Michael Wilk

Cutaneous focal mucinosis-A histopathological and immunohistochemical analysis of 11 cases

The histogenesis of cutaneous local mucinosis (CFM) is controversial. Eleven cases of CFM (5F, 6M; mean age 51 years) from our routine files between 1986 and the present time have, therefore, been examined histopathologically and immunohistochemically. Histology revealed an increased number of fibroblast‐like cells in early lesions, whereas they were diminished or predominantly at the margin in advanced ones. The myxomatous areas showed slight to absent reticulum formation. Similarly, elastic fibers were almost absent, and collagen fibers were fragmented and replaced by variable amounts of mucin. One specimen revealed an epithelial component within the lesion reminiscent of a poorly induced trichofolliculoma. Immunohistochemically, vimentin was consistently present and correlated with the number of fibroblast‐like cells. A few (<5%) CD34+ dermal dendritic cells (DDs) were locally seen within CFM. In contrast, FXIIIa+ DDs accounted for up to 30%. Fibroblasl‐like cells were negative for S‐100 protein, Leu7, desmin and α‐SMA. The epithelial component within one of our specimens seems to have been induced by CFM and is a feature also seen in (angio)‐myxomas. CFM appears to be a mesenchymally derived lesion composed predominantly of fibroblasts. DDs do not form the major cell component but rather seem passively incorporated.

Cutaneous angiomyxoma: a benign neoplasm distinct from cutaneous focal mucinosis.

We describe a cutaneous angiomyxoma on the head of a 38-year-old man without evidence of Carneys complex. Complete excision of the tumor appeared to be curative. Histologic examination revealed fibroblast-like cells embedded in a well-demarcated, lobulate, mucinous, and vascularized stroma with a delicate reticulin network. Immunohistologically, the stromal cells were consistently positive for vimentin and focally positive for smooth muscle A-actin but were negative for desmin, KP1, MAC387, factor XIIIa, CD34, Leu-7, and S-100. Cutaneous angiomyxoma appears to represent a myofibroblastic neoplasm that should be distinguished from cutaneous focal mucinosis.

Hailey-Hailey disease and bipolar affective disorder in three members of the same family

Zusammenfassung. Wir berichten über eine Kosegregation von Morbus Hailey-Hailey (MHH) und bipolarer affektiver Erkrankung bei drei Mitgliedern einer Familie. Mit dem Fortschritt molekularbiologischer Techniken ist die Genlokalisation bei Erkrankungen mit einfachem Vererbungsmuster, wie dem autosomal-dominant vererbten MHH, eine Frage der Zeit. Die chromosomale Region des MHH-Gens wird dann auch Kandidatenregion für Kopplungsanalysen bei affektiven Erkrankungen sein.Summary. We report on three family members suffering from both autosomal dominant Hailey-Hailey disease and bipolar affective disorder. As molecular biology techniques have made the localization of genes causing simple Mendelian traits possible as a routine task, the gene for Hailey-Hailey disease will presumably be localized in the foreseeable future. The Hailey-Hailey gene and its chromosomal surrounding will then be a region of interest for linkage studies in bipolar affective disorder.

Chondroid syringoma. Immunohistological evidence for myoepithelial differentiation

Zusammenfassung. Das chrondroide Syringom der Haut gehört wie das pleomorphe Adenom der Tränen- und Speicheldrüse zu den sogenannten Mischtumoren. Die Histogenese dieses seltenen Tumors wird kontrovers diskutiert, insbesondere hinsichtlich seiner stromalen Anteile. Die Verteilung von Zytokeratinen (CK), CEA, EMA, Vimentin, S-100 Protein, Desmin und Aktin (α-smooth muscle actin (α-SMA)) wurde immunhistologisch an Paraffinschnitten eines in toto exzidierten chondroiden Syringoms (Apokriner Typ) untersucht. Die neoplastischen Strukturen wurden hierzu in tubuloalveoläre Areale, solide Nester/Aggregationen sowie stromale Zellen unterschiedlicher Morphologie unterteilt. Die inneren Zellagen tubuloalveolärer Strukturen exprimierten ausgeprägt CK (KL1 und MNF116), CEA und EMA, die äußeren mäßig Vimentin, in geringerem Ausmaß S-100 Protein und schwach KL1, jedoch deutlich und regelmäßig MNF116. Während die soliden Nester deutlich positive Reaktionen für Vimentin, S-100 Protein, MNF116 und schwach für KL1 zeigten, exprimierten die stromalen Zellen intensiv und konstant Vimentin, S-100 Protein sowie fokal CK und α-SMA. Anti-α-SMA weist Myoepithelzellen spezifisch nach. Ferner könnte die teilweise überlappende Expression dieser Intermediärfilamente, Membranantigene und Proteine in den genannten Strukturen darauf hinweisen, daß alle neoplastischen Zellen chondroider Syringome einen gemeinsamen klonalen Ursprung haben.Summary. Chondroid syringoma belongs to the group of so-called mixed tumors, like pleomorphic adenomas of the lacrimal and salivary glands. The histogenesis of this tumour is still disputed, in particular with respect to its stromal component. The distribution of cytokeratins (CKs), CEA, EMA, vimentin, S-100 protein, desmin and actin [α-smooth muscle actin (α-SMA)] was investigated by immunohistological examination of paraffin sections from a chondroid syringoma of the apocrine type. The neoplastic formations have been classified into tubuloalveolar structures, solid nests/aggregations and stromal cells of varying morphology. The innermost cells of tubuloalveolar structures were characterized by marked expression of CKs (KL1 and MNF116), CEA and EMA, while in the outer ones there was moderate expression of vimentin, S-100 was expressed to a lesser extent and KL1, weakly but there was marked and consistent expression of MNF116. Whereas the solid nests expressed vimentin, S-100 protein, MNF116 markedly and KL1 weakly, the stromal cells were consistently positive for vimentin, S-100 protein and, focally, CKs and α-SMA. Anti-α-SMA specifically detects myoepithelial cells. In addition, the partly overlapping immunoreactivity of the intermediate filaments, membrane proteins and proteins in the different structures may indicate a common clonal origin of all neoplastic cells in chondroid syringoma.

Angiomatoid fibrous histiocytoma - case series with emphasis on a late fibrotic variant.

Angiomatoid fibrous histiocytoma (AFH) is a rare, low‐grade malignant, subcutaneous neoplasm in children or young adults.

Circumscribed palmar hypokeratosis: Successful treatment with fluorouracil cream.

IntroductionThe pathogenesis of circumscribed palmar hypokeratosis (CPH) is still controversial, and to date there is no treatment of choice.MethodsWe report on a patient with CPH responding to treatment with fluorouracil cream.ResultsThe clinical course and histopathological features in our observation point towards the possibility of an underlying squamous cell carcinoma in situ presenting as CPH.ConclusionWe suggest that fluorouracil cream treatment should be considered as a therapeutic option in cases of CPH.

Adenolipoma-eccrine and apocrine variants with evidence for a hamartomatous process.

REFERENCES 1. Torres-Álvarez B, Mesa-Garza IG, CastanedoCázares JP, et al. Histochemical and immunohistochemical study in melasma: evidence of damage in the basal membrane. Am J Dermatopathol. 2011;33:291–295. 2. Katz TM, Glaich AS, Goldberg LH, et al. Treatment of melasma using fractional photothermolysis: a report of eight cases with long-term follow-up. Dermatol Surg. 2010;36: 1273–1280. 3. Rokhsar CK, Fitzpatrick RE. The treatment of melasma with fractional photothermolysis: a pilot study. Dermatol Surg. 2005;31:1645–1650. 4. Lee HS, Won CH, Lee DH, et al. Treatment of melasma in Asian skin using a fractional 1,550nm laser: an open clinical study. Dermatol Surg. 2009;35:1499–1504. 5. Choi Y, Chung H, Jung H, et al. Syndecans as cell surface receptors: unique structure equates with functional diversity. Matrix Biol. 2011;30: 93–99.

Atypical fibroxanthoma – what is it, what it is not

To the Editor, We read with interest the article of Pouryazdanparast et al.1 regarding the value of CD163 immunostaining in atypical fibroxanthoma (AFX). In light of the ongoing controversy whether AFX has a mesenchymal or monocytic/macrophage line of differentiation, we offer the following comments based on our data published previously.2– 4 Immunohistochemistry is important in the evaluation of AFX, but its diagnosis is still one of exclusion.5 With the advent of immunoperoxidase markers, it is now generally possible to exclude the main differential diagnoses, namely atypical cutaneous fibrous histiocytoma, leiomyosarcoma, squamous cell carcinoma and melanoma.4,6 Individual cases, however, may have a reduced or only focal immunohistochemical reactivity and must therefore be interpreted with caution. In addition, some tumors have conflicting immunohistochemical results and remain difficult to classify. For tumors that express keratin jointly with mesenchymal determinants, it remains controversial as to whether these lesions should be classified as dedifferentiated examples of spindled squamous cell carcinoma or as examples of AFX with keratin positivity. For those lesions showing dyskeratosis, hints of intercellular bridges, parakeratotic horn pearls and/or coincidence with conventional squamous cell carcinoma (e.g. keratoacanthoma), the former interpretation, in our opinion, is more likely.2 Amongst other immunohistological markers, CD68, CD99, CD10, procollagen-1, p63 and most recently CD163 have been applied to investigate AFX.1 None was sufficient sensitive and specific, and therefore a panel of markers continues to be recommended to investigate cases suspicious for AFX. With respect to CD163, its cytoplasmic/membranous expression has been interpreted as a suggestion that AFX ‘may, in part, be related to histiocytic/dendritic lineage. Alternatively, AFX lesions may have acquired an antigenic determinant of histiocyte/dendrocyte through partial differentiation.’1 We have previously investigated nine cases of AFX with another macrophage marker (Ki-M1p) using double immunostaining with the proliferation marker MIB1 (Ki-67). In this study, we found AFX to be a highly proliferative lesion, up to 40% of tumor cells being positive for MIB1. On the other hand, Ki-M1p positivity was variable with an average of 10–20% of the total cell population and limited to rather bland-appearing cells. Atypical neoplastic cells, especially those positive for MIB1, were negative. While a variable antigenic differentiation within subpopulations of tumor cells in AFX has to be considered, our data suggest that Ki-M1p-positive macrophages represent a reactive rather than neoplastic component in AFX.3,4 For this reason we also regard the presence of KP1 and Ki-M1p-positive osteoclast-like multinucleate giant cells, which have been considered to represent the most extraordinary step of differentiation of neoplastic cells in AFX,7 to be reactive in nature, a phenomenon which can occur in particular when lesions are located close to bone (e.g. temple, acral). We therefore encourage investigation using CD163/MIB1 double immunostaining to further clarify the meaning of CD163 positivity in AFX.

Das epitheloidzellige Histiozytom

ZusammenfassungWir berichten über sieben Beobachtungen dieses seltenen, erst kürzlich beschriebenen, gutartigen Tumors, der klinisch in allen Fällen als solitärer leicht erhabener Knoten von 0,6 bis 1,1 cm Durchmesser an der unteren (n=5) und oberen (n=2) Extremität imponierte. Histologisch zeigte sich in allen Fällen eine gut umschriebene Läsion mit charakteristischer epidermaler Manschette. Überwiegend (60–80%) epitheloide Zellen mit reichlich Zytoplasma, vesikulärem Kern und kleinem Nukleolus sowie zahlreiche erweiterte Blutgefäße kamen zur Darstellung. Diese Zellen reagierten nicht mit Monozyten/Makrophagen Antikörpern (KP1, MAC387). Auch fanden sich keine Hinweise für eine myofibroblastische Differenzierung (Alpha-smooth muscle actin und Desmin negativ). Mit Hilfe immunhistologischer Marker können daher andere Tumoren differentialdiagnostisch abgegrenzt werden, jedoch geben sie keine Information über die Differenzierung epitheloidzelliger Histiozytome. – Unsere hier präsentierten Fälle entsprechen der primär beschriebenen Variante. Kürzlich wurde auch über ähnliche Läsionen im tieferen Korium sowie zellreichere Formen berichtet. So stellt das epitheloidzellige Histiozytom eine charakteristische, bisher wenig bekannte Variante im Spektrum gutartiger fibröser Histiozytome dar, die klinisch und histopathologisch insbesondere vom Nävus Spitz abzugrenzen ist.SummaryWe report on seven examples of this rare, only recently described benign tumor, which presented clinically as solitary elevated nodules on the lower (n=5) and upper (n=2) extremity, measuring between 0.6 and 1.1 cm in diameter. Histologically, all tumors were well-defined with a characteristic epidermal collarette. There were abundant (60–80%) epithelioid cells with prominent cytoplasm, a vesicular nucleus and inconspicuous nucleolus, as well as a number of dilated blood vessels. Immunohistologically, tumor cells did not react with monocyte/macrophage antibodies (KP1, MAC387). In addition, there was no evidence of myofibroblastic differentiation (alpha-smooth muscle actin and desmin negative). Thus, while immunohistological markers are helpful to exclude the diagnosis of other tumors, they do not shed light on the differentiation of epithelioid cell histiocytomas. The present cases are identical to those described originally. Recently similar lesions have been described in deeper parts of the corium as well as more cellular forms. Epithelioid cell histiocytoma represents a characteristic, poorly known variant within the spectrum of benign fibrous histiocytomas; it needs to be distinguished clinically and histopathologically especially from Spitz nevus.

Das sklerotische Fibrom

ZusammenfassungDie klinische und histologische Diagnose sklerotischer Fibrome ist wegen ihrer potentiellen Assoziation mit der Cowdenschen Erkrankung von Bedeutung. Trotz ihrer distinkten histologischen Struktur bleibt die Läsion häufig fehlinterpretiert. Daher berichten wir über 5 eigene Patienten (2W, 3M), bei denen am Kopf (n=2), Arm (n=2) und Bein (n=1) entsprechende Tumoren beobachtet wurden. Die Läsionen imponierten klinisch als weiße bis fleischfarbene harte Knoten, die zwischen 0,5 und 1,2 cm maßen. Klinische Hinweise für das Vorliegen der Cowdenschen Erkrankung fanden sich bei keinem unserer Patienten. Die einfache chirurgische Exzision scheint kurativ zu sein. Histologisch waren die dermalen Tumoren gut umschrieben aber nicht abgekapselt und aus ineinander verflochtenen Kollagenfaserbündeln sowie fibroblastenähnlichen Zellen zusammengesetzt, bei 3 Patienten mit einigen Myofibroblasten. Ca. 50% der Zellen (dermale Dendrozyten (DD)) exprimierten zusätzlich Faktor XIIIa und waren gleichmäßig innerhalb der Tumoren verteilt, im Gegensatz zu den sehr wenigen (<5%) CD34+ DD, die vor allem in den unteren Tumoranteilen beobachtet wurden. Diese Befunde mögen die Verteilung der DD in normaler Haut widerspiegeln. Das sklerotische Fibrom erweitert das Spektrum von Bindegewebstumoren mit potentiell myo-fibroblastischer Differenzierung.SummaryThe clinical and histological diagnosis of sclerotic fibroma is important because of its potential association with Cowdens syndrome. Despite its distinctive histological appearance the lesion is often misdiagnosed. We therefore present five of our own cases (2F, 3M) in which the tumor was located on the head (n=2), arm (n=2) and leg (n=1), respectively. Clinically, the lesions were white to flesh-colored firm nodules ranging in size from 0.5 to 1.2 cm. None of our patients revealed any clinical evidence of Cowdens disease. Simple surgical excision seems to be curative. Histologically, they were well-circumscribed but not encapsulated dermal nodules composed of storiform-arranged sclerosing collagen bundles and vimentin-positive fibroblastlike cells interspersed in three cases by a number of α-smooth-muscle actin-positive myofibroblasts. Approximately 50% of cells (dermal dendritic cells (DD)) also reacted for factor XIIIa evenly scattered throughout the lesion in contrast to the very few (<5%) CD34+ DD found predominantly at the lower border, thus possibly reflecting the distribution of these cells in normal skin. Sclerotic fibroma expands the spectrum of fibrous lesions that may express α-smooth-muscle actin.