovarian steroid levels remain unexplained. These data do not support hypotheses that breast cancer risk factors act through an effect on ovarian hormones during the middle reproductive years.

Regeneration of adsorbed and covalently immobilized antibodies on solid phases for immunoassay.

A technique for the reproducible re-use of antibody-coated solid phases for immunoassays is described. The method based on the dissociation of the antigen-antibody complexes. Two different procedures, using glycine buffer (pH 2.3) or ethanolamine, were developed. More than ten immunoassay cycles can be realized with the same antibody-coated microtitre plates. These procedures were tested with competitive and sandwich immunoassays, monoclonal and polyclonal antibodies, and a commercial immunoassay kit.