Primary Langerhans Cell Histiocytosis of the Extrahepatic Bile Duct Occurring in an Adult Patient.
A 62-year-old female patient was referred to our institution for further diagnostic workup of elevated liver enzymes and incidental cholelithiasis. She complained of worsening jaundice, nausea and vomiting, dark urine, and a 25-pound weight loss at the time of admission. Liver function results were as follows: aspartate aminotransferase 43 U/L and alanine aminotransferase 53 U/L, alkaline phosphatase 442 U/L, albumin 3.2 g/dL, bilirubin total 2.5 mg/dL, and bilirubin direct 1.5 mg/dL. An endoscopic retrograde cholangiopancreatography showed strictures of the common bile duct suggestive of primary sclerosing cholangitis. A contrast-enhanced computed tomography scan (Figure 1) revealed an ill-defined, low-attenuating soft tissue mass in the porta hepatis with biliary duct dilatation, but no intrahepatic mass was identified. Based on these findings, a preoperative diagnosis of cholangiocarcinoma secondary to primary sclerosing cholangitis was made. The patient underwent a common bile duct resection, cholecystectomy, and Roux-en-Y hepaticojejunostomy. The mass was completely removed and sent to pathology for confirmatory diagnosis. Histologic sections of the left and the right bile ducts showed a histiocytic cell proliferation that consisted of mononuclear bean-shaped cells with cleaved nuclei and abundant cytoplasm admixed with eosinophils (Figure 2a, 2b). Sections of the adjacent liver showed variable bile duct proliferation, focal bridging and periductal fibrosis, and cholestasis. Immunohistochemistry revealed neoplastic cells that were positive for S100 (Figure 2c), CD1a (Figure 2d), CD68, CD14, and lysozyme. Electron microscopy of the tumor cells demonstrated the presence of Birbeck granules (Figure 2e) in the majority of histiocytes examined. These findings confirmed the diagnosis of LCH. The patient underwent a whole-body imaging to look for other areas of disease involvement, but the studies were negative. The patient received adjuvant chemotherapy with 5 courses of cladribine and was disease-free for 14 months after which she developed bacteremia due to a polymicrobial biliary infection from a chronic indwelling biliary drain. On admission, imaging studies did not reveal any evidence of malignancy. The patient went into septic shock, and despite therapeutic measures with antibiotics, vasopressor support, and volume resuscitation, she expired. An institutional review board waiver of consent was obtained for publishing the case report.
LCH consists of a constellation of clinical presentations, which include Letterer-Siwe syndrome, a multisystem disease of young children characterized by cutaneous lesions containing infiltrates of Langerhans cells and a poor prognosis; eosinophilic granuloma, a solitary bone lesion; and Hand-Schuller-Christian disease that manifests as a characteristic triad of cranial bone lesions, diabetes insipidus, and exophthalmos (2). LCH can affect any organ or system in the body, but those more commonly affected are bone (80%), skin (33%), pituitary gland (25%), lungs (15%), liver (15%), the hematopoietic system (15%), lymph nodes (5%-10%), and the central nervous system excluding the pituitary gland (2%-4%) (4). The natural history of the disease is also extremely variable, ranging from a self-remitting lesion to a disease involving several organs with life-threatening consequences.
LCH involvement of the bile duct can occur, but it usually presents in the disseminated form of the disease and the prognosis is very poor (5,6). LCH of the bile duct can present with progressive destruction leading to sclerosing cholangitis and eventually to secondary biliary cirrhosis (7-9). Primary LCH of the extrahepatic bile duct is very rare. Prior to our report, only one case has been reported in a 2.5-year-old female patient (10). A review of both cases showed that primary LCH of the bile duct presents as a solitary mass with clinical signs and symptoms of obstructive jaundice. Common sequelae of the mass appear to be sclerosing cholangitis, and both were diagnosed on a cholangiogram. Some reports suggest that the presence of sclerosing cholangitis, especially in children, should raise a suspicion for LCH (11,12). However, these studies included cases of disseminated LCH involving the hepatobiliary system, and involvement of the extrahepatic bile duct in these cases was rare. The key to a definitive diagnosis of LCH of the bile duct depends on the morphologic identification of abnormal proliferation of mononuclear cells with bean-shaped cleaved nuclei, which are derived from myeloid progenitor cells of the bone marrow (1). Similar to Langerhans cells located in the skin, they express histiocytic markers such as S100, CD1a, and CD68 and contain Birbeck granules, which are rod-shaped intracytoplasmic organelles best demonstrated on electron microscopy.
Treatment of LCH depends on the extent of the disease and can range from observation, surgery, and radiotherapy to multimodal chemotherapy. However, the precise treatment of primary LCH of the bile duct remains unknown due to limited data. Successful treatment with orthotropic liver transplantation was demonstrated by Finn and Jaffe (10) in their 2.5-year-old patient; however, the long-term effect of the procedure was not determined. Although our patient was successfully treated with surgical resection of the common bile duct with biliary bypass and post-adjuvant chemotherapy with cladribine, she died from complications of sepsis. Therefore, more insight is needed to determine the best treatment of LCH confined to the extrahepatic bile duct.
In conclusion, LCH confined to the extrahepatic bile duct is a rare phenomenon that is challenging to diagnose both by the clinician and by the pathologist. A high clinical suspicion should have been raised in our adult female patient with sclerosing cholangitis with a solitary biliary mass. Early diagnosis and treatment is needed to improve the clinical outcome.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: No financial disclosure was declared by the authors.
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Ifeyinwa E. Obiorah, Alicia Henao Velasquez, Bhaskar Kallakury, Metin Ozdemirli
Department of Pathology, Medstar Georgetown University Hospital, Washington, USA
Address for Correspondence: Dr. Ifeyinwa E. Obiorah, Department of Pathology, Georgetown University Medical Center, Washington, USA
Phone: 2023843639 e-mail: Ifeyinwa.email@example.com ORCID ID: orcid.org/0000-0001-6285-7382
Received: 18 December 2017 Accepted: 2 March 2018 * DOI: 10.4274/balkanmedj.2017.1730
Cite this article as:
Obiorah IE, Henao Velasquez A, Kallakury B, Ozdemirli M. Primary Langerhans Cell Histiocytosis of the Extrahepatic Bile Duct Occurring in an Adult Patient. Balkan Med J 2018;35:437-9
TABLE 1. Reported cases of primary Langerhans cell histiocytosis of the biliary system Case Age Sex Clinical presentation Clinical Focality of (years) association the mass 1 2.5 Female Obstructive jaundice, Primary Solitary (10) hepatosplenomegaly, sclerosing ascites, pruritus cholangitis Our 62 Female Obstructive jaundice, Primary Solitary case nausea and vomiting, sclerosing dark urine, weight cholangitis loss Case Positive Treatment Recurrences Follow-up immunochemistry /metastasis (months) markers 1 CD1a, S100 Liver None Alive, 2 (10) transplantation years Our CD1a, S100, CD68 Common bile duct None Died of case resection+cladribine sepsis, 14 months
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|Title Annotation:||Case Report|
|Author:||Obiorah, Ifeyinwa E.; Velasquez, Alicia Henao; Kallakury, Bhaskar; Ozdemirli, Metin|
|Publication:||Balkan Medical Journal|
|Article Type:||Clinical report|
|Date:||Nov 1, 2018|
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