Essential thrombocythemia manifesting as livedoid and purpuric skin lesions: Report of two cases and literature review.

Essential thrombocythemia is a chronic myeloproliferative syndrome which usually runs its course as an asymptomatic elevated platelet count. Cutaneous manifestations secondary to microcirculation abnormalities are rare but can represent a helpful diagnostic clue in order to prevent major thromboembolic events. We report two cases of heterogeneous livedoid and "net-like" skin lesions in the context of essential thrombocythemia with identical histopathologic findings (medium-sized blood vessels with luminal obliteration by eosinophilic material, mostly positive for the platelet marker CD61, without vasculitis). In conclusion, we seek to raise awareness of the clinicopathological features of essential thrombocythemia to allow for prompt diagnosis and treatment.

The importance of total-body photography and sequential digital dermatoscopy for monitoring patients at increased melanoma risk.

BACKGROUND AND OBJECTIVES: The incidence of melanoma is rising and prevention plays an important role. Multiple nevi as well as a medical history of melanoma are important risk factors. In affected patients, a two-step algorithm consisting of total-body photography (TBP) and sequential digital dermatoscopy (SDD) is a helpful diagnostic tool. PATIENTS AND METHODS: This was a retrospective observational study that lasted six years in order to evaluate the significance of the two-step algorithm. Cases were evaluated based on distinct dermoscopic patterns and statistical analyses were performed with the latest version of SPSS. RESULTS: 6020 dermoscopic images of 214 patients were included. TBP was performed at a mean interval of 16.9 months (SD ± 1.43 months), while SDD was performed every 9.9 months (SD ± 1.68 months). The number needed to excise was 4.6 and the number needed to monitor was 548. Excisions were mostly performed because dynamic changes were observed. A total of eleven melanomas were detected and had a mean tumor thickness of 0.44 mm (SD ± 0.15 mm; range 0.2-0.6 mm). CONCLUSIONS: Invasive melanomas had a tumor thickness of less than 0.6 mm, thus providing evidence of an effective strategy for early melanoma detection. Excisions of benign nevi were minimized as indicated by a low number needed to excise.

Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies.

Axonal polyneuropathies are a frequent cause of progressive disability in the elderly. Common etiologies comprise diabetes mellitus, paraproteinaemia, and inflammatory disorders, but often the underlying causes remain elusive. Late-onset axonal Charcot-Marie-Tooth neuropathy (CMT2) is an autosomal-dominantly inherited condition that manifests in the second half of life and is genetically largely unexplained. We assumed age-dependent penetrance of mutations in a so far unknown gene causing late-onset CMT2. We screened 51 index case subjects with late-onset CMT2 for mutations by whole-exome (WES) and Sanger sequencing and subsequently queried WES repositories for further case subjects carrying mutations in the identified candidate gene. We studied nerve pathology and tissue levels and function of the abnormal protein in order to explore consequences of the mutations. Altogether, we observed heterozygous rare loss-of-function and missense mutations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. We also found that MME mutations resulted in strongly decreased tissue availability of neprilysin and impaired enzymatic activity. Although neprilysin is known to degrade ß-amyloid, we observed no increased amyloid deposition or increased incidence of dementia in individuals with MME mutations. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment.

Atypical clinical presentation of primary and secondary cutaneous follicle center lymphoma (FCL) on the head characterized by macular lesions.

BACKGROUND: Primary cutaneous follicle center lymphoma (pcFCL) usually presents with reddish nodules, plaques, and tumors on the head and neck or the back. OBJECTIVE: We sought to describe a peculiar clinical presentation of pcFCL and secondary cutaneous follicle center lymphoma (FCL). METHODS: We report a series of 13 patients (7 male and 6 female; median age 58 years, mean age 58.2 years, age range 26-83 years) with either pcFCL (11 patients) or secondary cutaneous FCL (2 patients) presenting with lesions on the head deviating from the classic clinical manifestations characterized by plaques and tumors. RESULTS: All patients presented clinically with diffuse, ill-defined, partly hypochromic, partly erythematous macules or with inconspicuous lesions located predominantly on the scalp and forehead. Dimension ranged between 4 to 5 cm2 and greater than 30 cm2. The initial diagnosis was never cutaneous lymphoma, and all patients received various diagnoses including rosacea, alopecia, erysipelas, discoid lupus erythematosus, angiosarcoma, Borrelia infection, or sarcoidosis. Histologic examination confirmed the diagnosis of FCL in all patients. LIMITATIONS: Small number of cases and retrospective study design are limitations. CONCLUSIONS: This clinical presentation of both pcFCL and secondary cutaneous FCL is unusual and represents a pitfall in the clinical diagnosis. Dermatologists should be aware of this clinical variant of FCL to establish a timely diagnosis and treat patients properly.

Phenotypic Variation in Different Lesions of Mycosis Fungoides Biopsied Within a Short Period of Time From the Same Patient.

Phenotypic variants of mycosis fungoides (MF) include mainly the expression of cytotoxic markers by neoplastic cells (either α/ß or γ/δ cytotoxic). To manage the patient properly, distinction from other cutaneous cytotoxic natural killer/T-cell lymphomas is paramount. Particularly for cutaneous γ/δ T-cell lymphoma, distinction is often based on clinicopathologic correlation (presence of tumors at first diagnosis as opposed to patches only in MF). The authors report a case of cytotoxic MF characterized by expression of TCRγ in two of three biopsies performed within a time frame of 1 week. The patient presented with patches, plaques, and 1 tumor at the time of first diagnosis; thus, distinction from cutaneous γ/δ T-cell lymphoma was not possible on clinical grounds alone. The diagnosis of MF was established, thanks to the phenotypic variations revealed by the three biopsies, with 1 lacking expression of cytotoxic proteins (TIA-1 and granzyme B) and of TCRγ. This case shows the importance to perform several biopsies in cases of cutaneous lymphoma, as morphologic and phenotypic features are variable and information gathered from a single biopsy may result in a wrong diagnosis.

Spiritual well-being and coping in scleroderma, lupus erythematosus, and melanoma.

BACKGROUND AND OBJECTIVES: Religious/spiritual (R-S) well-being is associated with greater vitality and lower depression scores. In this study, we investigated strategies for coping with disease and the role of religiosity/spirituality with respect to improving subjective well-being. PATIENTS AND METHODS: One hundred and forty-nine patients (107 women), 44 of whom with systemic sclerosis (SSc), 48 with lupus erythematosus (LE), and 57 with stage I or II malignant melanoma (MM) were surveyed using a self-designed questionnaire, which addressed subjective well-being and disease-related circumstances, as well as the Multidimensional Inventory for Religious/Spiritual Well-Being (MI-RSWB). RESULTS: At the time of diagnosis, disease burden is greater in LE patients than in patients with SSc and MM. Only after several years are SSc and LE patients able to accept their disease. Compared with healthy individuals, the overall score of R-S well-being is significantly lower in LE patients. In LE, photosensitivity and joint pain are inversely correlated with the ability to forgive. SSc patients with facial lesions and pulmonary involvement show greater religiosity. MM patients display significantly higher values for transcendental hope. CONCLUSION: Talks about the disease and psychological support are the most important needs of patients with SSc, LE, and MM. At present, programs aimed at improving R-S coping skills do not seem to play a significant role, but could be an important resource that should be addressed in the future.

Spirituelles Wohlbefinden und Coping bei Sklerodermie, Lupus erythematodes und malignem Melanom.

HINTERGRUND UND ZIELE: Religiös-spirituelles Wohlbefinden ist verbunden mit höherer Vitalität und verminderter Depressionsneigung. In unserer Studie untersuchten wir die Strategien zur Krankheitsbewältigung und die Rolle von Religiosität-Spiritualität (R-S) zur Verbesserung des subjektiven Wohlbefindens. PATIENTEN UND METHODIK: 149 Patienten (107 Frauen), 44 mit systemischer Sklerodermie (SKL), 48 mit Lupus erythematodes (LE) und 57 mit malignem Melanom (MM), Stadium I-II, wurden mittels eines selbstentwickelten Fragebogens zum subjektiven Wohlbefinden, zu den mit der Erkrankung einhergehenden Umständen sowie mit dem Multidimensionalen Inventar (MI-RSB) zu R-S befragt. ERGEBNISSE: LE-Patienten sind zum Zeitpunkt der Diagnosestellung stärker belastet als SKL- und MM-Patienten. SKL- und LE-Patienten können erst nach Jahren die Erkrankung akzeptieren. Der Gesamtscore des religiös-spirituellen Befindens liegt bei LE-Patienten signifikant unter dem Wert der Normalbevölkerung. Fotosensitivität und Gelenksschmerzen sind bei LE-Patienten negativ assoziiert mit der Fähigkeit Vergeben zu können. SKL-Patienten mit Gesichtsveränderungen und Lungenbeteiligung zeigen höhere allgemeine Religiosität. MM-Patienten haben höhere Werte für transzendente Hoffnung. SCHLUSSFOLGERUNGEN: Vorträge über die Krankheit und psychologische Betreuung sind die wichtigsten Bedürfnisse von Patienten mit SKL, LE und MM an ihre Betreuer. Religiös-spirituelle Angebote zur Krankheitsverarbeitung scheinen derzeit eine untergeordnete Rolle zu spielen, könnten aber eine wichtige Ressource sein, der man in Zukunft mehr Aufmerksamkeit schenken sollte.

Atypical clinicopathologic presentation of primary cutaneous diffuse large B-cell lymphoma, leg type.

BACKGROUND: Primary cutaneous diffuse large B-cell lymphoma, leg type (cDLBCL-LT) is a well-defined entity of cutaneous B-cell lymphoma affecting predominantly elderly patients, mostly women. The typical clinical presentation is characterized by solitary or multiple, rapidly growing plaques or tumors on 1 leg (rarely both legs). OBJECTIVE: We sought to describe a new clinical variant of cDLBCL-LT that deviates from the conventional one. METHODS: Clinical, histopathologic, phenotypical, and molecular features of 3 cases of cDLBCL-LT presenting with patches or thin plaques were reviewed (all were women, aged 60, 62, and 87 years; lesions were located on the leg in all patients). RESULTS: These patients presented with patches or thin plaques that represented the first manifestation of cDLBCL-LT. All 3 patients reported a history of long-standing lesions (present for 6, 9, and 18 months, respectively). Histology revealed moderately dense, perivascular infiltrates of small lymphocytes admixed with variable numbers of large cells that were CD20(+), Bcl-2(+), and MUM-1(+). LIMITATIONS: There were only a small number of cases. CONCLUSIONS: We reported an unusual clinical presentation of cDLBCL-LT that deviates from the conventional one and that represents a formidable diagnostic challenge. Biopsy specimens of unusual patches/thin plaques or annular lesions should be obtained from the legs of adult patients if the lesions do not respond to conventional treatment.

Bullous melanoma: a rare variant of melanoma causing practical problems in determination of tumor thickness.

Bullous melanoma represents a rare variant of melanoma characterized by variably large subepidermal, basilar, or suprabasilar blisters. We present 7 cases of bullous melanoma (M:F = 4:3; median age, 57 years; age range, 38-86) located on the heel (n = 2), foot (n = 2), arm (n = 2), and back (n = 1). In 5/7 cases, the bulla was due to dyscohesiveness of basilar or suprabasilar melanocytes with subsequent acantholytic features simulating pemphigus vulgaris or Hailey-Hailey disease, whereas in the last 2 cases a subepidermal bulla without clear-cut relation to the melanocytic complexes was observed. Direct and indirect immunfluorescence studies performed in 4 patients on skin near the original surgical scar (including those with subepidermal bullae) were negative. Measurement of the Breslow index in all 7 cases was affected by the presence of the bulla, and in 5 of them, the TNM classification was different depending on the method of measurement (with or without the bulla). We suggest that the Breslow index in these cases should be measured detracting the thickness of the bulla from the total thickness, but follow-up data on larger numbers of patients are necessary to establish whether the presence of bullous features has any prognostic implication.

Dermoscopy, reflectance confocal microscopy and immunohistochemical analysis in melanocytic lesions with Meyerson's phenomenon.

BACKGROUND: Meyerson's phenomenon is characterized by a symmetrical halo of erythema and scale around central, mostly melanocytic lesions. OBJECTIVE: Our aim was to describe the dermoscopic and reflectance confocal microscopy (RCM) features of melanocytic tumors less frequently associated with Meyerson's phenomenon, with histopathology and immunohistochemistry correlation. METHODS: Clinical, dermoscopic and RCM images of 4 histopathologically confirmed melanocytic tumors associated with Meyerson's phenomenon (3 dysplastic compound nevi and 1 melanoma) were retrospectively collected, with additional immunohistochemical analysis. RESULTS: RCM showed in vivo features of both melanocytic and spongiotic nature of the lesion associated with Meyerson's phenomenon, even in cases with absent halo. Our study also supported the involvement of immune-mediated CD4+ T lymphocyte mechanisms and Langerhans cells. CONCLUSION: Our case series supports the potential of RCM in the evaluation of tumoral and inflammatory skin diseases. RCM features of rare Meyerson's melanoma were also described for the first time. © 2014 S. Karger AG, Basel.

Alopecia universalis associated with cutaneous T cell lymphoma.

BACKGROUND: Alopecia areata-like hair loss may occur in the context of cutaneous T cell lymphoma (CTCL) and can very rarely evolve to alopecia universalis-like presentation. The dermoscopic findings of CTCL-related alopecia have not been described. METHODS: Two patients with alopecia areata universalis-like hair loss occurring in the context of preexisting, pathology-proven CTCL are presented. RESULTS: Clinical examination showed subtotal scalp alopecia with sparse fine hair or total scalp alopecia with loss of eyebrows, eyelashes and body hair. On dermoscopy there was follicular or diffuse scaling, reduced number of follicular openings with broken hairs, short hairs or keratotic filiform spicules. Pathology confirmed the diagnosis of CTCL-related alopecia. One patient had almost complete hair regrowth after treatment. CONCLUSION: CTCL-related alopecia universalis is a rare non-scarring form of hair loss which simulates alopecia areata universalis. We provide clues to distinguish both based on clinical, dermoscopic and pathologic findings.