Diagnosis of Langerhans cell histiocytosis via percutaneous liver biopsy

doi:10.21203/rs.3.rs-5316467/v1

Download PDF

Research Article

Diagnosis of Langerhans cell histiocytosis via percutaneous liver biopsy

https://doi.org/10.21203/rs.3.rs-5316467/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background: The aims were to assess the clinical and histopathological characteristics of Langerhans cell histiocytosis (LCH) based on percutaneous liver biopsy and to improve the technique’s diagnostic accuracy.

Methods: Data from seven patients were collected. The clinicopathological features and immunophenotypes of hepatic LCH in the biopsied tissues were evaluated .

Results: Five men and two women (median age: 21 years) were included. The clinical presentations and imaging findings were unremarkable. In terms of the histological findings, multifocal and solitary lesions were detected in six patients and one patient, respectively. All lesions were located in the portal area and exhibited either enlarged or normal portal tracts. In four patients, Langerhans cells (LCs) were distributed either in clusters or scattered among mixed populations of inflammatory cells.LC invasion of the bile duct epithelium was detected in all but one patient; that individual presented with sclerosing cholangitis (SC) in the absence of LCs. One patient had a similar inflammatory myofibroblastic tumor (IMT) or inflammatory pseudotumor-like follicular dendritic cell (FDC) tumor. One patient had suppurative cholangitis with abscess formation, accompanied by a small degree of LC invasion into the bile duct epithelium.

Conclusions: The morphology of liver LCHs varied among patients. Bile duct epithelial damage accompanied by eosinophilic infiltration, a history of extrahepatic LCH, or central diabetes insipidus are clues that LCH may be present; however, H&E staining and IHC are crucial for its diagnosis. LCH should be differentiated from hepatic parasitic infections, primary SC, inflammatory pseudotumor-like FDC tumors, and inflammatory myofibroblastoma.

Langerhans cell histiocytosis

sclerosing cholangitis

liver

percutaneous biopsy

Langerhans cell histiocytosis (LCH) is a rare disease of unknown etiology with an annual prevalence of 2–5 cases per million individuals. LCH is primarily characterized by the abnormal proliferation of Langerhans cells in combination with enhanced cellular infiltration. LCH usually affects various organ systems in children and young adults, resulting in diverse clinical manifestations. Depending on the number of organs/systems involved, LCH can be classified as either single-system LCH or multisystem LCH (MS-LCH). Less than 30% of all LCH cases are classified as MS-LCH [1]. LCH often occurs in the bone, skin, and lymph nodes, and hepatic manifestations are relatively rare, occurring in just 7–15% of all LCH cases [2–6], and are usually present in disseminated disease states [7, 8]. Most of the studies involving hepatic LCH have been single case reports with an emphasis on treatment and imaging. In addition to its rarity, the ability to properly identify hepatic LCH is clinically important because of its remarkable prognostic value and unique pathological characteristics. The first aim of the present study was to retrospectively collect and analyze data from seven patients with LCH of the liver, including three cases involving the liver alone; the second aim was to analyze percutaneous liver biopsy samples collected from these patients to identify specific histopathological features that would facilitate immunophenotyping and improve clinical diagnosis.

Patient selection and ethical approval

The pathology records from patients who had received treatment at our hospital from 2013 to 2022 were retrospectively searched to identify seven patients who had been diagnosed with hepatic LCH. This study was approved by the Third Affiliated Hospital of Sun Yat-sen University Review Board.

Histology and immunohistochemistry (IHC)

Percutaneous liver biopsy specimens collected from the seven patients with hepatic LCH were fixed in 10% neutral buffered formalin before being embedded in paraffin and sectioned at a thickness of 4 µm. The tissue sections were subjected to hematoxylin and eosin (H&E) staining as well as microbiological staining using Ziehl-Neelsen, Gram, periodic acid–Schiff–diastase, and Grocott methenamine silver stains.

For the IHC labeling, the specimen sections were dewaxed, rehydrated, and exposed to a cell-conditioning solution (pH 8.5) at 100°C for antigen retrieval. The sections were subsequently incubated in a solution containing the following primary antibodies: anti-cytokeratin (CK) (polyclonal antiserum), anti-cytokeratin 7 (CK7) (MX053), anti-cluster of differentiation 20 (CD20) (L26), anti-cluster of differentiation 3 (CD3) (MX036), anti-cluster of differentiation 21 (CD21) (EP64), anti-cluster of differentiation 23 (CD23) (MXR015), anti-cluster of differentiation 35 (CD35) (MXR021), anti-smooth muscle actin(SMA) (MX097)and anti-anaplastic lymphoase kinase(ALK) (MX064). Antibodies were purchased from Fuzhou Maixin Biotechnology Development Co., Ltd. (Fuzhou, China) .A multi-tissue “spring roll” positive control block or a relevant positive control was mounted on each slide to ascertain the specificity of each antibody. After sufficient incubation with diluted primary antibodies at the appropriate concentrations, the sections were incubated in secondary antibody solution from a Ventana ultraView Universal DAB Detection Kit for 30 min at 37°C, followed by exposure to 3,3’-diaminobenzidine (DAB) for 8 min for chromogenic detection.

In situ hybridization (ISH)

An ISH assay was performed on the tissue sections using a commercially available Epstein-Barr virus (EBV) oligonucleotide probe complementary to the EBV-encoded small RNA-1 (EBER-1) (PanPath, Amsterdam, Netherlands), according to the manufacturer's instructions. The hybridization signals were visualized using DAB as a chromogen (Vector Laboratories, Inc.), and positive signals were recognized as areas of dark brown nuclear staining under light microscopy. Sections from known EBER-1-positive nasopharyngeal carcinoma(NPC) tissues were used as a positive control, and a sense probe for EBER-1 was used as a negative control.

Clinical Findings

The clinical data of the seven included patients are summarized in Table 1. There were five male and two female patients, two of whom were children and five of whom were adults. The median age was 21 years (range, 3.5–28 years). Three patients presented with diffuse signals (patients 1, 3, and 4), three patients presented with multiple liver masses (patients 5, 6, and 7), and one patient had a solitary liver mass (patient 2). Common presenting symptoms included abdominal pain, fatigue, polydipsia, polyuria, and wasting, although some patients exhibited no symptoms. Biochemical examinations of blood samples collected from the patients revealed that alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) levels were normal or mildly elevated in three cases (patients 1, 2, and 7) and markedly elevated in the other four cases (patients 3, 4, 5, and 6). All patients tested negative for hepatitis viruses A, B, C, D, and E, as well as for the presence of autoimmune antibodies. One patient underwent treatment with microwave ablation and did not experience relapse during the 30 months of follow-up (patient 2). One patient was treated with chemotherapy and underwent liver transplantation but experienced LCH relapse in the donor liver and died 12 months after transplantation (patient 3). The other five patients were treated solely with chemotherapy; of those patients, three remained in good condition and did not experience relapse during the follow-up periods, which lasted from 12–30 months (patients 1, 6, and 7), and two were lost to follow-up (patients 4 and 5).

Table 1

Clinical features of the seven patients with liver LCH
Case	Sex	Clinical manifestation	Changes in biochemical indices based on blood samples	Imaging patterns	Involved site
1	M	Recurrent abdominal pain	AST, ALT, ALP and GGT levels: mild elevation. LDH level: not available	MRI: diffuse signals; multiple plaques detected on the right lobe of the liver; hilar and retroperitoneal lymphadenectasis. MRCP: cholangitis.	Liver
2	M	Asymptomatic	ALT: mild elevation. AST, ALP, GGT, TB, DB and IB: normal. LDH: not available	B-scan ultrasonography: a solid and round hypoechoic nodule in S6/7 segment of liver; size: 14 x 13 mm. MRI: a nodule in S6/7 segment of the liver; size: 19 x 14 mm; consideration of small hepatocellular carcinoma.	Liver
3	M	Jaundice,	AST, ALT and GGT: mild elevation. ALP: raised 3.5 times. TB: raised 3 times. DB: raised 9 times. IB: normal. LDH: not available.	CT: cirrhosis; intrahepatic bile duct dilatation and inflammation; multiple stones.	Liver, skin, and skull
4	M	Abdominal pain, polydipsia, polyuria	ALT: mild elevation. GGT: raised 3.5 times. AST, ALP, TB, DB and IB: normal. LDH: raised 2 times.	B-scan ultrasonography: diffuse changes in the liver; slight enlargement; multiple abnormal echoes in the liver; small bile duct injury. MRI: diffuse liver changes; intrahepatic cholangitis with mild dilatation of intrahepatic and extrahepatic bile ducts; retroperitoneal lymph node enlargement.	Liver and pituitary gland
5	M	Polydipsia, polyuria, wasting	AST and ALT: mild elevation. ALP: raised 2.5 times. GGT: raised 4 times. TB, DB and IB: normal. LDH: not available.	CT, PET-CT, and MRI: diffuse nodular lesions in the liver; inflammatory granulomatous lesions and malignant tumor considered; hilar and peripancreatic lymph node enlargement.	Liver and pituitary gland
6	F	Fatigue, poor appetite, wasting	AST: mild elevation. ALP: raised 5 times. GGT: raised 6 times. LDH: raised 1.5 times. ALT, TB, DB, and IB: normal.	B-scan ultrasonography CT, and MRI: multiple nodules in the liver, with the largest diameter being 12 mm. Hilar lymph node enlargement.	Liver and pituitary gland
7	M	asymptomatic	AST, ALT, ALP, GGT, TB, DB, IB, and LDH: normal	B-scan ultrasonography: multiple hypoechoic areas; inflammation considered. MRI: multiple lesions in the liver. Infectious lesions and cholangiocarcinoma considered.	Liver
Abbreviations: AST, aspartate aminotransferase; ALP, alkaline phosphatase; ALT, alanine transaminase; CT, computed tomography; DB, direct bilirubin; GGT, gamma-glutamyltransferase; F, female; IB, indirect bilirubin; LDH, lactate dehydrogenase; M, male; MRI, magnetic resonance imaging; PET, positron emission tomography; y, years.

Pathologic findings

Three pieces of tissue were collected from each patient via percutaneous liver biopsy; these specimens were grayish-yellow/yellowish-green in color and 1–1.5 cm in length.

Histologically, multifocal lesions were detected in six patients, and solitary lesions were found in only one patient (patient 2). All of the lesions were located in the portal area and exhibited normal or enlarged portal tracts (Fig. 1). LC invasion of the bile duct epithelium was observed in six patients; however, the extent of invasion varied between areas and cases (Fig. 2). In four cases (in patients 1, 5, 6, and 7), the lesions exhibited typical morphological changes (Fig. 3A). In some portals, numerous medium-sized mononuclear cells mixed with a large number of eosinophils were distributed throughout the lesions. These mononuclear cells had oval, grooved, and indented nuclei, with thin nuclear membranes, and an abundance of cytoplasm; however, mitotic figures were rarely observed. The other portals were mildly enlarged, with distributions involving a few eosinophils and one or two LCs invading into the bile duct epithelium (Fig. 2). Hepatic lobular boundary plate inflammation was observed in a few inflammatory cells in the hepatic sinusoids; however, no mononuclear cells were detected in those structures (Fig. 1). In the other three cases (patients 2–4), different morphologies were observed. For example, in Patient 2, numerous small lymphocytes mixed with a small number of eosinophils were distributed throughout the lesion. A few spindle-shaped to ovoid cells with small scattered nucleoli and multinucleated giant cells were occasionally observed, and they were similar in morphology to inflammatory myofibroblastic tumors and inflammatory pseudotumors such as follicular dendritic cell (FDC) tumors (Fig. 3C, D, E). In Patient 3, most portal ducts were enlarged, with fibrosis proliferating around the small bile ducts. Few instances of eosinophil or lymphocyte infiltrations were observed, LCs were absent, and portal ductal proliferation and bile plugs were occasionally observed, all of which was compatible with the diagnosis of sclerosing cholangitis (SC) (Fig. 3B). In patient 4, marked destruction of the large and small bile ducts was observed, with bile spillover. A large number of neutrophils had infiltrated the abscess, and chronic suppurative cholangitis was observed (Fig. 3F), along with evidence of mild LC invasion of the bile duct epithelium in one portal.

Histochemistry, IHC, and ISH

All microbiological staining for bacteria, acid-fast bacilli, and fungi yielded negative results.

The CK and CK7 immunolabeling revealed small bile ducts and delineated bile duct epithelial lesions. The medium-sized mononuclear cells exhibited positive labeling for S100 and CD1a, with negative labeling for CD21, CD23, CD35, smooth muscle actin (SMA), and anaplastic lymphoma kinase (ALK). The lesion in patient 2 harbored large numbers of CD20⁺ B cells and CD3⁺ T cells. The lesions of other patients contained a few CD20⁺ B and CD3⁺ T cells.

The ISH for EBER-1 was negative in all seven patients.

LCH is a rare disease characterized by the clonal proliferation of LCs, which are identical to normal dendritic cells. LCs are atypical and immature cells of the mononuclear phagocytic system that can infiltrate tissue virtually anywhere in the body, and they may manifest in localized lesions or as a component of widespread systemic diseases [7, 9]. The cases described in this report exhibit the typical clinical features of LCH, including the fact that it occurs more commonly in males and in cases of MS-LCH. LCH with hepatic involvement is relatively rare, especially in adults, and usually presents as part of a disseminated disease process [10–12]. Only a few cases of isolated liver involvement have been reported to date [5, 13–15]; for example, Key et al. reported data from nine patients with liver involvement, five of whom solely exhibited hepatic involvement [13]. Most of the studies published to date have been single-case reports. In the present study, patients with LCH with liver involvement were predominantly adults (71.4%), a finding that differs from what has been reported in the literature, and three patients had isolated liver involvement, two of whom were adults and of whom was one a child. This discrepancy could be explained by the fact that our hospital is a general hospital whose Hepatic Department is well-known in South China, and many patients with liver diseases are admitted to our hospital for treatment.

The clinical presentations and imaging signs of LCH involving the liver are variable and nonspecific, and the diagnosis depends on both the site of the lesion and the disease stage. However, some patients were asymptomatic, making a proper diagnosis difficult. Overall, the symptoms of LCH with isolated liver involvement tend to be much milder than those of LCH with the involvement of other organs. In this study, two patients (28.6%) with isolated liver involvement were asymptomatic, while the other five reported upper abdominal discomfort, polydipsia, polyuria, or jaundice. The imaging findings revealed evidence of hepatocellular carcinoma, cholangiocarcinoma, granulomatous inflammation, and cholangitis, among other disease processes, and none of our patients was diagnosed with LCH based on imaging studies alone. Thus, a combination of pathological and immunohistochemical evidence remains the gold standard for the diagnosis of LCH. As reported in the literature, the macroscopic appearance of hepatic lesions in LCH varies from single to multiple in number, from small to large in size, and from subcapsular to deep in terms of the location of nodules. Some authors have reported solid tumor-like or, occasionally, multicystic masses [13, 16, 17]. In the present study, most cases involved multiple lesions, and one case involved the formation of an abscess. Microscopically, LCs selectively affect the portal tract [18]. The LCs had an abundant pink cytoplasm and lobulated, coffee bean-shaped, or contorted nuclei with a fine chromatin pattern and indiscernible nucleoli. In LCH lesions, tumor cells comprise less than 1% to more than 70% of granulomas (median, approximately 8%), and the number of eosinophils and activated T cells varies greatly as well, depending on the status of and factors released as part of the cytokine storm [19–23]. In the present study, four patients had typical morphology in some portals, whereas other portals exhibited mild changes; this morphological variability may depend on the disease stage. For example, the portal region undergoes mild expansion during the early stages of lesion development. In LCH, only individual LCs invade the bile duct epithelium, and only a slight degree of inflammatory cell infiltration of the bile duct occur; thus, it is very difficult to correctly diagnose LCH based on the presence of such morphology from H&E staining, especially in punctured tissue. Under these conditions, observations must be conducted carefully to more accurately assess the presence of bile duct epithelial damage, epithelial vacuolar degeneration, and the spacing beside epithelial cells with any degree of eosinophil infiltration, all of which are clues that could point to the presence of LCH. Labeling of S100 and CD1a using IHC could aid in the detection of LCs and the verification of an LCH diagnosis. LCs are often difficult to identify in the advanced stages of the disease. Portal/periportal fibrosis, bile ductular proliferation, ductopenia, and cirrhosis are the main manifestations of primary sclerosing cholangitis (PSC). In some cases, tumor cells may never be found in liver tissue with nonspecific portal inflammation or SC morphology [13, 16, 17]. This indirect involvement of the liver may occur through the production of a large array of cytokines and chemokines through LCH at other sites [24, 25]. One patient in this study had SC in the absence of LCs, but that individual had a history of skin LCH, which provided insight that led to the diagnosis of liver LCH. After liver transplantation, the host liver was extensively observed, and LCs were found in the focus, confirming direct involvement. Thus, it is important to have a good understanding of a patient’s detailed clinical history in cases of SC in which LCs are undetected based on morphological assessments and IHC. If a patient has extrahepatic LCH or central diabetes insipidus, the lesions may be secondary manifestations of LCH involving the liver.

The disease course of LCH may vary greatly between individual cases. In one patient in this study, a few cells that were spindly to ovoid in shape were observed, which were accompanied by numerous small lymphocytes and a small number of eosinophils; these observations led to the differential diagnosis of inflammatory pseudotumor-like FDC tumors and inflammatory myofibroblastic tumors (IMTs). With respect to FDC tumors, solitary liver lesions are well-circumscribed, with or without a fibrous pseudocapsule, and scattered atypical spindly to ovoid cells with indistinct cell borders, large vesicular nuclei, and distinct nucleoli are invariably present. The atypical cells exhibited positive immunolabeling for FDC markers (CD21⁺ and CD35⁺) and positive EBV detection via ISH, which can facilitate the diagnosis. However, spindle-shaped cells in IMTs were consistently positive for SMA and ALK in 50% of the patients. One patient presented with chronic suppurative cholangitis and abscess formation. In addition, there were a large number of mixed inflammatory cells, including frequently observed eosinophils, in the background in most of the patients. Collectively, all of these factors led to the consideration of possible infections, including those that were bacterial, fungal, and parasitic in nature. However, in the present study, all of the microbial staining techniques failed to identify an infectious cause in any of the patients, and the follow-up information did not suggest the presence of an infection. Importantly, the morphology of LCH involving in the liver is complex, making detection difficult, especially in samples collected via needle biopsy.

Currently, there is no standard treatment for LCH, and progression-free survival among high-risk patients is less than 50% [23]. Liver involvement in cases of is considered a poor prognostic factor, and the treatment for such cases consists of systemic chemotherapy and targeted therapy. SC complicated by the presence of LCH can lead to end-stage liver cirrhosis and poor responses to therapy [11, 16]; in such cases, liver transplantation may be a favorable treatment option [17, 26–29], and the survival rate of children following liver transplantation for LCH-related liver disease is excellent. However, in this study, one patient with SC died of LCH recurrence one year after liver transplantation. The prognosis of patients with LCH with isolated liver involvement is better than that of patients with MS-LCH with liver involvement. Three patients with single-organ involvement, including one patient who underwent ablation and two patients who underwent chemotherapy, experienced favorable outcomes in the present study, which is consistent with the literature. Because early treatment can improve the prognosis of LCH involving the liver, early diagnosis is of primary importance.

In summary, the results of this study confirmed that the morphology of LCH with liver involvement varies greatly between cases and affected areas, making diagnosis difficult, especially based on the findings of needle biopsies. H&E staining and IHC labeling of lesions can provide information that is crucial for ensuring an accurate diagnosis. Bile duct epithelial damage accompanied by eosinophilic infiltration is a clue that can indicate the possibility of LCH; however, as shown in one case in this study, a liver biopsy can reveal the presence of bile duct injury in the absence of LCs, but LCH should still be considered in such cases if the patient has a history of LCH outside the liver or central diabetes insipidus. For a definitive diagnosis, LCH should be differentiated from hepatic parasitic infections, PSC, inflammatory pseudotumor-like FDC tumors, and inflammatory myofibroblastoma.

ALK

anaplastic lymphoma kinase

ALP

alkaline phosphatase

ALT

alanine transaminase

AST

aspartate aminotransferase

cluster of differentiation

computed tomography

DAB

3,3’-diaminobenzidine

direct bilirubin

EBER-1

Epstein-Barr virus-encoded small RNA-1

EBV

Epstein-Barr virus

FDC

follicular dendritic cell

GGT

gamma-glutamyltransferase

H&E

hematoxylin & eosin

indirect bilirubin

IHC

immunohistochemistry

IMT

inflammatory myofibroblastic tumor

ISH

in situ hybridization

LCH

Langerhans cell histiocytosis

MRI

magnetic resonance imaging

MS-LCH

multisystem Langerhans cell histiocytosis

PET

positron emission tomography

PSC

primary sclerosing cholangitis

sclerosing cholangitis

SMA

smooth muscle actin

Ethics approval and consent to participate: This study was approved by the Third Affiliated Hospital of Sun Yat-sen University Review Board.

Consent for publication: Not applicable

Availability of data and materials:Data archiving is not mandated but data will be made available upon reasonable request.

Competing interests:The authors declare that they have no competing interests.

Funding:Application of AI in the Pathological Diagnosis of Hodgkin's Lymphoma (202102010141)

Authors’ Contributions:Qiong Liang, Qian-Qian Chen and Chang Zhao wrote the main manuscript text . Chun-kui Shao, Yi-wang Zhang, Jian-ning Chen and Hai-feng Li prepared figures 1-3. All authors reviewed the manuscript.

Acknowledgements:This study was supported by the Research Fund of Guangzhou Municipal Science and Technology Bureau,China (No. 202102010141).We would like to thank Editage (www.editage.cn) for English language editing.

Garcia Gallo MS, Martinez MP, Abalovich MS et al (2010) Endocrine manifestations of Langerhans cell histiocytosis diagnosed in adults. Pituitary 13(4):298–303
Braier J, Chantada G, Rosso D et al (1999) Langerhans cell histiocytosis: retrospective evaluation of 123 patients at a single institution. Pediatr Hematol Oncol 16(5):377–385
Guyot-Goubin A, Donadieu J, Barkaoui M et al (2008) Descriptive epidemiology of childhood Langerhans cell histiocytosis in France, 2000–2004. Pediatr Blood Cancer 51(1):71–75
Stalemark H, Laurencikas E, Karis J et al (2008) Incidence of Langerhans cell histiocytosis in children: a population-based study. Pediatr Blood Cancer 51(1):76–81
Consing M, Lee HE, Jess H, Vahidi S (2022) Solitary Involvement of the Liver: A Rare Manifestation of Langerhans Cell Histiocytosis. Am J Case Rep 23:e937628
Menon J, Shanmugam N, Valamparampil J et al (2023) Outcomes of liver transplantation in children with Langerhans cell histiocytosis: Experience from a quaternary care center. Pediatr Blood Cancer 70(1):e30024
Leonidas JC, Guelfguat M, Valderrama E (2003) Langerhans' cell histiocytosis. Lancet 361(9365):1293–1295
Ma J, Jiang Y, Chen X, Gong G (2014) Langerhans cell histiocytosis misdiagnosed as liver cancer and pituitary tumor in an adult: A case report and brief review of the literature. Oncol Lett 7(5):1602–1604
Stockschlaeder M, Sucker C (2006) Adult Langerhans cell histiocytosis. Eur J Haematol 76(5):363–368
Pagnoux C, Hayem G, Roux F et al (2003) [Sclerosing cholangitis as a complication of Langerhans'cell histiocytosis]. Rev Med Interne 24(5):324–327
Nagai S, Kusumoto M, Yakushiji S et al (2004) [A case of pulmonary Langerhans' cell histiocytosis with liver involvement]. Nihon Kokyuki Gakkai Zasshi 42(10):924–927
Sampathkumar S, Younger C, Cramer H et al (2002) Langerhans' cell histiocytosis involving the pituitary, thyroid, lung, and liver. Endocr Pract 8(3):217–221
Kaplan KJ, Goodman ZD, Ishak KG (1999) Liver involvement in Langerhans' cell histiocytosis: a study of nine cases. Mod Pathol 12(4):370–378
Buza N, Lagarde DC, Dash S, Haque S (2004) Langerhans cell histiocytosis: report of a single organ involvement in a child. J Cell Mol Med 8(3):397–401
Ji H, Wu J, Yang G et al (2017) Fluorrine-18-fluorodeoxyglucose positron emission tomography/computed tomography of adult liver Langerhans cell histiocytosis. Hell J Nucl Med 20(1):97–99
Levy S, Capron D, Joly JP et al (1998) Hepatic nodules as single organ involvement in an adult with Langerhans cell granulomatosis. A case report. J Clin Gastroenterol 26(1):69–73
Braier J, Ciocca M, Latella A et al (2002) Cholestasis, sclerosing cholangitis, and liver transplantation in Langerhans cell Histiocytosis. Med Pediatr Oncol 38(3):178–182
Jaffe R (2004) Liver involvement in the histiocytic disorders of childhood. Pediatr Dev Pathol 7(3):214–225
Berres ML, Lim KP, Peters T et al (2014) BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups. J Exp Med 211(4):669–683
Senechal B, Elain G, Jeziorski E et al (2007) Expansion of regulatory T cells in patients with Langerhans cell histiocytosis. PLoS Med 4(8):e253
Laman JD, Leenen PJ, Annels NE et al (2003) Langerhans-cell histiocytosis 'insight into DC biology'. Trends Immunol 24(4):190–196
Allen CE, Li L, Peters TL et al (2010) Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells. J Immunol 184(8):4557–4567
Allen CE, Merad M, McClain KL (2018) Langerhans-Cell Histiocytosis. N Engl J Med 379(9):856–868
Egeler RM, Annels NE, Hogendoorn PC (2004) Langerhans cell histiocytosis: a pathologic combination of oncogenesis and immune dysregulation. Pediatr Blood Cancer 42(5):401–403
Gey T, Bergoin C, Just N et al (2004) [Langerhans cell histiocytosis and sclerosing cholangitis in adults]. Rev Mal Respir 21(5 Pt 1):997–1000
Griffiths W, Davies S, Gibbs P et al (2006) Liver transplantation in an adult with sclerosing cholangitis due to Langerhans cell histiocytosis. J Hepatol 44(4):829–831
Ziogas IA, Kakos CD, Wu WK et al (2021) Liver Transplantation for Langerhans Cell Histiocytosis: A US Population-Based Analysis and Systematic Review of the Literature. Liver Transpl 27(8):1181–1190
Wang Q, Jin S, Xiang B, Chen J (2022) Liver transplantation in a child with liver cirrhosis caused by langerhans cell histiocytosis: a case report. BMC Pediatr 22(1):18
Abdallah M, Genereau T, Donadieu J et al (2011) Langerhans' cell histiocytosis of the liver in adults. Clin Res Hepatol Gastroenterol 35(6–7):475–481

No competing interests reported.

Download PDF

Reviewers agreed at journal
13 Nov, 2024
Reviewers agreed at journal
12 Nov, 2024
Reviewers agreed at journal
10 Nov, 2024
Reviewers agreed at journal
09 Nov, 2024
Reviewers agreed at journal
07 Nov, 2024
Reviewers invited by journal
07 Nov, 2024
Editor assigned by journal
23 Oct, 2024
Submission checks completed at journal
23 Oct, 2024
First submitted to journal
23 Oct, 2024

You are reading this latest preprint version

Diagnosis of Langerhans cell histiocytosis via percutaneous liver biopsy

Status:

Version 1

Abstract

Figures

BACKGROUND

METHODS

Patient selection and ethical approval

Histology and immunohistochemistry (IHC)

In situ hybridization (ISH)

RESULTS

Clinical Findings

Pathologic findings

Histochemistry, IHC, and ISH

DISCUSSION

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1