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A primary cutaneous adenoid-cystic carcinoma in a youngwoman. Differential diagnosisand clinical implicationsClaudio Cacchi,1 Severino Persechino,2Laura Fidanza,2 Armando Bartolazzi11Pathology Unit, SantAndrea UniversityHospital, Rome, Italy2Dermatology Unit, SantAndreaUniversity Hospital, Rome, ItalyAbstract Primary cutaneous adenoid-cystic carcino-

ma (PCACC) is a rare slow-growing neoplasmof disputed histogenesis characterized by acribriform pattern at histology and localaggressive behaviour. Up to date about 60cases of PCACC have been reported in the lit-erature. This tumour is most common in thescalp, affects middle-aged and older individu-als (mean age 59) and has predilection forwomen. We describe an unexpected case ofPCACC in a 32-years-old woman referred to ourclinic for a subcutaneous nodule in the scalpshowing a slow growth and indolent course.The differential diagnosis and the clinicalmanagement of this PCACC patient, success-fully treated with a wide local excision, are pre-sented and discussed.

IntroductionPrimary cutaneous adenoid cystic carcino-

ma (PCACC) is a rare tumour that affects mid-dle aged and older individuals. It can occur inthe scalp (32-41%), chest and abdomen and ischaracterized by indolent course and localaggressive behaviour.1-7 The average durationof the tumour prior to diagnosis is about 10years. Patients typically present with slowlyexpanding skin coloured nodules from 0.5 to 9cm in size.1-7 If the scalp is involved, alopecia isgenerally an associated finding.3 In the pastPCACC has been regarded as an eccrine lesion,but the possible origin from apocrine glandshas been also proposed.2

Case ReportA 32 years old woman presented with a sub-

cutaneous nodule of the scalp with associatedalopecia (Figure 1). Three years prior to thepresentation she noted an indolent, slowly

expanding firm nodular lesion clinicallyresembling a cutaneous cylindroma or tri-choblastoma. In her medical history there wasno evidence of previous skin lesions or sys-temic tumour diseases. At physical examina-tion no signs of systemic disease were foundand superficial lymph nodes were not palpa-ble. Haematological tests were also in thenormal range. The lesion was surgicallyexcised and submitted for histological exami-nation. Macroscopically the lesion was a

1.91.72.3 cm grey-tan, flesh tumour, withpoorly circumscribed borders. Microscopicallyit showed a characteristic basophilic appear-ance on low power magnification due to thenuclear hyperchromatism. The tumour waspoorly circumscribed and consisted of medi-um-small basaloid cells, with scanty cyto-plasm and small and inconspicuous nucleoli,arranged in islands, cords and strands withglandular, cystic, cribriform architecture,embedded in a fibrous stroma (Figure 2 A andB). The lesion invaded the mid and deep der-mis but not the subcutaneous fat. The basa-loid cells were never displaced in a palisadesfashion and no connection to the overlyingepidermis was observed. Mitotic activity wasvery low (1 mitosis 10 high power field),whereas necrosis, perineural invasion, lym-phatic and/or blood vessels infiltration werenot present. At immunohistochemistry, as expected, the

tumour expressed low and high molecularweight keratins. A variably expression of S-100 protein and carcino-embryonic antigen(CEA) was also observed. The latter wasrestricted to the luminal spaces (data notshown). To better analyze the tumour at phe-notypic level, selected monoclonal antibodiesto type IV collagen and epithelial membraneantigen (EMA) were also considered. The for-mer highlighted the hyaline deposits amongthe basaloid cells and the latter the apicalaspects of pseudoglandular areas (Figure 2).The basophilic intraglandular material, vari-ably detected in the tumour, was also high-lighted with alcian blue staining at pH 2.5 andshowed immunoreactivity for laminin (datanot shown). Both histological and immuno-phenotypical

evaluation suggested the diagnosis of adenoidcystic carcinoma (ACC), but considering therarity of this entity as a primary skin tumour itwas necessary to rule out the possibility of askin metastasis arising from other malignan-cies with histological features of ACC. Adenoid cystic carcinoma, in fact, is most

commonly seen as a neoplasm of the salivaryglands and seromucinous glands of the upperrespiratory tract. It has also been reported tooccur in the breast, lung, uterine cervix,prostate, and lacrimal gland.1,8 As a conse-quence a careful breast and an otolaryngology

examination was performed at specialist level,followed by head and neck ultrasonographicscan. A PET-CT scan was also considered tocomplete the oncological screening.Fortunately, the clinical examination was neg-ative and all the radiological exams resulted inthe normal range. All together, the clinical,morphological and immuno-phenotypical fea-tures described above, supported the finaldiagnosis of a primary cutaneous adenoid cys-tic carcinoma (PCACC). To avoid local recur-rences a wide surgical excision with 2 cm dis-ease-free margins was finally performed. After12 months of follow up the patient is fullyrecovered without any evidence of disease.

Rare Tumors 2011; volume 3:e3Correspondence: Armando Bartolazzi, Dept. ofPathology St. Andrea Hospital,Via di Grottarossa1035, 00189, Rome, Italy. E-mail: armando.bartolazzi@ki.se

Key words: rare skin tumours, primary cutaneousadenoid-cystic carcinoma, differential diagnosis.

Contributions: CC contributed to the histologicaldiagnosis and manuscript writing. Artwork prepa-ration and immunohistochemical procedures; SPclinical management of the patient, surgical pro-cedures; LF clinical management of the patient;collaboration in the manuscript preparation andrevision of the literature; AB histological diagno-sis and paper revision.

Conflict of interest: the authors report no con-flicts of interest.

Received for publication: 5 April 2010.Revision received: 6 December 2010.Accepted for publication: 16 December 2010.

This work is licensed under a Creative CommonsAttribution 3.0 License (by-nc 3.0).

Copyright C. Cacchi et al., 2011Licensee PAGEPress, ItalyRare Tumors 2011; 3:e3doi:10.4081/rt.2011.e3

Figure 1. The clinical picture of the scalplesion with associated alopecia.

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DiscussionPrimary cutaneous adenoid cystic carcinoma

is a rare skin tumour. It was first described byBoggio in the 19753 and, at the best of our knowl-edge, only 61 cases of PCACC have been report-ed in the literature.1-7 This lesion frequently aris-es in the scalp of middle-aged or elderly patient,with a slight predilection for women with anaverage age of 59 years.1 In about 76% of thecases perineural invasion may be observed andthis feature seems to have a prognostic value,with a double increase of relative-risk of localrecurrences when it is detected (46% vs. 22%).1

In the case reported herein the patient is sur-prisingly young (32 years), with only twoyoungest patients (14 years) registered in theliterature.1 The lesion didnt show images of per-ineural invasion nor lymphatic or blood vesselsinfiltration (several histological preparationswere examined). As aforementioned adenoidcystic carcinoma is relatively frequent in thesalivary glands and in this contest it can be anaggressive tumour. ACC has been reported tooccur also in the breast, lung, vulva, cervix andprostate.1,8 Considering the age of the patientand the rarity of this tumour in the skin it wasimperative to rule out a skin metastasis from anACC arising in other organs. This fact has

important clinical implications because theoccurrence of a skin metastasis from a clinical-ly occult ACC requires a more complex oncolog-ical approach for advanced tumour disease. Inour case the negative PET-CT scan and the care-ful clinical evaluation (in particular breast andsalivary glands) allowed the diagnosis of PCACC.As aforementioned PCACC is characterized by aless aggressive behaviour compared to the anal-ogous tumour arising in the salivary gland. Theoccurrence of lung and lymph nodes metastasis,in fact, is exceptionally rare in PCACC,7-10 but,although infrequently, they can be found inACCs arising from salivary gland and breast.Moreover perineural invasion, a hallmark fea-ture of the salivary gland ACCs, may be absent inPCACC, as in the case described here.8 An indo-lent course is the major feature of PCACC with ahigh tendency of local recurrence.1,8 For this rea-son the recommended treatment for PCACC is awide surgical excision with at least 2 cm tumourfree margins.6-11

Differential diagnosisWhen a skin metastasis from an ACC aris-

ing in other organs is definitively ruled out,the differential diagnosis should include sev-

eral primary skin tumours: the adenoid-cysticvariant of basal cell carcinoma (BCC), muci-nous carcinoma (MC) dermal cylindroma (DC)and the primary cutaneous cribriform apocrinecarcinoma (PCCAC). All the mentioned lesionsclosely mimic the PCACC at histology.8,12-13 Thelack of basalioid cells disposed in peripheralpalisades in an adenoid-cystic lesion withoutconnection to the overlying epidermis help thedistinction between a PCACC and the morecommon BCC adenoid-cystic type.8 An otherhelpful histological feature for this differentialdiagnosis is the presence of artefactual cleftsbetween tumour cells and stroma in BCC.8 MCcan be distinguished from a PCACC by histo-chemistry; in fact the former differs fromPCACC in the produced sialomucins.8 In theDC the tumour lobules contain nodulardeposits of hyaline-pink material. Furthermorethe lobules of cylindroma show a mosaic or jig-saw pattern, are surrounded by hyaline materi-al and present peripheral small cells withscanty cytoplasm and dark nuclei.8 Spir -adenoma and spiroadenocylindroma can alsohave an adenoid cystic like pattern, as report-ed by Petersson and colleagues.8,13 However, inthese tumours this feature is always focal(maximum of 2.5 mm). For this reason a sin-gle punch biopsy of such lesions may be notrepresentative for a definitive histologicaldiagnosis. Another findings that lacks inPCACC is the lobular architecture of spirade-noma.8 Primary cutaneous cribriform apocrinecarcinoma (PCCAC) shows a diffuse cribri-form pattern in the entire neoplasia, intercon-nections of the tumour cell aggregates, nuclearpolymorphism and authentic elongated nuclei,features that are absent in the PCACC.12

Opposite to PCCAC, PCACC presents uniformsize and shape spaces between tumour cellaggregates and deposits of basement mem-brane material.8 Finally, the neurotropism,which may be found in PCACC, has been neverobserved in PCCAC.1,8

The histogenesis of PCACC is still uncertainand its apocrine or an eccrine derivation isdebated.14 Concluding, the prompt recognitionof a PCACC is important. Integration of theclinical and histopathological data is essentialfor a correct diagnosis. This will avoid bothpatients distress and unnecessary over treat-ment.

References1. Naylor BA, Sarkar P, Perlis CS, et al.Pimary cutaneous adenoid cystic carcino-ma. J Am Acad Dermatol 2008;58:636-41.

2. Van der Kwast TH, Vuzevski VD,Ramaekers F, et al. Primary cutaneousadenoid cystic carcinoma: case report,immunohistochemistry and review of the

Case Report

Figure 2. Histological and immunohistochemical features of a primary cutaneous ade-noid cystic carcinoma A) Low power view of the tumour demonstrating a poorly circum-scribed neoplasm, which is composed of collection of basophilic cells with cribriformpattern. B) Higher magnification of the lesion showing tumour nests surrounded by aneosinophilic stroma. Nuclear palisading and epidermal contact are absent. C)Immunostaining with mAb to EMA depicts the apical aspect of pseudoglandular spaces.D) The hyaline deposits in small luminal areas among the basophilic cells are immunore-active with mAb to collagen IV.

[Rare Tumors 2011; 3:e3] [page 9]

literature. Br J Dermatol 1988;118:567-7.3. Boggio R. Adenoid cystic carcinoma of thescalp. Arch Dermatol 1975;111:793-4.

4. Barnes J, Garcia C. Primary cutaneousadenoid cystic carcinoma: a case reportand review of the literature. Cutis2008;81:243-6.

5. Seab JA, Graham JH. Primary cutaneousadenoid cystic carcinoma. J Am AcadDermatolol 1987;17:113-18.

6. Irvine AD, Kenny B, Walsh MY, Burrows D.Primary Cutaneous Adenoid CysticCarcinoma. Clin Exp Dermatol 1996;21:249-50.

7. Kato N, Yasukawa K, Onozuka T. Primarycutaneous adenoid cystic carcinoma withlymph node metastasis. Am J Derma -topathol 1998;20:571-7.

8. McKee PH, Calonje E, Granter SR.Pathology of the skin 3rd ed. Philadelphia.Elsevier-Mosby 2005:1653-55.

9. Weekly M, Lydiatt DD, Lydiatt WM, et al.Primary cutaneous adenoid cystic carcino-ma metastatic to cervical lymph nodes.Head Neck 2000;22:84-6.

10. Doganay L, Bilgi S, Aygit C, Altaner S.Primary Cutaneous adenoid cystic carci-noma with lung and lymph node metasta-sis. J Eur Acad Dermatol Venereol 2004;18:383-85.

11. Chesser RS, Bertler DE, Fitzpatrick JE,Mellette JR. Primary cutaneous adenoidcystic carcinoma treated with Mohs micro-graphic surgery toluidine blue technique.J Dermatol Surg Oncol 1992;18:175-76.

12. Rtten A, Kutzner H, Mentzel T, et al.

Primary cutaneous cribriform apocrinecarcinoma: a clinicopathologic and immu -nohistochemical study of 26 cases of anunder recognized cutaneous adnexal neo-plasm. J Am Acad Dermatol 2009;61: 644-51.

13. Petersson F, Kutzner H, Spagnolo DV, et al.Adenoid cystic carcinoma-like pattern inspiradenoma and spiroadenocylindroma: ARare feature in sporadic neoplasms andthose associated with Brooke-SpieglerSyndrome. Am J Dermatopathol 2009;31:642-48.

14. Chu SS, Chang YI, Lou PJ. Primary cuta-neous adenoid cystic carcinoma withregional lymp node metastasis. J LaringolOtol 2001;115:673-75.

Case Report