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FIBROEPITELIOMUL. TUMORA PINKUS

FIBROEPHITELIOMA. PINKUS TUMOR.

OLIVER GHENUCHE*, ALICE RUSU*, MARIA GRIGORE*, VASILE BENEA*, SIMONA ROXANA GEORGESCU*

Rezumat

Fibroepiteliomul este o tumorã rarã, descrisã de cãtreHermann Pinkus în 1953, ca fiind o leziune premalignãfibroepitelialã. El a considerat cã fibroepiteliomul este ovariantã de carcinom bazocelular, ce ilustreazãinteracþiunea ºi interdependenþa componentelor stromale ºiepiteliale ale carcinomului bazocelular.

Va prezentãm 3 cazuri de Fibroepiteliom diagnosticatehistopatologic în clinica noastrã în ultimele 12 luni.

Cuvinte cheie: Fibroepiteliomul Pinkus, aspecteclinice, dermatoscopice ºi histopatologice.

Summary

The Fibroephitelioma is a rare tumor, first described byHermann Pinkus in 1953, as a premalignant lezion. Hebelived the Fibroephitelioma to be a variant of BasocellularCarcinoma, one witch illustrates the interaction andinterdependence of the stromal and the ephitelialcomponents of BCC. We present 3 cases of PinkusFibroephitelioma Diagnosed histologically in our clinicover the last 12 months.

Key words: Pinkus Fibroephitelioma; clinical,dermatoscopic and histologic aspects.

* Secþia Clinicã de Dermatovenerologie - Spitalul Clinic de Boli Infecþioase ºi Tropicale “Dr. Victor Babeº” - Bucureºti.Dermatology Department - Infectious and Tropical Disease Clinical Hospital “Dr. Victor Babes“ - Bucharest, Romania

Intrat în redacþie: 10.11.2014

Acceptat: 28.11.2014

Received: 10.11.2014Accepted: 28.11.2014

Cazul 1

D.P. în vârstã de 55 ani, sex masculin, s-aprezentat pentru consult dermatologic datoritãunei plãci eritematoase infiltrate, rotundã, binedelimitatã, cu diametrul de 1cm, localizatã lanivelul fesei drepte, pe care pacientul a observat-ode aproximativ 3 luni.

Diagnosticul clinic: Verucã seboreicã sauBoala Bowen.

Histopatologic: Tegument prezentând lanivelul dermului papilar ºi reticular superiorproliferare de celule bazaloide dispuse în travee anastomozante, paralele cu epidermul,având conexiuni cu acesta. Diagnostic: TumoraPinkus.

Case 1

D.P. 55 years old, male, requested adermatology consult because of an infiltratederythematous plaque, round shaped, welldelimited, 1 cm in diameter, located on the rightbuttocks, witch the pacient noticed in the last 3months.

Clinical Diagnostic: Seborrheic Keratosis orBowen’s Disease.

Histology: Tegument displaying bazaloid cellproliferation arranged in anastomosing strandslocalized in the papillary and reticular dermis,parallel to the epidermis, connected to it.Diagnosis: Pinkus Fibroepithelioma.

CAZURI CLINICECLINICAL CASES

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Cazul 2

E.S. în vârstã de 70 ani, sex masculin,cunoscut cu Epiteliomatozã bazocelularã s-aprezentat pentru reevaluare. S-au excizat 3formaþiuni tumorale de la nivel lombar: oformaþiune eritematoasã, nodularã, ulceratãcentral, cu diametrul de 1 cm ºi douã plãcieritematoase de 0.4 ºi respectiv 0.5 cm. S-aformulat diagnosticul clinic de CarcinoameBazocelulare multiple ºi s-a efectuat biopsia lor.

Examenul histopatologic a relevat cã unadintre leziuni era formatã preponderent din benzide celule bazaloide anastomozante cu localizaresuperficialã. Diagnostic: Tumora Pinkus.Epitelioame bazocelulare multiple.

Case 2

E.S. 70 years old, male, previously diagnosedwith Basal Cell Epitheliomatosis comes in for acheck up. 3 tumoral lesions from the lower backwere surgically excised: One nodular erythe-matous lesion, 1 cm in diameter and twoerythematous plaques 0.4 and 0.5 cm indiameter. The clinical diagnosis proposed wasmultiple Basal Cell Carcinomas. They werebiopsied.

The biopsy revealed that one of the lesionswas mostly formed out of anastomosing basalcell strands with a superficial localisation.Diagnosis: Pinkus Fibroephitelioma. MultipleBasal Cell Carcinomas.

Fig. 1. D.P. 55 ani, aspect clinicFig. 1. D.P. 55 years, clinical aspect

Fig. 3. D.P. 55 ani. Col. H&E. 10x. Travee anastomozanteformate din celule bazaloideFig. 3. D.P. 55 years. Col. H&E. 10x. Anastomosing strands ofbasaloid cell proliferation

Fig. 2. D.P. 55 ani. Col. H&E. 4x. Travee anastomozante

formate din celule bazaloide

Fig. 2. D.P. 55 years Col. H&E. 4x. Anastomosing strands

of basaloid cell proliferation

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Cazul 3

F.M. în vârstã de 64 ani, sex masculin, asolicitat consult dermatologic pentru o leziunetumoralã rotund-ovalarã de 4 cm în diametru,brun-deschis-roºiaticã, depresionarã, bine delimi-tatã, localizatã toracal posterior, interscapular.Pacientul afirmã cã leziunea evolueazã deaproximativ 30-35 ani, aspectul iniþial fiind deleziune proeminentã, hiperkeratozicã, închisã laculoare, aspectul actual fiind observat de aprox. 5ani.

Diagnostic clinic: Carcinom Bazocelular sauKeratozã seboreicã.

Examenul histopatologic descrie aspect defibroepiteliom alcãtuit din proliferãri tumorale

Case 3

F.M. 64 years old, male, was examinedbecause of a tumoral lesion round-ovoloid inshape, 4 cm in diameter, light-brown-redish,lowered, well delimited, located in the

Fig. 4. E.S. 70 ani. Aspect clinicFig. 4. E.S. 70 years. Clinical aspect. Black arrow: excised

nodular lesion; White arrow: melanocytic lesion

Fig. 6. F.M. 64 ani. Aspect clinic. DetaliuFig. 6. F.M. 64 years. Clinical aspect. Detail

Fig. 7. F.M. 64 ani. Aspect dermatoscopic: leziune cuaspect roºiatic, cu arii pigmentare distribuite neregulat,

astructurale, de culoare brun-deschis-gri; prezenþa câtorvaleziuni vasculare punctiforme, ºi a câtorva zone albe

astructuraleFig. 7. F.M. 64 years. Dermatoscopic aspect: lesion with

overall reddish colour, irregular, non-structured pigmentedareas (light-brown to gray); few punctiform vascular

lesions; white structureless areas

Fig. 5. F.M. 64 ani. Aspect clinicFig. 5. F.M. 64 years. Clinical aspect

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dense, formate din celule de tip bazal, sub formade cordoane ce se anastomozeazã între ele.Prezenþa de melanocite aminteºte de aspectulhistopatologic al keratozelor seboreice reticulate.

Discuþii

Fibroepiteliomul este o tumorã rarã, descrisãprima datã în 1953 de cãtre Hermann Pinkus, cafiind o leziune premalignã fibroepitelialã. Pinkusa observat cã leziunile aveau un aspect histo-patologic ciudat, semãnând atât cu keratozeleseboreice reticulate cât ºi cu carcinoamelebazocelulare. El a considerat cã fibroepiteliomuleste o variantã de carcinom bazocelular, ceilustreazã interacþiunea ºi interdependenþacomponentelor stromale ºi epiteliale ale carci-nomului bazocelular. [3, 5]

Ultimele cercetãri din domeniul biologieimoleculare orienteazã asupra mecanismeloretiopatogenice de producere a cancerelor non-melanocitare (inclusiv fibroepiteliomul). Seconsiderã cã deleþia sau mutaþia genei TP53 ducela scãderea controlului proliferãrii celulare. Altãgenã consideratã implicatã în etiopatogenie estegena PATCHED. Mutaþia sa eliminã un semnalinhibitor al cãii Hedgehog ce regleazã proli-ferarea celularã. Pierderea acestei inhibiþii duce laexpresia accentuatã a unor factori transcriptori,ce promoveazã creºterea celularã. [5]

interscapular region. The patient says that thelesion has been evolving for the last 30-35 yearsand that the initial aspect used to be that of araised, dark colored, hiperkeratotic lesion andthat the current aspect is 5 years old.

Clinical diagnosis: Basal Cell Carcinoma orSeborrheic Keratosis.

The histologic examination describes apattern compatible with Pikus Fibroephitelioma:dense tumoral proliferations comprised of basalcells, forming anastomosing strings. Thepresence of melanocytes gives the pattern aReticulated Seborrheic Keratosis resemblance.

Discussions

The Fibroephitelioma is a rare tumor, firstdescribed by Hermann Pinkus in 1953, as apremalignant lezion. Pinkus noticed that thelesions had a weird histologic aspect, resemblingboth Basal Cell Carcinoma and ReticulatedSeborrheic Keratosis. He belived theFibroephitelioma to be a variant of BasocellularCarcinoma, one witch illustrates the interactionand interdependence of the stromal and theephitelial components of BCC. [3, 5]

The latest research in molecular biologyexplains some of the etiopathogenic mechanismsinvolved in non-melanocytic cancer development(including Fibroephitelioma).

Fig. 8. F.M. 64 ani. H&E, 10X, cordoane anastomozante decelule bazaloide, aranjament în palisadã la periferie

Fig. 8. F.M. 64 years H&E col., 10X, basal cellsanastomosing strands, with a palisade arrangement at the

periphery

Fig. 9. F.M. 64 ani. Col. H&E, 40X, cordoane subþiri decelule bazaloide, prezenþa de melanocite oferã aspect

asemãnãtor keratozelor seboreice reticulateFig. 9. F.M. 64 years H&E col., 40X, thin basal cell

strands, the presence of melanocytes gives the pattern aReticulated Seborrheic Keratosis resemblance

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Majoritatea autorilor au acceptat tumoraPinkus ca fiind o variantã de Carcinombazocelular. Unii autori considerã cã leziuneaîncepe prin invazia unui duct ecrin de cãtre uncarcinom bazocelular. Ulterior distrugerealumenului ductal explicã aspectul histopatologicdistinct al fibroepiteliomului. Alþi autoriconsiderã tumora Pinkus înruditã mai mult cutumori benigne ale foliculului pilos precumtricoblastomul sau tricoepiteliomul decât cucarcinomul bazocelular. Existã articole carecomparã carcinomul bazocelular ºi fibro-epiteliomul verificând prezenþa de celule Merkelprin imunohistochimie. Celulele Merkel au fostidentificate în multe tumori benigne foliculare.

Un articol prezintã cazul unei paciente cudouã leziuni tumorale cutanate concomitent: unfibroepiteliom ºi un carcinom bazocelular.Analiza imunohistochimicã a evidenþiat prezenþade celule Merkel doar în tumora Pinkus.[3, 5]

Din punct de vedere epidemiologic,fibroepiteliomul are o incidenþã scãzutã înpopulaþie. Se aproximeazã la 1.2 % din totalulcarcinoamelor bazocelulare primare. Apare maides la persoanele cu fototip deschis ºi distribuþiape sexe este aparent egalã, deºi unii autoriconsiderã o incidenþã mai mare în rândulfemeilor. În majoritatea cazurilor cunoscutetumora era prezentã la persoane între 40 ºi 60 deani, dar au fost descrise ºi câteva cazuri la copii.Durata de timp între apariþia iniþialã a leziunii ºiconfirmarea histopatologicã a diagnosticului estevariabilã. Poate varia de la câteva luni la câþivaani. Însã, în multe dintre cazurile raportate,aceastã duratã este fie necunoscutã, fienemenþionatã. [4, 5]

Aspect clinic

Majoritatea fibroepitelioamelor sunt asimpto-matice. Tumora Pinkus se poate dezvolta solitarãsau asociatã cu alte tumori (cel mai des altecarcinoame bazocelulare sau keratoze seboreice).Clinic fibroepitelioamele au aspect benign, cu ocreºtere lentã, sunt tumori solide elevate,papiloame pedunculate sau fibroame sesile cu obazã largã de implantare, de dimensiunivariabile. Culoarea este de obicei roz-roºiaticã darpot avea nuanþe de brun-deschis. Fibro-epitelioamele se localizeazã de obicei în zonalombo-sacratã, dar se întâlnesc ºi în alte regiuniprecum extremitãþile, toracele posterior,

It is belived that the deletion or mutation ofthe TP53 gene leads to a decrease in cellularproliferation control. Another gene considered tobe involved is the PATCHED gene. It’s mutationeliminates a Hedghog pathway inhibitor signalthat regulates cell proliferation. This inhibitionloss leads to the hiper expresion of transcriptionfactors, that in turn promote cellular growth. [5]

Most authors accept Fibroephitelioma ofPinkus to be a form of BCC. Others believe thatthe lesions begins when an eccrin duct is invadedby a BCC. The ulterior distruction of the eccrinduct lumen explaining the distinct histologicpatterns seen in Pinkus tumor. Some authorsconsider Pinkus Tumor to be more closely relatedto benign pilosebaceous tumors liketricoepithelioma or tricoblastoma that with BCC.There are articles that compare Fibroephiteliomaand BCC, by checking for Merkel cell presenceusing immunohistochemistry. Merkel cells havebeen identifiend in some benign pilosebaceoustumors.

One article describes the case of a patientwith two simultaneous tumor lesions: oneFibroepithelioma and one BCC. Immuno-histochemical analysis descoverd that only thePinkus tumor had Merkel cells. [3, 5]

Epidemiology: Fibroepithelioma of Pinkus hasa low incidence in the population. It isaproximated to be at about 1.2 % of total primaryBasal Cell Carcinoma. It occurs more often inpeople with light skin, and sex distribution seemsto be equal, although some argue a higherincidence in women. The majority of known casesoccured in patients aged 40 to 60, with few casesinvolving children. The time between initial lesiondiscovery and histophatologic confir-mation ofdiagnosis can vary, ranging from a few months toyears. In most reported cases however, thisduration is either unknown or unmentioned. [4, 5]

Clinical aspect

Most Fibroepitheliomas are asimptomatic.The Pinkus Tumor can occur solitarily orassociated with other tumors (most often BCC orSeborrheic Keratosis). Clinically, Fibro-epitheliomas have a benign appearance, they areslow growing, solid elevated tumors,pedunculated papillomas or sesile fibromas witha wide base, of various sizes. The colour is

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abdomenul sau zona genitalã. Au fost descrisefibroepiteliome cu formã chisticã, pleomorfã,erodate sau gigante. [4, 2, 6, 7, 8]

Diagnosticul diferenþial include:

Nev melanocitic intradermic, fibrom pedun-culat, papilom fibroepitelial, granulom,hemangiom, melanom amelanotic, neurofribom,keratozã seboreicã, nev sebaceu. [2, 6, 7, 8]

Existã studii recente ce au încercatsistematizarea elementelor dermatoscopice dinfibroepiteliom. Deºi aceste studii au fost fãcute peun eºantion mic de pacienþi, câteva caracteristicise întâlnesc mai des:

- Leziunile au un aspect roºiatic-brundeschis;

- În majoritatea cazurilor se întâlnesc vasearborescente fine sau elemente vascularepunctiforme;

- Zone pigmentate astructurale brun-gri,distribuite neregulat;

- Linii sau structuri septale albe (cecorespund histologic fibrozei întâlnite înfibroepiteliom);

- Chisturi milia-like;- Ulceraþii.Un studiu din 2006, pe 10 cazuri, a arãtat cã

diagnosticul clinic a fost greºit în toate cele 10cazuri (în 5 cazuri a fost considerat carcinombazocelular), dar corect în 9 din 10 cazuri folosindelementele dermatoscopice descrise anterior. [1]

Diagnosticul de certitudine rãmâne însã celhistopatologic.

Aspectul histopatologic al tumorii Pinkus estedistinct. Cordoane lungi, subþiri, arborizate,anastomozate formate din celule bazaloideînconjurate de o stromã fibrovascularã laxã.Celulele bazaloide sunt de 2 feluri: celuledeschise la culoare, ce reprezintã componentaprincipalã a cordoanelor ºi un numãr mic decelule întunecate, ce mãrginesc porþiuni dincordoane, într-un aranjament în palisadã. Unelecordoane au legãturi cu epidermul. Tumora estesuperficialã ºi bine delimitatã la limita sainferioarã. Hiperkeratoza este rarã.

Diagnosticul diferenþial histopatologic se facecu keratoza seboreicã reticulatã, carcinomul bazo-celular superficial, tricoepiteliomul, tricoblastomulºi siringo-fibro-adenomul ecrin.[5, 6, 7, 8, 9, 10]

Tratamentul recomandat este cel chirurgical.Opþiunile sunt similare celor din alte forme de

usually pink to reddish but can sometimes belight-brown. Pinkus Fibroepithelioma is usuallyreported to be located on the lower back, but canbe found in other regions of the body: limbs,posterior thorax, abdomen, genital area. Cystic,pleomorphic, eroded or giant variants have beendescribed. [2, 4, 6, 7, 8]

Differential diagnosis:

Intradermal melanocytic nevus, peduncu-lated fibroma, fibroepithelial papilloma,granuloma, hemangioma, amelanotic melanoma,neurofibroma, seborrheic keratosis, sebaceousnevus. [2, 6, 7, 8]

Recent studies have tried to systemizedermatoscopic elements found inFibroepithelioma. Although these studiesincluded few patients, some characteristics arefound more often:

- Lesions have a reddish to light-browncolour;

- In most cases thin arborescent vessels andpunctiform vascular elements are found;

- Brown to gray pigmented areas withoutstructure, irregular distribution;

- White lines and septal structures(corresponding histologically with thefibrosis found in Fibroepithelioama);

- Milia-like cysts;- Ulcerations.One study from 2006 that included 10 cases,

showed that the clinical diagnosis was wrong inall cases (5 cases were considered BCC), butcorrect in 9 out of 10 cases when usingdermatoscopic elements previously described. [1]

Certainty Diagnosis is arrived at usinghistopathology.

The histopathologic findings in PinkusTumor is distinct: Long, thin, arborescent,anastomosing strands of basaloid cellssurrounded by a lax fibrovascular stroma. Thereare two types of basaloid cells: light colouredones, witch form most of the strands and a smallnumber of darker cells, found at the periphery ina palisade arrangement. Some strands areconnected to the epidermis. The tumor issuperficial, and well demarcated at its lowerborder. Hyperkeratosis is rare.

Histopathologic differential diagnosis:Reticulated Seborrheic Keratosis, superficialBCC, tricoepithelioma, tricoblastoma or eccrinesyringofibroadenoma. [5, 6, 7, 8, 9, 10]

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carcinom bazocelular. Se recomandã exciziachirurgicalã completã sau electrocauterizareaurmatã de chiuretaj. Se mai pot folosi crioterapia,chirurgia micrograficã Mohs sau radioterapia. [4, 5]

Evoluþie ºi prognostic: Fibroepiteliomul poatefi clasificat în rândul cancerelor maligne de piele,cu potenþial metastatic scãzut. Nu se cunosc pânãîn prezent cazuri de fibroepiteliom care sã ficauzat decesul.

Dezvoltarea unui cancer non-melanoticcutanat predispune pacientul la apariþia unui altcancer cutanat în timp. Aºadar se recomandãmonitorizarea atentã a pacientului pentrueventuala dezvoltare de tumori asemãnãtoare lalocul iniþial sau în alte zone. Se recomandãreexaminare anualã. Pacientul trebuie educat sãevite expunerea solarã ºi bronzatul, sã foloseascãfotoprotecþie adecvatã- SPF 50+. [5]

În concluzie, tumora Pinkus este o afecþiunerarã, cu etiopatogenie incomplet elucidatã, cuaspect clinic foarte variat, dar cu un aspecthistopatologic distinct ce asigurã un diagnosticcorect. Dermatoscopic fibroepiteliomul are câtevaelemente caracteristice ce pot orienta mai binedemersul diagnostic. Tratamentul recomandateste excizia chirurgicalã.

Bibliografie/Bibliography

1. Iris Zalaudek, MD; Gerardo Ferrara, MD; Paolo Broganelli, MD; Elvira Moscarella, MD; Ines Mordente, MD; JasonGiacomel, MD; Giuseppe Argenziano, MD. Dermatoscopy Patterns of Fibroepithelioma of Pinkus. Arch Dermatol.2006; 142(10): 1318-1322. doi:10.1001/archderm.142.10.1318.

2. Martha Viera, MD, Sadegh Amini, MD, Ran Huo, BS, Margaret Oliviero, ARAP, Sara Bassalo, MD, and HaroldRabinovitz, MD; A New Look at Fibroepithelioma of Pinkus. J Clin Aesthet Dermatol. 2008 Jul; 1(2): 42-44.

3. Michael W Su MD PhD, Eric Fromer MD, Maxwell A Fung MD. Fibroepithelioma of Pinkus. Dermatology OnlineJournal 12 (5):2.

4. Philip R. Cohen, MD, Jaime A. Tschen, MD. Fibroepithelioma of Pinkus Presenting as a Sessile Thigh Nodule.Skinmed. 2003;2(6).

5. Darius Mehregan, MD et al; Chief Editor: Dirk M Elston, MD. Premalignant Fibroepithelial Tumor (Pinkus Tumor).Medscape. 2014.

6. Keyvan Nouri MD. Skin Cancer. The McGraw-Hill Companies, Inc. c2008. Chapter 6, Basal Cell Carcinoma; p. 61-85.7. Robert A. Schwartz, MD, MPH, FACP, FAAD. Skin Cancer Recognition and Management. 2nd ed. Blackwell

Publishing; c2008. Chapter 7, Basal Cell Carcinoma; p. 87-104.8. Klaus Wolff, MD, FRCP; Lowell A. Goldsmith, MD; Stephen I. Katz MD, PHD; Barbara A. Gilchrest MD; Amy S.

Paller MD; David J. Leffel MD. Fitzpatrick’s Dermatology in General Medicine. 7th ed. The McGraw-HillCompanies, Inc. c2008. Chapter 115, Basal Cell Carcinoma; p. 1036-42.

9. David E. Elder MB, CHB, FRCPA; Rosalie Elenitsas MD; George F. Murphy MD; Bernett L. Johnson, Jr. MD;Xiaowei Xu MD, PhD. Lever’s Histopathology of the Skin. 10th ed. Philadelphia: Lippincott Williams & Wilkins;c2009. Chapter 29, Tumors and Cysts of the Epidermis; p. 823-35.

10.Phillip H Mckee MD, FRCPath; Eduardo Calonje MD, DipRCPath; Scott R Granter MD et al. Pathology of the skin.3rd ed. Elsevier Mosby.c2005. Chapter 22, Tumors of the surface epithelium - Fibroepithelioma of Pinkus; p. 1186-87.

Conflict de interese Conflict of interestNEDECLARATE NONE DECLARED

Adresa de corespondenþã: Correspondance address:Oliver Ghenuche Oliver Ghenuche

E-mail: oliver.ghenuche@gmail.com E-mail: oliver.ghenuche@gmail.com

Recommended treatment is surgery: Optionsare similar to those in other types of Basal CellCarcinoma: Complete surgical excision orelectrodesiccation followed by curettage.Cryosugery, Mohs micrographic surgery orradiation therapy may also be used. [4, 5]

Evolution and prognosis: Fibroeptheliomacan be classified as a malignant skin cancer, withlow metastatic potential. There are no reportedcases of Piksus tumor related deaths.

History of one skin non-melanocitic cancerpredisposes the patient to the later occurence ofanother skin non-melanocitic cancer. The patientshould be monitored closely, because a similartumor may develop at the initial site or at otherlocations. Annual reexamination is recom-mended. The patient should avoid solar exposureand tanning, while using adequate photopro-tection – SPF 50+. [5]

To conclude, Pinkus Fibroepithelioma is a raredisease, incompletely understood ethiopath-ogenically, with a very diverse clinical aspect, butwith a distinct histopathological pattern. PinkusFibroepithelioma has some dermoscopy featuresthat can better guide the diagnosis. Recommendedtreatment is surgical excision.