Degenerative Signet Ring Cell Change in a Bile Duct Brushing.

Signet-ring cell change (SRCC) of epithelium, sometimes referred to as pseudo-signet ring cells or benign or non-neoplastic signet ring cells has been described in multiple organs. It typically represents a reactive and degenerative epithelial change in the setting of acute inflammation and/or ischemia. SRCC has significant cytologic overlap with signet ring cell adenocarcinoma (SRCA), making it a potential diagnostic pitfall.

A 41-year-old male with no history of malignancy and suspected biliary stones presented for endoscopic retrograde cholangiopancreatography. No stones or lesions were identified. However, bile duct brushing cytology was performed. ThinPrep and cell block slides revealed a cellular specimen with an atypical population of glandular cells [Figure 1a and b]. The cells were loosely cohesive and had moderately abundant, vacuolated cytoplasm. Moderate nuclear pleomorphism was present. Many of the cells had crescent-shaped nuclei pushed to the periphery by mucinous cytoplasmic material (i.e. signet ring cell morphology).

Figure 1

(a) - Reactive ductal epithelium (bottom left) and a second population of large cells with abundant cytoplasm and disorganized nuclei. (Hematoxylin and eosin [H and E], 400×). (b) - Numerous crescent-shaped nuclei pushed to the cellular periphery by vacuolated cytoplasm are present. (Papanicolaou stain, 400×). (c) - Cholecystectomy revealed acute cholecystitis with mucosal ulceration and sloughing of degenerating surface epithelium. (H and E, 100×). (d) - High power view of the sloughed gallbladder epithelium with degenerative signet ring cell change. (H and E, 400×)

The patient also showed signs and symptoms of acute cholecystitis and underwent cholecystectomy during workup of the bile duct brushing. No gallstones, masses, or wall-thickening were identified. However, the gallbladder was filled with mucopurulent bilious fluid. Histologic sectioning of the gallbladder showed diffuse, transmural involvement by severe acute and chronic cholecystitis [Figure 1c]. Significant mucosal ulceration was noted and degenerative changes were seen in the retained lining epithelium, including diffuse sloughing of the surface epithelium exhibiting SRCC. No malignancy was present. The degenerative signet ring-type cells seen in the gallbladder were essentially identical to the cells seen in the cytologic specimen, demonstrating the benign nature of the bile duct brushing cytology [Figure 1d].

Signet ring cells are relatively uncommon in cytologic specimens but are strongly associated with malignancy when present, most commonly from gastrointestinal tract or breast primary adenocarcinomas. A study at one institution found that 78% of cytologic cases with cells exhibiting signet ring cell morphology were malignant, predominantly adenocarcinomas.[1] Non-neoplastic sources of signet ring-type cells in cytologic specimens included reactive/degenerative epithelial cells and goblet cells, as well as histiocytes and mesothelial cells.[12]

SRCC has been reported most commonly in the gastrointestinal tract, particularly in the setting of ischemic colitis and pseudomembranous colitis, and in the endocervix in the setting of previously cauterized polyps.[3] Acute cholecystitis and erosive cholangitis have also been associated with SRCC in the gallbladder and bile duct, respectively.[345]

Differentiation of degenerative SRCC from SRCA is difficult. Both can present without a mass lesion. The presence or absence of invasion cannot be well assessed on exfoliative cytology, and there is significant cytomorphologic overlap between SRCC and SRCA. In SRCC, nuclear atypia is often mild. However, cells from SRCA can also be deceptively bland and may be mistaken for histiocytes, reactive mesothelial cells, or reactive/reparative epithelial changes on exfoliative cytologic specimens.[12] When present, severe nuclear atypia suggests SRCA. Nuclear atypia was mild to moderate in this case. Histologically, the pattern of cellular growth is helpful in differentiating SRCC and SRCA. SRCC presents specifically at the superficial mucosa in degenerating, exfoliating clusters [Figures 1c and d], whereas SRCA shows infiltrating growth and desmoplasia of the underlying stroma.[3456]

Although the signet ring-type cells present in this specimen readily exfoliated on brushing cytology, one feature hinting at their benign nature is that cohesion within groups was largely maintained [Figure 1b]. SRCC tends to maintain e-cadherin expression, whereas loss of cohesion is a hallmark of SRCA.[6]

To my knowledge, degenerative signet ring-type cells have not previously been described in bile duct brushing cytology. Although most commonly seen in the gastrointestinal tract, SRCC can occur in the setting of acute inflammation and tissue ischemia of any glandular surface. Awareness of SRCC is critical to prevent over diagnosis of SRCA in directed epithelial brushing cytology specimens. SRCC should be considered when epithelial cells with signet ring morphology are identified in the presence of acute inflammatory and/or ischemic changes, and in the absence of severe nuclear atypia or loss of cohesion. Care should be taken to avoid over diagnosing SRCC, particularly in patients for whom there is a low clinical index of suspicion for malignancy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.