Abstract
This is an unusual adult case of a metastatic well‐differentiated neuroendocrine tumor with incidentally discovered subtle involvement of Langerhans cell histiocytosis (LCH), a clonal proliferation of Langerhans cells. It is important to recognize that LCH can often co‐exist with other malignancies (solid > hematologic).
Keywords: BRAF mutation, langerhans cell histiocytosis (LCH), liver, MAP2K1 mutation, neuroendocrine tumor (NET)
We describe an unusual adult case of a metastatic WD‐NET with incidental LCH. It is important to recognize that adult LCH can often co‐exist with other malignancies, as it may otherwise be histopathologically missed.
A 38‐year‐old man with pancreatic well‐differentiated neuroendocrine tumor (WD‐NET) underwent resection and chemotherapy. Two months later, CT showed multiple liver lesions but no lesions in any other site. A liver biopsy demonstrated metastatic WD‐NET with an intimately admixed proliferation of smaller cells containing scant cytoplasm and elongated nuclei with nuclear grooves (Figure 1A–E). Unlike the WD‐NET, the small cells were negative for synaptophysin and chromogranin and positive for CD1a, langerin, and S100, confirming the diagnosis of Langerhans cell histiocytosis (LCH) (Figure 1D–H). Capture‐based DNA sequencing of the liver biopsy revealed a BRAF p.V600E mutation and a TSC2 p.E159* mutation, both at subclonal mutant allele frequencies. BRAF V600E immunohistochemistry was positive only in the LCH (Figure 1I), consistent with the subclonal allele frequency. Furthermore, LCH are known to harbor frequent mutations in BRAF p.V600E or MAP2K1, but not in TSC2. 1 , 2 , 3 Pancreatic WD‐NET, on the contrary, demonstrate frequent mutations in MEN1, DAXX, ATRX, and TSC2, but not in BRAF. 4 , 5 , 6
FIGURE 1.
Panel (A) (H&E, 200x) and Panel (B) (H&E, 400x) In this liver biopsy, there is a hepatoid metastatic well‐differentiated neuroendocrine tumor (WD‐NET) with large ovoid nuclei, fine chromatin, and eosinophilic cytoplasm with admixed smaller Langerhans cells. Panel (C) A higher magnification (H&E, 1000x) shows the atypical Langerhans cells (left) with smaller nuclei (relative to the neuroendocrine tumor in the lower right corner of the image) and irregular/elongated nuclear contours, indistinct nucleoli, and eosinophilic cytoplasm. Some of the nuclei have grooves/folds typical of Langerhans cells. Scattered eosinophils are also easily identified in the background. Panel (D) The WD‐NET component is diffusely positive for synaptophysin immunostain (200x). Panel (E) The WD‐NET component is diffusely positive for chromogranin A immunostain (200x). Panel (F) The Langerhans cell histiocytosis (LCH) component is positive for CD1a immunostain (400x). Panel (G) The LCH component is positive for langerin immunostain (400x). Panel (H) The LCH component is positive for S100 immunostain (400x). Panel (I) The LCH component (left) shows positive immunoreactivity for BRAF V600E stain, whereas the WD‐NET component (bottom right) is negative for BRAF V600E (1000x)
This is an unusual case of metastatic WD‐NET with co‐existing LCH, highlighting that adult LCH often co‐occurs with other malignancies. 1 , 2 , 3 The patient received peptide receptor radionuclide therapy for WD‐NET (LCH not treated) and has been alive >1 year post‐biopsy.
AUTHOR CONTRIBUTIONS
NMJ and KWW were involved in conceptualization of study as well as manuscript preparation, editing, and proofreading of the final manuscript.
FUNDING INFORMATION
No funding was provided for this article.
CONFLICT OF INTEREST STATEMENT
We declare no competing interests.
ETHICAL APPROVAL
The study was approved by the Institutional Review Board for human subjects research at UCSF Medical Center (IRB # 18–25,787).
CONSENT
Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.
ACKNOWLEDGMENT
None.
Joseph NM, Wen KW. Incidental Langerhans cell histiocytosis associated with metastatic neuroendocrine tumor in the adult liver. Clin Case Rep. 2023;11:e6922. doi: 10.1002/ccr3.6922
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.