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Human Pathology (2013) 44, 1937–1940

Case study

A unique case of sclerosing polycystic adenosis of thesinonasal tract☆

Albert Su MDa, Sunita M. Bhuta MDa, Gerald S. Berke MDb, Chi K. Lai MD, FRCPC c,⁎

aDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USAbDepartment of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USAcDepartment of Pathology and LaboratoryMedicine, The Ottawa Hospital—General Campus, Ottawa, Ontario, Canada K1H 8L6

Received 2 December 2012; revised 20 December 2012; accepted 7 January 2013

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Keywords:Sclerosing polycysticadenosis;

Sinonasal tract;Salivary gland

Summary Sclerosing polycystic adenosis is an extremely uncommon, recently described, sclerosinglesion of the salivary glands that appears histologically similar to fibrocystic changes of the breast. Thekey histopathologic features of sclerosing polycystic adenosis include lobular proliferation of ductal andacinar elements, cystically dilated ducts exhibiting frequent apocrine and sebaceous metaplasia,eosinophilic intracytoplasmic granules within some acinar-type cells, intraductal epithelial hyperplasia,and dense fibrosis. Most described cases have occurred in the major salivary glands, particularly theparotid gland. Although most authorities consider sclerosing polycystic adenosis to be apseudoneoplastic process, the occurrence of dysplasia and carcinoma in situ of ductal epitheliumreported recurrence rates of up to 30%, and recent evidence of clonality suggests a possible neoplasticetiology. However, there have been no cases of metastasis. Herein, we report the first case of sclerosingpolycystic adenosis of the sinonasal tract in a 79-year-old woman presenting with a sinonasal mass.© 2013 Elsevier Inc. All rights reserved.

in the major salivary glands, most commonly the parotid gland

1. Introduction

Sclerosing polycystic adenosis (SPCA) is a rare, sclerosingprocess of themajor andminor salivary glands that was initiallydescribed bySmith et al [1] in 1996. The key histologic featuresof SPCAare lobular proliferation of ductal and acinar elements;cystic ducts with frequent apocrine-like and sebaceous-likecells; eosinophilic cytoplasmic granules within some acinar-type cells; intraductal epithelial hyperplasia with occasionalcollagenous spherulosis; and dense, frequently nodular fibrosis[1]. These histologic features are reminiscent of fibrocysticchanges of the breast. Most of the reported cases have occurred

☆ Conflicts of interest and disclosures: None.⁎ Corresponding author.E-mail address: chilai@toh.on.ca (C. K. Lai).

046-8177/$ – see front matter © 2013 Elsevier Inc. All rights reserved.ttp://dx.doi.org/10.1016/j.humpath.2013.01.017

[1–11]. Only rare cases have been reported in the minorsalivary glands of the oral cavity [12–14]. Herein, we report acase of SPCA involving the sinonasal tract, a novel location forthis entity.

2. Case report

A 79-year-old, otherwise healthy woman presented with aseveral-month history of an enlarging and palpable leftsinonasal mass. Besides a complaint of left-sided epiphora,the patient denied the presence of nasal airway obstruction,epistaxis, drainage, or decreased sensation along thedistribution of the left intraorbital nerve. A preoperativecomputed tomographic scan of the orbits and paranasalsinuses performed at an outside institution in April 2009

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showed a 3.0 × 2.0 × 5.7 cm, heterogeneously enhancing,soft tissue mass in the left nasal cavity with associatedremodeling of the left lateral nasal wall and the bony septum.The bony middle and anterior turbinates appeared severelythinned or remodeled. The left osteomeatal complex wasobstructed by the mass at the left middle meatus and thehiatus semilunaris. There was no involvement of the leftorbit; however, the mass was obstructing the left nasallacrimal duct at the distal opening of the left inferior meatusof the nasal cavity. In July 2009, the patient underwent anendoscopic nasal cavity exploration, which showed a large,smooth-appearing mass filling approximately 80% of the leftnasal cavity. It obliterated and appeared to arise from the leftinferior turbinate without involvement of the middleturbinate. A biopsy obtained from the mass was initiallyinterpreted as a respiratory epithelial adenomatoid hamar-toma without evidence of malignancy. In September 2009,an endoscopic resection of the mass was performed. At thetime of surgery, the mass was noted to be very firm andaccommodated the dimensions of the nasal cavity. The masswas excised intact and submitted for pathologic examination.

Macroscopically, the specimen consisted of 3 separatepieces of pink-tan, firm, glistening, and rubbery tissueweighing 15.5 g in aggregate and ranging in size from 1.0 ×0.5 × 0.3 to 5.8 × 2.5 × 1.8 cm. There were small fragmentsof translucent and membranous-appearing bone attached tothe largest piece, the surface of which was focally hyperemic.The cut surfaces of each fragment appeared to have variablysized, smooth-walled, fluid-filled cysts surrounded by densefibrous tissue.

Histologic examination revealed an exuberant prolifera-tion of both epithelial and stromal elements. The epithelialcomponent consisted of a lobular proliferation of mostlyductal and scattered tubuloacinar structures within a fibrousstroma (Fig. A). These small, closely packed ductalstructures were lined by cuboidal epithelial cells withmoderately abundant, pale eosinophilic cytoplasm andrelatively bland-appearing, round nuclei containing incon-spicuous nucleoli (Fig. B). The acinar-type cells containedbrightly eosinophilic, intracytoplasmic, modified zymogengranules (Fig. C). No significant mitotic activity, necrosis, ordysplastic features were observed. In some areas, there wereprominent cystically dilated ducts that exhibited dense,periductal fibrosis and contained eosinophilic secretions(Fig. D). These ectatic ducts were lined by a markedlyattenuated epithelium and embedded within a relativelycellular, bland-appearing fibroblastic stroma (Fig. E).

Immunohistochemical staining was performed usingstandard immunoperoxidase techniques. The epithelialcomponent was uniformly positive for cytokeratin 7 andnegative for cytokeratin 20. Immunostains for cytokeratin5/6, p63, calponin, and smooth muscle actin (SMA)(Fig. F) highlighted the abluminal, myoepithelial cellssurrounding each of the ductal structures. In contrast,carcinoembryonic antigen and c-kit were positive in theluminal cells. Vimentin was positive in the fibroblastic

stromal component. No detectable staining was seen forglial fibrillary acidic protein.

Taking together the unique histopathologic findings andthe results of the immunohistochemical stains, a diagnosis ofSPCA was rendered. Because the mass was completelyresected, no further treatment was indicated. The patient hasbeen monitored for recurrence via annual nasopharyngosco-pies. Thirty-eight months after the resection of the sinonasalmass, the patient appears to be stable clinically with noevidence of recurrence or metastasis.

3. Discussion

Sclerosing polycystic adenosis is a rare, sclerosing lesionof the salivary glands that was first described by Smith et al[1] in 1996. The histologic features of SPCA are similar tofibrocystic changes of the breast and include lobularproliferation of ductal and acinar elements, cystically dilatedducts, and dense fibrosis [1]. Several cases of dysplasia andcarcinoma in situ of the ductal epithelium have been reported[4,5,9,11]. The cytologic features and the associatedcytologic diagnostic dilemmas of SPCA have also beendescribed [3]. Thus far, all cases of SPCA reported in theliterature have involved the salivary glands, most commonlythe parotid gland [1–14].

Although SPCA is generally believed to be a reactivelesion, Skalova et al [10] demonstrated a pattern of X-chromosome inactivation in 6 of 12 cases of SPCAindicating a nonrandom, clonal process suggestive of aneoplastic etiology. Further evidence of a possible neoplasticetiology was provided by a study demonstrating the presenceof Epstein-Barr virus in the lesional cells of SPCA byimmunohistochemistry and real-time polymerase chainreaction [15]. However, reported cases of SPCA have beenassociated with a favorable outcome; recurrence is possible,but metastasis has not been described [1,2,4–6,8,12,14].

The sinonasal tract is lined by respiratory mucosa andcontains seromucinous glands. Salivary gland tumors suchas adenoid cystic carcinoma and mucoepidermoid carci-noma are known to occur in the sinonasal tract. Thus, it isnot unreasonable to expect that other salivary glandlesions may occur in this location. The current case ofSPCA diagnosed on a mass lesion arising from the leftinferior turbinate is the first reported case of SPCA in thesinonasal tract.

If the histologic appearance of a sinonasal mass suggests adiagnosis of SPCA, the differential diagnostic considerationsmight include tumors with cystic or oncocytic features andbenign lesions such as respiratory epithelial adenomatoidhamartoma, nasal seromucinous hamartoma (microglandularadenosis), and inflammatory polyp. One diagnostic consid-eration is mucoepidermoid carcinoma, which may resembleSPCA in that it exhibits cystic change, mucous andsquamous cells, and desmoplastic stroma and inflammation.However, mucoepidermoid carcinoma may also contain

Fig. Sclerosing polycystic adenosis. A, Exuberant proliferation of ductal and tubuloacinar elements in a dense fibrous background(hematoxylin and eosin, original magnification ×40). B, Small, closely packed ductal structures lined by benign-appearing cuboidal epithelialcells (hematoxylin and eosin, original magnification ×200). C, Acinar-type cells containing brightly eosinophilic, intracytoplasmic, modifiedzymogen granules (hematoxylin and eosin, original magnification ×200). D, Prominent cystically dilated ducts with intraluminal eosinophilicsecretions and dense, periductal fibrosis (hematoxylin and eosin, original magnification ×40). E, Ectatic ducts lined by markedly attenuatedepithelium embedded within a relatively cellular, bland-appearing fibroblastic stroma (hematoxylin and eosin, original magnification ×200). F,Immunohistochemical stain for SMA highlighted the abluminal, myoepithelial cells surrounding each of the ductal structures (originalmagnification ×200).

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features such as necrosis, infiltration, and increased mitoticactivity and nuclear atypia, which should be absent orminimal in SPCA. Distinguishing between a low-gradeadenocarcinoma and SPCA may present a diagnosticdilemma in light of the exuberant ductal proliferation butcan be resolved by recognition of the lobular configurationof the latter. Furthermore, immunohistochemical stains formyoepithelial cells such as SMA, calponin, p63, andcytokeratin 5/6 will highlight the abluminal cells of SPCAand will be absent in low-grade adenocarcinoma. Sinona-sal hamartomas such as respiratory epithelial adenomatoidhamartoma and seromucinous hamartoma may containnumerous glands and stroma with a variety of mesenchy-mal elements. The former contains glands that have aciliated respiratory epithelium surrounded by a thickbasement membrane. The latter exhibits seromucinousglands, which, in contrast to SPCA, lack a myoepithelialcell layer [16,17]. As such, immunostains for myoepithe-lial cells are a useful diagnostic adjunct in distinguishingbetween these 2 differential diagnostic considerations,particularly in small biopsy specimens. Inflammatorypolyps have an edematous stroma with inflammation andmay show prominent seromucinous glands. In contrastwith the aforementioned benign lesions, the ducts inSPCA show frequent apocrine and sebaceous metaplasia.Moreover, the ducts and acini of SPCA generally have alobular configuration.

As more cases of SPCA involving the sinonasal tract arereported along with follow-up data, more informationregarding the behavior of SPCA in this location will beobtained. However, we speculate that SPCA in thesinonasal tract has a pathogenesis similar to SPCA in thesalivary glands, and therefore, SPCA in the sinonasal tractmay recur but should have a favorable outcome. Thecurrent case shows no evidence of recurrence or metastaticdisease 38 months after resection. When more data becomeavailable, the exact behavior of SPCA arising in thesinonasal tract can be determined.

Since the first description by Smith et al [1] in 1996,SPCA has been increasingly diagnosed in salivary glands.In a similar fashion, as SPCA becomes more recognizedin other locations such as the sinonasal tract, thediagnosis of SPCA may be made more often in thefuture. As more pathologists become familiar with SPCA,the diagnostic accuracy of lesions of the sinonasal tractwill be enhanced.

References

[1] Smith BC, Ellis GL, Slater LJ, et al. Sclerosing polycystic adenosis ofmajor salivary glands. A clinicopathologic analysis of nine cases. Am JSurg Pathol 1996;20:161-70.

[2] Bharadwaj G, Nawroz I, O'Regan B. Sclerosing polycystic adenosis ofthe parotid gland. Br J Oral Maxillofac Surg 2007;45:74-6.

[3] Etit D, Pilch BZ, Osgood R, et al. Fine-needle aspiration biopsyfindings in sclerosing polycystic adenosis of the parotid gland. DiagnCytopathol 2007;35:444-7.

[4] Fulciniti F, Losito NS, Ionna F, et al. Sclerosing polycystic adenosis of theparotid gland: report of one case diagnosed by fine-needle cytology within situ malignant transformation. Diagn Cytopathol 2010;38:368-73.

[5] Gnepp DR. Sclerosing polycystic adenosis of the salivary gland: alesion that may be associated with dysplasia and carcinoma in situ.Adv Anat Pathol 2003;10:218-22.

[6] Gnepp DR, Wang LJ, Brandwein-Gensler M, et al. Sclerosingpolycystic adenosis of the salivary gland: a report of 16 cases. Am JSurg Pathol 2006;30:154-64.

[7] Imamura Y, Morishita T, Kawakami M, et al. Sclerosing polycysticadenosis of the left parotid gland: report of a case with fine needleaspiration cytology. Acta Cytol 2004;48:569-73.

[8] Perottino F, Barnoud R, Ambrun A, et al. Sclerosing polycysticadenosis of the parotid gland: diagnosis and management. Eur AnnOtorhinolaryngol Head Neck Dis 2010;127:20-2.

[9] Petersson F, Tan PH, Hwang JS. Sclerosing polycystic adenosis of theparotid gland: report of a bifocal, paucicystic variant with ductalcarcinoma in situ and pronounced stromal distortion mimickinginvasive carcinoma. Head Neck Pathol 2011;5:188-92.

[10] Skalova A, Gnepp DR, Simpson RH, et al. Clonal nature of sclerosingpolycystic adenosis of salivary glands demonstrated by using thepolymorphism of the human androgen receptor (HUMARA) locus as amarker. Am J Surg Pathol 2006;30:939-44.

[11] Skalova A, Michal M, Simpson RH, et al. Sclerosing polycysticadenosis of parotid gland with dysplasia and ductal carcinoma in situ.Report of three cases with immunohistochemical and ultrastructuralexamination. Virchows Arch 2002;440:29-35.

[12] Gurgel CA, Freitas VS, Ramos EA, et al. Sclerosing polycysticadenosis of the minor salivary gland: case report. Braz J Otorhinolar-yngol 2010;76:272.

[13] Meer S, Altini M. Sclerosing polycystic adenosis of the buccalmucosa. Head Neck Pathol 2008;2:31-5.

[14] Noonan VL, Kalmar JR, Allen CM, et al. Sclerosing polycysticadenosis of minor salivary glands: report of three cases and review ofthe literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod2007;104:516-20.

[15] Swelam WM. The pathogenic role of Epstein-Barr virus (EBV) insclerosing polycystic adenosis. Pathol Res Pract 2010;206:565-71.

[16] Weinreb I, Gnepp DR, Laver NM, et al. Seromucinous hamartomas: aclinicopathological study of a sinonasal glandular lesion lackingmyoepithelial cells. Histopathology 2009;54:205-13.

[17] Ambrosini-Spaltro A, Morandi L, Spagnolo DV, et al. Nasal seromuci-nous hamartoma (microglandular adenosis of the nose): a morphologicaland molecular study of five cases. Virchows Arch 2010;457:727-34.