CASE REPORT Eben L. Rosenthal, MD, Section Editor

SIGNET RING CARCINOMA PAROTID GLAND: A CASE REPORT

Meeta Singh, MD,1 Nita Khurana, MD, DNB,1 Rachna Wadhwa, MD,1 Achal Gulati, MD2

1Department of Pathology, Maulana Azad Medical College and Lok Nayak Hospital, Bahadur Shah Zafar Marg,New Delhi, India. E-mail: meetamamc@gmail.com

2Department of Otolaryngology, Maulana Azad Medical College and Lok Nayak Hospital, Bahadur Shah ZafarMarg, New Delhi, India

Accepted 19 February 2010Published online 19 May 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/hed.21435

Abstract: Background. Signet ring adenocarcinoma is a

recently characterized entity occurring in the minor salivary

glands. All reported cases have occurred in minor salivary

gland. Pure signet ring adenocarcinoma of a major salivary

gland has not been reported in the literature.

Methods. A 38-year-old woman presented with a mass in

the parotid region. Microscopy showed signet ring cells posi-

tive for mucicarmine. Immunohistochemistry showed cytokera-

tin and focal smooth muscle actin (SMA) positivity; an

exhaustive search for primary elsewhere did not reveal any

suspicious focus.

Results. A diagnosis of low-grade signet ring adenocarci-

noma of the parotid gland was made. On 6-month follow-up

the patient was alive and well.

Conclusions. The present case highlights a rare occur-

rence of this tumor in the parotid gland, which until now was

labeled as a tumor exclusive to minor salivary glands. Thus

this entity should be kept as a differential while investigating

mucinous tumors of parotid. VVC 2010 Wiley Periodicals, Inc.

Head Neck 33: 1656–1659, 2011

Keywords: signet ring; adenocarcinoma; parotid; mucicarmine;

cytokeratin

Signet ring adenocarcinoma is a recently characterized

entity occurring in the minor salivary glands. The mean

age of presentation is 56.4 years, with a female prepon-

derance.1 All reported cases have occurred in the minor

salivary gland of the oral cavity or oropharynx in the

form of exophytic growth fixed to underlying tissue.1

Pure signet ring adenocarcinoma of a major salivary

gland has not been reported in the literature before.

We document the first reported example ofthis tumor in a parotid gland of a 38-year-oldwoman, who had a long-standing history of amass in parotid region which was misdiagnosedas pleomorphic adenoma clinically.

We also present the detailed microscopic fea-tures as well as confirmatory cytochemistry andimmunohistochemistry of this case followed by adiscussion on tumors with signet ring like fea-tures in salivary glands with focus on major sal-ivary glands.

CASE REPORT

A 38-year-old woman presented with a mass inthe parotid region on her right side, which hadbeen slow growing for the previous year andassociated with pain. On examination, the swel-ling was 3 � 2.5 cm, nodular, and nontender,and the overlying skin was normal, with a slightrestriction of mobility of the temperomandibularjoint. The swelling was vaguely palpable per-orally, with a normal overlying mucosa. Therewas no associated cervical lymphadenopathy,and the oral cavity was unremarkable. A clinicaldiagnosis of pleomorphic adenoma was made.The fine-needle aspiration report was inconclu-sive, so the mass was excised along with 2-cmmargin of normal salivary gland tissue. Periop-eratively the mass was firm, well circumscribed,and hemorrhagic.

Grossly, the tissue received showed part of anormal salivary gland surrounding a tumor nod-ule measuring 3 � 2 � 1.5 cm, well encapsu-lated; the cut section was grayish white, firm,with areas of hemorrhage.

Microscopically, the tumor was hypercellular,with cells predominantly present in solid sheets(Figure 1). Although the tumor was well encap-sulated, at places an invasive pattern was seen,with cells in interconnected cords and parallelstrands, although focally single cells were pres-ent, interspersed in hyalinized stroma (Figure1). The individual cells were large and showed alarge cytoplasmic mucinous globule displacing

Correspondence to: M. Singh

VVC 2010 Wiley Periodicals, Inc.

1656 Signet Ring Carcinoma Parotid Gland HEAD & NECK—DOI 10.1002/hed November 2011

the nucleus to 1 pole like a signet ring(Figure 2). These cells were more or less mono-morphic, with only slight variation in size withsome showing several small vacuoles. There wasminimal nuclear pleomorphism and rare atypi-cal mitosis. There was focal preservation ofmyoepithelial cells, which appeared attenuated,and stroma showed increased vascularity. Thecapsule was thick, fibrous (Figure 1), andshowed a focal area of infiltration, although notbeyond the capsule. Exhaustive multiple sec-tions from the tumor failed to reveal any otherpattern with the absence of extracellular muci-nous areas, papillary, oncocytic, gland and ductformation or intraductal component, cribriformareas, or perineural invasion.

Considering this pattern, an exhaustivesearch for the possibility of a primary elsewherewas made clinicoradiologically, including thegastrointestinal tract, breast, ovary, bladder,lungs, pancreas, and liver, and no suspiciousfocus was found anywhere.

The intracellular mucin was confirmed bybright pink positivity with mucicarmine (Figure2, inset). Immunohistochemistry, performed bythe avidin-biotin method with 3,30-diaminobenzi-dine (DAB) as chromogen, showed cells stronglypositive for anti-cytokeratin (CK cocktail) (Fig-

ure 3). The attenuated myoepithelial cells weredelineated with smooth muscle actin (SMA)immunostain (Figure 3, inset), although S-100,thyroglobulin, A-fetoprotein (AFP), carcinoem-bryonic antigen (CEA), and CK-20 were nega-tive. Serum CA-125 and CA 19-9 were negative.Thus, a final diagnosis of low-grade signet ringadenocarcinoma of parotid gland was made.

The patient was kept under close follow-upand has shown no signs of recurrence for thepast 6 months.

DISCUSSION

Mucin-secreting adenocarcinomas of the salivarygland are extremely rare tumors, unlike theircounterparts in the gastrointestinal (GI) tract,and form a diverse group of neoplasms. Signetring adenocarcinoma salivary gland (SRCA) is adistinct type of mucin-secreting adenocarcinoma,characteristically described in minor salivaryglands of the oropharyngeal region.3,11,12 It hasnot been described in major salivary glands so far.

With respect to the major salivary glands,mucin-secreting adenocarcinomas, not otherwisespecified, are well known.2,4,6,8,10 Although insome of these studies occasional signet ring cellswere observed, the prominent feature was thatof pools of mucin separated by fibrous septa inwhich groups of tumor cells appeared to float

FIGURE 1. Tumor showing thick capsule and pattern of

arrangement of cells in sheets, strands, and cords. Part of nor-

mal salivary gland is also visualized (hematoxylin–eosin stain,

original magnification �100). [Color figure can be viewed in the

online issue, which is available at wileyonlinelibrary.com.]

FIGURE 2. Cells with characteristic signet ring appearance,

mild pleomorphism (hematoxylin–eosin stain, original magnifica-

tion �400). Inset shows bright pink staining with mucicarmine

(mucicarmine, original magnification �400). [Color figure can be

viewed in the online issue, which is available at

wileyonlinelibrary.com.]

Signet Ring Carcinoma Parotid Gland HEAD & NECK—DOI 10.1002/hed November 2011 1657

with cells exhibiting mild to moderate pleomor-phism. This is in contrast to our case, whichshowed the absence of mucin pools, with onlyone cell type (ie, signet ring cells present insheets and cords with minimal pleomorphism),similar to the morphology described by Ghan-noum et al,3 who studied 7 cases of SRCAs inminor salivary glands. Another interesting case,described by Horn et al,5 was that of mucin-secreting adenocarcinoma in the parotid glandthat contained pleomorphic cells, with only occa-sional signet ring cells without mucin pools andlater developed lymph node and brain metasta-sis, which is dissimilar to our case clinically andmorphologically because this case showed nometastasis, similar to SRCAs of minor salivaryglands. They can also be confused with mucoepi-dermoid carcinomas, which are characterized bythe presence of epidermoid cells, intermediatecells, and clear cells, which are different fromsignet ring cells described in this case.

Other than mucin-secreting adenocarcinoma,signet ring morphology in the parotid gland hasalso been described by Michal et al,7 who reporteda rare entity called oncocytic cystadenoma with aprominent signet ring cell feature. Although thiscase showed prominent signet ring cells withbland morphology like ours, these cells coexistedwith oncocytic cells and were negative on mucicar-mine and CK immunostain. Similar vacuolated

cells can also be observed in 10% of acinic cell car-cinomas, which have ultrastructurally proven tobe of intercalated duct differentiation and negativefor CK immunostain. Rarely, signet ring lympho-mas are also described in salivary glands, buthave a totally different morphological and immu-nohistochemical profile.9 Metastasis from otherorgans harboring malignancy with similar mor-phology was ruled out clinicoradiologically and bynegativity for thyroglobulin, AFP, CEA, and CK-20 with serology negative for CA-125 and CA 19-9.

As far as SMA positivity in this tumor is con-cerned, it highlighted attenuated myoepithelialcells present at some places, and because of thisfeature a differential of clear cell epithelial-myoepithelial carcinoma was also kept. How-ever, it was excluded by the absence of charac-teristic morphology, negativity of S-100, and thepresence of signet ring cells, which are differentfrom clear myoepithelial cells.

In terms of prognosis, signet ring carcinomasof salivary glands surprisingly behave as low-grade malignant neoplasms with no recurrenceor metastasis after excision; this contrastsgreatly with signet ring carcinomas of othersites.1 The present case shares similarities witha case series on signet ring adenocarcinomas ofminor salivary glands,3 in terms of both treat-ment (ie, excision alone) and an unremarkablepostoperative period. A recently described signetring adenocarcinoma in oropharynx, however,showed bilateral lymph node involvement withextracapsular spread and was treated with exci-sion, bilateral neck dissection, and postoperativeradiotherapy.11 The present number of casesreported are inadequate for reaching any con-clusion, and larger case series are required toconfidently comment on the biological behaviorand, thus, the natural history of these tumors.

To summarize, the present case highlightsa rare occurrence of SRCA in the parotidgland, which until now was labeled as a tumorexclusive to minor salivary glands. Thus this en-tity should be kept as a differential whileinvestigating mucinous tumors of parotid, bothby the clinician and pathologist, because itcarries different treatments and prognosticimplications.

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FIGURE 3. Cells strongly positive with cytokeratin. Inset show-

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chromogen, original magnification �400). [Color figure can be

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wileyonlinelibrary.com.]

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