Primary carcinoma of the extrahepatic biliary tree has an incidence of 0.14% of all malignancies with commonest site as the CBD (40.1%) whereas primary carcinoma of cystic duct is extremely rare [5, 6]. The incidence of primary carcinoma of cystic duct in autopsy studies was found to be 0.03–0.05% [7]. The primary carcinoma of cystic duct has been found to have male preponderance with no specific sex predilection and the average age of presentation was 65 years (range, 38–79 years) [2, 4–6, 8, 9] Gallstones are not associated with all cases, being found in about 25% of the cases [2, 5, 10], and 48 and 37% in two other series [2, 9] which is in stark contrast to 75–90% reported for classical gall bladder carcinoma. It is proved that inflammation of the biliary duct epithelium due to irritation from reflux and stasis of pancreatic juice and bile leads to malignancy over a period of time [2, 7, 10, 11]. However, the risk factors for carcinoma of cystic duct are unclear.

Its clinical presentation is non-specific and mostly is similar to biliary calculus disease [2, 6, 7, 11]. The symptoms may develop earlier than GB cancer. The main symptom was abdominal pain and jaundice, both being equally distributed [1, 2, 4, 5, 8] According to Baraka et al. in 33 reported cases 81% presented with right upper quadrant abdominal pain, 41% with abdominal mass, and four cases with obstructive jaundice [6]. Gallbladder was found to be hydropic in 86 and 93% cases [2, 5]. The tumour is either discovered at laparotomy or on histopathological examination of the specimen [1, 2, 4–6, 11]. In none of the cases reported, a preoperative diagnosis was made. In our case too, patient had history of transient jaundice with upper abdominal pain and hydrops of gallbladder and final diagnosis was made on histopathological examination. Neoplasm of the cystic duct can be suspected in patients presenting with distended gallbladder likely due to cystic duct obstruction without evidence of stone impaction in the cystic duct.

Different staging systems for various cancer have been described worldwide but to date no diagnostic or staging system have been established for carcinoma of cystic duct which could be uniform and applicable to all cases [1–5]. In 1951, Farrar’s first described diagnostic criteria for primary carcinoma of cystic duct [1] (Table 1).

Farrar criteria is strict and cannot differentiate advanced tumors as patients may present in different stages of the disease and true cystic duct carcinoma becomes a non-cystic duct carcinoma once it advanced beyond cystic duct [1, 2]. The new classification(s) [3–5] that defines carcinoma of cystic duct as a tumor with its center located in the cystic duct appears more practical as mostly reported cases of carcinoma of cystic duct were advanced. The cystic duct is a short structure, which lacks a proper muscle layer and consists of a thin fibro-muscular layer and adventitia. Extra hepatic bile ducts are lined by a layer of tall columnar epithelium which extends from the mucosal lining through the entire wall to form glands in the outer coats of the ducts. Thin-walled ducts, the presence of glands in the outer coats, the rich lymphatic network and nerve supply apparently facilitate spread of the tumor to periductal structures [12]. The histology of the cystic duct comprises a transient pattern from gallbladder to bile duct, indicating that there is a watershed in the cystic duct that separates the features of the gallbladder from those of the bile duct [4].

The classically described carcinoma of cystic duct is very rare and is attributed to its strict definition [1] in which a tumor is restricted to the cystic duct, and if new definitions [3–5] are properly applied then more cases can come up. Most of the tumors were microscopically well-differentiated adenocarcinoma, but small cell carcinoma, carcinoid tumor, mucin-producing carcinoma of cystic duct also have been reported [3, 9, 13]. Bile duct invasion is relatively rare [1, 11, 14, 15]. The incidence of lymph node metastasis is (0–40%) in patients with carcinoma of cystic duct which is lower than those with extrahepatic bile duct (about 50%) or GB cancer (40–80%) [2, 4, 11, 15].

The early development of symptoms due to obstruction of the cystic duct, mimicking signs and symptoms of gallbladder disease, slow growth, and late metastasis favor a better prognosis in patients with carcinoma of cystic duct as compared to extrahepatic bile duct or GB cancer [2–4, 6, 9, 11, 14, 15]. The perineural invasion is one of the most significant prognostic risk factor in malignancies of biliary tree. The incidence of perineural invasion in extrahepatic bile duct carcinoma is 85–93% and in gallbladder carcinoma is 24–72% [16]. High frequencies of perineural (87%) and lymphatic invasion (83.8%) were observed by Ozden et al., and similar findings were reported by Nakata et al. as perineural (73.3%) and lymphatic invasion (80%) [2, 5]. Perineural and the microscopic vascular invasion were more frequent in the HH type than in the CC type whereas lymph node metastasis and lymphatic permeation was similar in both [4].

In our case, the tumor was type 1 of Kim’s classification (confined within the cystic duct), CC type of Yokohama’s classification (in cystic duct and towards confluence of the cystic duct) and type I of Nakata’s classification (located wholly within the cystic duct). A meta-analysis conducted by Kim et al. of the previous case reports regarding clinical and pathological characteristics and patient survival found that patients with type I cancer had significantly longer survival compared to type II or III cancer (p = 0.018, p = 0.03). However, there was no significant difference between patients with type II cancer and type III cancer (p = 0.989) [3]. The survival rate tends to be higher for patients with the CC type than for those with the HH type (p = 0.064). The CC type lesions were more common in males, and female sex was predominant for the HH type [4]. It is concluded that carcinomas of cystic duct extending beyond the cystic duct are more aggressive and associated with a poorer prognosis [4, 15].

The recommended treatment is radical surgery comprising of cholecystectomy with non-anatomical gallbladder fossa resection and excision of extrahepatic bile duct with regional lymphadenectomy.^3,5,9,10.11 The average tumor size was 25–27 mm with range of 4–60 mm [2, 5]. Postoperative adjuvant radiation therapy can be considered in cases of advanced carcinoma of cystic duct particularly those with positive surgical margin [3, 9].

The average survival was reported to be 27.2 months while that of gallbladder carcinoma was only 5.8 months and of other extrahepatic biliary ducts 3.2-11.4 months [3, 15]. Nakata et al. reported 5-year survival rate of 40% and median survival of 2.4 years. The survival was significantly longer in patients with type I as compared to type IV (p=0.05) whereas no significant differences in survival rate among patients with types II, III, and IV cystic duct carcinoma were found [5]. The median overall survivals for patients with HH type and CC type were 11.9 and 45.8 months, respectively [3]. Advances in imaging and molecular basis of disease have led to better understanding of this tumor however more number of cases evaluation will provide significance.