-
Am J Dermatopathol. 01/2013; 2013 Jan 22. [Epub ahead of print].
-
[show abstract]
[hide abstract]
ABSTRACT: Bei einigen hereditären Tumorsyndromen existieren charakteristische Hauttumoren, deren Kenntnis und richtige Diagnose wegweisend
für eine möglichst frühzeitige Diagnosestellung der betroffenen Patienten und ihrer Familien sind. So ist das Muir-Torre-Syndrom
durch die Assoziation mit zystischen Sebazeomen typisiert und multiple Trichilemmome treten gehäuft bei einem zu Grunde liegenden
Cowden-Syndrom auf. Der Nachweis multipler oberflächlicher Angiomyxome sollte an einen Carney-Komplex denken lassen, während
multiple, perifollikuläre mesenchymale Tumoren hinweisend für das Birt-Hogg-Dubé-Syndrom sein können. Weitere Kombinationen
stellen multiple Angiofibrome und sog. Koenen-Tumoren bei der tuberösen Sklerose, multiple kutane Leiomyome und uterine Leiomyome
mit Nierenzellkarzinomen, das Gardner-Fibrom mit dem Gardner-Syndrom und multiple Basalzellkarzinome im jüngeren Lebensalter
mit dem Gorlin-Syndrom dar.
A number of hereditary tumor syndromes are associated with characteristic dermal neoplasms and knowledge and early diagnosis
of these lesions may facilitate the diagnostic of the underlying syndrome. These syndromes include Muir-Torre syndrome, associated
with cystic sebaceomas, Cowden syndrome, associated with multiple tricholemmomas, Carney complex associated with multiple
superficial angiomyxomas, Birt-Hogg-Dubé syndrome associated with multiple fibrofolliculomas, tuberous sclerosis associated
with multiple facial angiofibromas and so-called Koenen tumors, patients with renal cell cancer associated with pilar leiomyomatosis
and uterine leiomyomas, Gardner syndrome associated with Gardner fibromas and nevoid basal cell carcinoma associated with
multiple basal cell carcinomas in young patients.
SchlüsselwörterHereditäre Tumorsyndrome-Muir-Torre-Syndrom-Cowden-Syndrom-Carney-Komplex-Birt-Hogg-Dubé-Syndrom
KeywordsHereditary tumor syndrome-Muir-Torre syndrome-Cowden syndrome-Carney complex-Birt-Hogg-Dubé syndrome
Der Pathologe 04/2012; 31(6):489-496. · 0.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Die diffuse dermale Angiomatose (DDA) ist eine erworbene gutartige vaskuläre Neubildung mit schmerzhaften, unscharf begrenzten,
lividen, oft zentral exulzerierten Plaques, die an das Krankheitsbild der reaktiven Angioendotheliomatose oder der Embolia
cutis medicamentosa erinnern. Histologisch dominiert ein diffuses dermales Geflecht kapillärer, regulär strukturierter Gefäße.
Endotheliale Atypien, atypische Mitosen oder Vaskulitiszeichen fehlen. Es wird über eine 43-jährige Frau berichtet, die wenige
Tage nach operativer Entfernung einer Unterbauchfettschürze oberhalb der Operationsnarbe eine bizarre bräunlich livide, rasch
wachsende DDA entwickelte, die sich innerhalb von 12 Wochen ohne Residuen spontan zurückbildete. Bislang 4-jährige Rezidivfreiheit.
Diffuse dermal angiomatosis (DDA) is a benign, acquired vascular proliferation characterized by painful, poorly circumscribed,
livid-erythematous plaques with frequent central ulceration. The clinical features are reminiscent of reactive angioendotheliomatosis
or embolia cutis medicamentosa. Histologically, a dense diffuse network of regular capillary vessels throughout the dermis
is seen. Endothelial atypia, atypical mitoses or signs of vasculitis are missing. A 43-year-old woman developed a bizarre
brownish-livid rapidly growing lesion of DDA 8 centimeters above a surgical scar, shortly after removal of 20 kilograms of
fatty tissue from the lower abdominal wall. DDA regressed spontaneously within 12 weeks, and has not recurred over 4 years
of follow-up.
Der Hautarzt 04/2012; 53(12):808-812. · 0.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Postradiation cutaneous vascular lesions after treatment of breast carcinoma comprise a heterogeneous group of benign, atypical, and malignant lesions and are best regarded as points along a morphological spectrum. We analyzed a series of cutaneous angiosarcomas after treatment of breast cancer in comparison with control cases and cases of atypical vascular lesions with special emphasis on the expression and amplification of MYC. The 66 cases were divided into control cases (5), cases in which a slight vascular proliferation was seen after radiotherapy of breast cancer (12), cases of atypical vascular lesions after radiotherapy (16), cases of postradiation cutaneous angiosarcomas (25), and cases of angiosarcomas of skin and soft tissues unrelated to radiotherapy (8). None of the control cases (2 M, 3 F, 20-76 years), of cases showing slight vascular proliferation, dermal fibrosis and inflammation after radiotherapy of breast cancer (12 F, 48-79 years), of cases of atypical vascular lesions after radiotherapy (16 F, 29-81 years), and of cases of angiosarcomas of skin and soft tissues unrelated to radiotherapy (3 M, 5 F, 25-92 years) showed an amplification of MYC by FISH analysis. In striking contrast, in all cases of postradiation cutaneous angiosarcomas (25 F, 46-95 years), MYC amplification was found by FISH analysis in a variable number of counted nuclei. Immunohistochemically, strong positive nuclear staining for MYC and prox-1 was seen in cases of postradiation cutaneous angiosarcoma, whereas control cases and cases of atypical vascular proliferation after radiotherapy were negative for MYC, and stained only focally positive for prox-1 in a number of cases. In conclusion, the presence of MYC amplification represents an important additional diagnostic tool in the distinction of postradiation cutaneous angiosarcomas from atypical vascular lesions after radiotherapy. Immunohistochemical stainings for MYC are useful for mapping of these lesions and for careful tumor margin control.
Modern Pathology 09/2011; 25(1):75-85. · 4.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The incidence of syphilis is increasing in many parts of the world including a re-emergence in Western Europe and North America. Depending on the disease stage, direct detection of Treponema pallidum in mucocutaneous lesions of syphilis may be difficult and histopathological findings are not always straightforward. Thus, the correct histological diagnosis may be challenging.
Comparatively to evaluate the evidence for infection with T. pallidum by immunohistochemistry (IHC), polymerase chain reaction (PCR) and focus-floating microscopy (FFM).
A series of 86 paraffin-embedded skin biopsy samples from patients with primary, secondary or tertiary syphilis was assessed for detection of T. pallidum by IHC and FFM; 45 specimens were also investigated by a T. pallidum-specific PCR analysis. Histopathological reaction patterns and number and distribution of treponemes were studied, and all data were re-evaluated by clinicopathological correlation.
Using a polyclonal antibody directed against T. pallidum, we detected the presence of T. pallidum by IHC in 42/86 (49%) samples [6/9 (67%) primary, 34/62 (55%) secondary and 2/15 (13%) tertiary syphilis]. T. pallidum-specific DNA was detected in 31/45 (69%) specimens [4/4 (100%) primary, 26/34 (76%) secondary and 1/7 (14%) tertiary syphilis]. In comparison, FFM analysis resulted in an overall detection rate of 82/86 (95%) [9/9 (100%) primary, 60/62 (97%) secondary and 13/15 (87%) tertiary syphilis]. Significant differences were observed concerning amount and distribution of organisms (epitheliotropic vs. endotheliotropic) in correlation to the three disease stages and to histopathological reaction patterns.
FFM is a highly sensitive and specific method to detect T. pallidum in tissue from mucocutaneous syphilis lesions. Our results indicate that a combination of PCR and FFM, as the most sensitive approach, could provide an additional benefit for the histopathological diagnosis of (late) secondary and tertiary syphilis and may be helpful in cases where serological testing of T. pallidum antibodies has failed, but the clinical suspicion for syphilis remains.
British Journal of Dermatology 03/2011; 165(1):50-60. · 3.67 Impact Factor
-
K D Mertz,
M Schmid,
B Burger,
P Itin,
G Palmedo,
L Schärer, H Kutzner,
M T Fernández Figueras,
B Cribier,
M Pfaltz,
W Kempf
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUNd: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias.
To examine whether EV is associated with cutaneous MCPyV infection.
We used MCPyV-specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient with acquired EV.
In all congenital EV patients, MCPyV DNA was found in carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In 4 of these patients, the MCPyV-positive skin lesions were from different anatomic locations. In addition, 1 immunosuppressed patient suffering from acquired EV harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of 30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV DNA.
The strong association of EV-associated skin neoplasms with MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV. Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the development of EV-associated skin neoplasms.
Dermatology 01/2011; 222(1):87-92. · 2.05 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A number of hereditary tumor syndromes are associated with characteristic dermal neoplasms and knowledge and early diagnosis of these lesions may facilitate the diagnostic of the underlying syndrome. These syndromes include Muir-Torre syndrome, associated with cystic sebaceomas, Cowden syndrome, associated with multiple tricholemmomas, Carney complex associated with multiple superficial angiomyxomas, Birt-Hogg-Dubé syndrome associated with multiple fibrofolliculomas, tuberous sclerosis associated with multiple facial angiofibromas and so-called Koenen tumors, patients with renal cell cancer associated with pilar leiomyomatosis and uterine leiomyomas, Gardner syndrome associated with Gardner fibromas and nevoid basal cell carcinoma associated with multiple basal cell carcinomas in young patients.
Der Pathologe 10/2010; 31(6):489-96. · 0.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Primary cutaneous CD30+ lymphoproliferative disorders include lymphomatoid papulosis (LyP) and primary cutaneous CD30+ anaplastic large T-cell lymphoma (ALCL). Because of overlapping histological features, it is impossible to distinguish ALCL from LyP on histological grounds. MUM1 (Multiple Myeloma oncogene 1) is expressed in systemic ALCL and classical Hodgkin lymphoma. MUM1 expression has not been studied in detail in CD30+ lymphoproliferative disorders.
To examine the expression of MUM1 in CD30+ lymphoproliferative disorders and to assess its value as a diagnostic marker.
Thirty-one formalin-fixed paraffin-embedded specimens of LyP (n = 15), primary cutaneous ALCL (n = 10), secondary cutaneous infiltrates of systemic ALCL (n = 4) and secondary cutaneous Hodgkin lymphoma (n = 2) were analysed by immunohistochemistry with a monoclonal antibody against MUM1.
Positive staining for MUM1 was observed in 13 cases of LyP (87%), two cases of primary cutaneous ALCL (20%), four cases of secondary cutaneous ALCL (100%) and two cases of secondary cutaneous Hodgkin lymphoma (100%). In 11 of 13 LyP cases (85%), MUM1 was displayed by the majority, i.e. 50-90%, of the tumour cells. In contrast to LyP and secondary cutaneous ALCL, only two cases of primary cutaneous ALCL (20%) harboured MUM1-positive tumour cells. There was a statistically significant difference in the expression of MUM1 between LyP and primary cutaneous ALCL (P = 0.002) and between primary cutaneous ALCL and secondary cutaneous ALCL (P = 0.015).
MUM1 expression is a valuable tool for the distinction of LyP and ALCL and thus represents a novel adjunctive diagnostic marker in CD30+ lymphoproliferative disorders.
British Journal of Dermatology 07/2008; 158(6):1280-7. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Necrobiosis lipoidica (NL) is a chronic inflammatory skin disease with unknown aetiology. The aim was to determine the presence of spirochaetal microorganisms in NL.
Focus-floating microscopy (FFM) is a modified immunohistochemical technique that was developed to detect borrelial spirochaetes within tissue sections. It has proven to be more sensitive for the detection of spirochaetes than polymerase chain reaction (PCR). Fifty-six cases of NL as well as 44 negative and 33 positive controls were investigated for the presence of Borrelia within tissue specimens. Using FFM, Borrelia could be detected in 42 cases (75.0%) and were seen significantly more often in histologically active inflammatory-rich (38/41, 92.7%) than in inflammatory-poor (4/15, 26.7%) cases of NL (P < 0.001). Seven cases investigated with a Borrelia-specific PCR (23s-RNA) remained negative. In contrast, FFM was positive in 30 of 33 (90.9%) positive controls of acrodermatitis chronica atrophicans and 15 of the positive controls (45.5%) were also positive with PCR, whereas no negative controls revealed any microorganisms.
Detection of spirochaetes in NL points to a specific involvement of B. burgdorferi or other similar strains in the development of or trigger for this disease.
Histopathology 06/2008; 52(7):877-84. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Spindle cell and epithelioid cell differentiation occur in both benign and malignant hyperpigmented melanocytic lesions. Reed nevus is characterized by compact, sharply circumscribed junctional cellular nests composed of slender hyperpigmented melanocytes shaped like spindle cells. Deep penetrating nevus is characterized by a diffuse dermal proliferation composed of small nests and fascicles of pale ovoid and epithelioid melanocytes. Cellular blue nevi often have a characteristic hourglass or dumbbell shape, with sharply circumscribed elongated nests and fascicles of pale, densely layered ovoid melanocytes and adjacent melanophages. Epithelioid blue nevus is characterized by large epithelioid melanocytes with abundant cytoplasm and melanin often concentrated to some degree in the cell membrane. Animal-type melanoma is a particularly hyperpigmented variant of melanoma in which large melanophages predominate and there are varying proportions of melamin-rich spindle-shaped and large atypical epithelioid melanocytes. Morphologically, pigmented epithelioid melanocytoma combines characteristics of both animal-type melanoma and pigmented epithelioid nevus. Malignant melanoma may occur in conjunction with a preexistent blue nevus. Malignant blue nevus is now regarded as a malignant melanoma mimicking a blue nevus in structure and pattern. It is therefore of paramount importance to view multiple mitoses within a cellular blue nevus-like proliferation as an alarm signal as they are usually indicators of a malignant melanoma.
Der Pathologe 12/2007; 28(6):411-21. · 0.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Clinicopathologic correlation is the basis of a precise diagnosis. Especially in dermatopathology, the precision of a microscopic diagnosis may significantly be increased by thorough knowledge of the clinical picture. The advent of digital photography, the internet and moderately priced CDs and USB-sticks have made it possible to establish and maintain a time-saving, low-cost picture data transfer between dermatologist and dermatopathologist which is optimally suited for clinicopathologic correlation.
Der Hautarzt 10/2007; 58(9):760-8. · 0.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Die klinisch-pathologische Korrelation ist das Fundament, auf dem jede korrekte Diagnose ruht. Insbesondere in der Dermatopathologie
wird die Präzision der feingeweblichen Beurteilung durch genaue Kenntnis des dermatologischen Status maßgeblich gesteigert.
Digitale Fotografie, Internet und kostengünstige Datenträger machen es möglich, zwischen behandelnden Dermatologen und assoziierten
Dermatopathologen einen kostenneutralen und zeitsparenden Bildtransfer für eine optimale klinisch-pathologische Korrelation
aufrechtzuerhalten.
Clinicopathologic correlation is the basis of a precise diagnosis. Especially in dermatopathology, the precision of a microscopic
diagnosis may significantly be increased by thorough knowledge of the clinical picture. The advent of digital photography,
the internet and moderately priced CDs and USB-sticks have made it possible to establish and maintain a time-saving, low-cost
picture data transfer between dermatologist and dermatopathologist which is optimally suited for clinicopathologic correlation.
Der Hautarzt 01/2007; 58(9):760-768. · 0.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Paraneoplastic dermatoses are non-neoplastic skin disorders which occur in the context of an underlying malignant neoplasm. The classic paraneoplastic dermatoses are mostly associated with solid internal malignancies. They only rarely occur in the context of nodal or primary cutaneous lymphomas. Apart from these classic paraneoplastic dermatoses, there are additional skin disorders reported to occur in close association with haematological and lymphoproliferative disorders which can thus be regarded as paraneoplastic manifestations. We report for the first time two patients with pityriasis lichenoides et varioliformis acuta in association with mycosis fungoides. In addition, we review the literature on paraneoplastic dermatoses of the skin which have been described in patients with leukaemias and primary cutaneous lymphomas.
British Journal of Dermatology 07/2005; 152(6):1327-31. · 3.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To analyse seven cases of cutaneous myomelanocytic tumour histologically and immunohistochemically. Perivascular epithelioid cell tumours (so-called PEComas) are rare and recently delineated neoplasms occurring in the lung, kidney, pancreas, uterus, falciform ligament, vulva, heart, prostate and soft tissues. PEComas are characterized by a perivascular location of neoplastic cells showing a broad spectrum of epithelioid and spindled cells with clear, and granular pale eosinophilic cytoplasm, and a variable expression of melanocytic and muscle markers, whereas S100 protein and cytokeratins are usually absent.
We report seven cases of cutaneous myomelanocytic tumour arising on the lower (six cases) and upper (one case) extremities of female adults (age range 30-66 years). In all cases an ill-defined dermal lesion with extension into subcutaneous tissue was noted. The neoplasms contained numerous blood vessels with a lace-like pattern and slightly thickened vessel walls, and were composed of perivascular epithelioid cells containing clear or focally granular pale eosinophilic cytoplasm and round vesicular nuclei with small, sometimes slightly enlarged nucleoli. Increased proliferative activity and tumour necrosis were not seen. Immunohistochemically, tumour cells stained positively for HMB-45, microphthalmia transcription factor, and NKIC3 in all cases, whereas perivascular expression of alpha-smooth muscle actin and focal positivity for desmin were noted in one case each only. Two out of four cases tested stained focally positive for calponin. No expression of S100 protein and pancytokeratin was present. Despite incomplete/marginal excision in three cases none of the neoplasms has recurred locally so far.
With the presented series of cutaneous myomelanocytic tumours the clinicopathological spectrum of PEComas is expanded.
Histopathology 06/2005; 46(5):498-504. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Circumscribed acral hypokeratosis is a rare chronic disorder of cornification that occurs predominantly in women. Lesions are solitary and do not respond to any local conservative treatment. They have to be differentiated by biopsy from other non-healing lesions and tumors in acral skin. Clinically lesions appear as sharply circumscribed reddish macules. The histologic hallmark is a circumscribed loss of the entire stratum corneum, which can be best demonstrated at the border of the lesion as a contrast to the perilesional broad stratum corneum typical for acral sites.
Der Hautarzt 12/2004; 55(11):1060-3. · 0.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Die zirkumskripte akrale Hypokeratose ist eine seltene, chronische Verhornungsstrung, die bevorzugt bei Frauen beobachtet wird. Die zumeist solitr auftretenden und therapierefraktren Herde mssen klinisch und histologisch von anderen nicht abheilenden Vernderungen und Tumoren in akraler Haut abgegrenzt werden. Klinisch imponieren die Lsionen als scharf begrenzte erythematse Makulae. Histologisch ist die zirkumskripte akrale Hypokeratose durch einen scharf umschriebenen Verlust der Hornschicht charakterisiert, der sich feingeweblich vor allem in Randbiopsien im Vergleich zur perilsional ortstypisch breiten Hornschicht darstellen lsst.Circumscribed acral hypokeratosis is a rare chronic disorder of cornification that occurs predominantly in women. Lesions are solitary and do not respond to any local conservative treatment. They have to be differentiated by biopsy from other non-healing lesions and tumors in acral skin. Clinically lesions appear as sharply circumscribed reddish macules. The histologic hallmark is a circumscribed loss of the entire stratum corneum, which can be best demonstrated at the border of the lesion as a contrast to the perilesional broad stratum corneum typical for acral sites.
Der Hautarzt 01/2004; 55(11):1060-1063. · 0.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Invasion of squamous cell carcinoma of the head and neck into cutaneous nerves is rare and can easily be missed. Perineural outgrowth into cerebral nerves may result in severe pain or neurological disturbances. In addition, these carcinomas more often recur or metastasize and therefore are associated with a poor prognosis.
We report on two patients with squamous cell carcinoma of the dorsum of the nose and lower lip exhibiting neurotropic growth.
Histology showed pleomorphic keratinocytes growing deep into the subcutaneous tissue and bone, respectively. The presence of few pleomorphic keratinocytes could be only confirmed by immunohistochemistry, though indicated by a perineural lymphocytic infiltrate. In both patients, several re-excisions were necessary to achieve cure.
In neurotropic squamous cell carcinoma a consequent radical micrographic surgery as well as neurological and radiological investigations are mandatory. We also review the literature.
Der Hautarzt 12/2003; 54(11):1087-94. · 0.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hintergrund und FragestellungNeurotropes Wachstum von Plattenepithelkarzinomen des Kopf- und Halsbereiches ist selten und kann leicht verkannt werden. Diese Tumoren knnen unbehandelt entlang kutaner Nervenfasern in Hirnnerven vorwachsen und zu Schmerzen oder neurologischen Strungen fhren. Neurotrope Plattenepithelkarzinome haben eine hohe Rezidiv- und/oder Metastasierungsrate und daher eine schlechte Prognose.Patienten/MethodikWir berichten ber 2Patienten mit Plattenepithelkarzinom des Nasenrckens bzw. der Unterlippe mit neurotropem Tumorwachstum.ErgebnisseIn beiden Fllen fanden sich bis in die Subkutis bzw. den Knochen vorwachsende Karzinomanteile. Histologisch waren die wenigen pleomorphen Tumorzellen in den Nerven erst zuverlssig in immunhistochemischen Frbungen zu erkennen; wegweisend waren lymphozytre Infiltrate um die Nerven. Bei beiden Patienten waren mehrere Nachexzisionen notwendig, um den Tumor im Gesunden zu entfernen.SchlussfolgerungenBei neurotropen Plattenepithelkarzinomen des Gesichts- und Halsbereichs sind eine konsequente radikale Exzision mit Schnittrandkontrollen sowie ggf. neurologische und radiologische Untersuchungen notwendig. Die vorliegende Arbeit gibt eine bersicht ber die bislang publizierten Flle.Background and objectiveInvasion of squamous cell carcinoma of the head and neck into cutaneous nerves is rare and can easily be missed. Perineural outgrowth into cerebral nerves may result in severe pain or neurological disturbances. In addition, these carcinomas more often recur or metastasize and therefore are associated with a poor prognosis.Patients/MethodsWe report on two patients with squamous cell carcinoma of the dorsum of the nose and lower lip exhibiting neurotropic growth.ResultsHistology showed pleomorphic keratinocytes growing deep into the subcutaneous tissue and bone, respectively. The presence of few pleomorphic keratinocytes could be only confirmed by immunohistochemistry, though indicated by a perineural lymphocytic infiltrate. In both patients, several re-excisions were necessary to achieve cure.ConclusionsIn neurotropic squamous cell carcinoma a consequent radical micrographic surgery as well as neurological and radiological investigations are mandatory. We also review the literature.
Der Hautarzt 10/2003; 54(11):1087-1094. · 0.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mutational acivation of the RAS/RAF/MAPK pathway has a central role in proliferation of melanocytes. A single point mutation in exon 15 of the BRAF gene has recently been reported in a high percentage in cultured melanoma cells and in 6 of 9 primary melanomas examined. The high frequency of BRAF mutations was considered to be a possible target for therapy of advanced stages of malignant melanoma. To clarify the role of the T1796A BRAF mutation in tumorigenesis of malignant melanoma and to evaluate its presence in benign melanocytic lesions, we screened primary malignant melanomas, malignant melanoma in situ, various types of melanocytic nevi (e.g. congenital, dysplastic, intradermal), Spitz nevi and malignant melanoma with an underlying nevus by single-strand conformational polymorphism (SSCP) and direct DNA sequencing for the presence of mutations of the BRAF gene. The frequency of the specific T1796A mutation in malignant melanoma was with 29% (28/97) considerably low. Melanoma metastases showed a similar rate (21%) as the primary melanomas (3/14) Moreover we could detect the mutation in several non-malignant melanocytic skin lesions (39/187). Spitz nevi (0/63), which histologically can resemble malignant melanoma, and blue nevi (0/19) did not show any mutated cases, while papillomatous nevi (20/27) showed the highest frequency of mutations (74%). In melanomas with an underlying nevus the mutation was either present in both the laser-capture microdissected nevus cells and the microdissected melanoma cells or both lesions were negative for the BRAF mutation except one case, supporting the theory of the nevus progressing into a malignant melanoma. We screened 312 (including 103 microdissected tissue samples) melanocytic skin lesions for the presence of the specific BRAF mutation. As the mutation could be found in similar frequency in both malignant and benign lesions, we conclude that the T1796A mutation of the BRAF gene is non-specific for progression of a nevus to a melanoma. Other so far unknown cofactors seem to be of importance and further studies have to be undertaken to clarify the role of T1796A for the RAS/RAF/MAPK pathway.
Pigment Cell Research 09/2003; 16(5):580-580. · 4.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Dermatomyofibroma (plaque-like dermal fibromatosis) represents a distinct clinicopathological entity in the spectrum of cutaneous mesenchymal neoplasms showing a myofibroblastic line of differentiation. These benign neoplasms occur frequently, but not exclusively, in young women, and the shoulder girdle as well as the upper trunk are common locations. Histologically, dermatomyofibroma is characterized by a plaque-like proliferation of cytologically bland spindle-shaped tumour cells containing an ill-defined, pale eosinophilic cytoplasm and elongated, neuroid nuclei. Neoplastic cells are arranged in bundles and fascicles orientated parallel to the skin surface, adnexal structures are spared and elastic fibres are increased and fragmented. Immunohistochemically, tumour cells express vimentin and variably muscle actin and alpha-smooth muscle actin, but are negative for desmin, CD34, S100, and epithelial markers. The main differential diagnosis includes hypertrophic scar, dermatofibroma (fibrous histiocytoma), pilar leiomyoma, neurofibroma, adult myofibromatosis, extra-abdominal fibromatosis and plaque-stage dermatofibrosarcoma protuberans.
We report three cases of dermatofibroma arising in male patients aged 31, 36, and 47 years on the thigh, chest wall and back, respectively. All lesions were completely excised and no local recurrence has been reported. Histologically, the neoplasms showed classical features of dermatomyofibroma; however, in addition abundant extravasated erythrocytes, scattered inflammatory cells, numerous capillaries, and sieve- and slit-like spaces, features resembling plaque-stage Kaposi's sarcoma, were noted. In none of the cases did spindled tumour cells stain positively for CD34, and HHV8 was not detected by polymerase chain reaction.
The reported cases widen the clinicopathological spectrum of dermatomyofibroma and emphasize plaque-stage Kaposi's sarcoma as an additional differential diagnosis.
Histopathology 07/2003; 42(6):594-8. · 3.08 Impact Factor
