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  Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 59  |  Issue : 1  |  Page : 123-127
 

Unusual presentation of Langerhans cell sarcoma as bilateral submandibular gland swelling – A rare case report


Department of Pathology, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha, India

Date of Submission23-Jul-2020
Date of Decision23-Jul-2020
Date of Acceptance21-Jan-2021
Date of Web Publication19-May-2022

Correspondence Address:
Nibedita Sahoo
Department of Pathology, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_819_20

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 » Abstract 


Langerhans cell sarcoma (LCS) is a rare malignant tumor of Langerhans cells and uncommonly involves head and neck regions. Unlike Langerhans cell histiocytosis (LCH), it has an aggressive clinical course with malignant cytological features. Till now, a handful of cases have been reported and the common anatomical sites involved are skin, lymph node, and bone in loco – regional cases and lymph node, lung, liver, spleen, and bone in disseminated disease. Due to its rarity, standard protocols of treatment for these patients are not yet well established. Herein, we report such a case in a 25-year-old male presenting with a bilateral submandibular swelling, which was diagnosed as LCH on Fine Needle Aspiration Cytology (FNAC) and later confirmed to be a case of LCS in histopathological examination and immunohistochemistry. The authors are aware of only a single similar case being reported in the English literature.


Keywords: Histiocytosis, Langerhans cell, sarcoma, submandibular gland


How to cite this article:
Mohanty P, Sahoo N, Lenka A, Bhattacharyya S. Unusual presentation of Langerhans cell sarcoma as bilateral submandibular gland swelling – A rare case report. Indian J Cancer 2022;59:123-7

How to cite this URL:
Mohanty P, Sahoo N, Lenka A, Bhattacharyya S. Unusual presentation of Langerhans cell sarcoma as bilateral submandibular gland swelling – A rare case report. Indian J Cancer [serial online] 2022 [cited 2022 Jul 7];59:123-7. Available from: https://www.indianjcancer.com/text.asp?2022/59/1/123/345487





 » Introduction Top


Langerhans cell histiocytosis (LCH) and sarcoma (LCS) are neoplasms derived from proliferation of Langerhan-type cells that share immunophenotypic and ultrastructural similarities with antigen-presenting Langerhans cells (LCs) of mucosal sites and skin.[1] Recent studies suggest that LCH arises from bone marrow-derived immature myeloid dendritic cells rather than from epidermal LCs and is classified under histiocytic and dendritic cell neoplasms in the WHO classification.[2] Though both LCH and LCS arise from the clonal proliferation of LCs, the latter differs from the former in their atypical cytomorphological features and aggressive clinical course.[1] The incidence of LCH is 4.0–5.4 per million of population, whereas it is unknown for LCS and till now only a handful of cases have been reported.[3] These neoplasms can be localized to a single system or disseminated, involving multiple systems. For LCH, bone is the most common site of unisystem disease, followed by skin, lymph node, and lungs, while multisystem disease commonly affects skin, bone, liver, spleen, and bone marrow. Common anatomical sites involved in LCS are skin, lymph node, and bone in loco regional cases and lymph node, lung, liver, spleen, and bone in disseminated disease.[1],[3] Salivary gland involvement by LC neoplasm is extremely rare and after a detailed search of English literature, we found only 14 cases [Table 1], of which parotid gland involvement is relatively common.[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] LCS involving submandibular gland is still rarer, and to the best of authors knowledge, our case is the second case adding to the English literature.
Table 1: The details of the reported cases of salivary gland involvement Langerhans cell neoplasms

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 » Case Summary Top


A 25-year-old male presented with bilateral painless submandibular gland swelling for 6 months, and the left-side swelling was rapidly increasing over 17 days. Examination revealed that left-side swelling being larger than the right side and was firm in consistency [Figure 1]a. He was a nonsmoker with no history of diabetes mellitus, hypertension, cough, or any kind of skin disease. On enquiry, he revealed history of polydipsia and polyuria for the last 1 year. General examination showed no hepatosplenomegaly or lymphadenopathy, and his routine hematological workup was within the normal limit. Biochemical & hormonal assay confirmed the presence of central diabetes insipidus. Ultrasonogram revealed bilateral submandibular well-defined, lobulated, heteroechoic mass with internal vascularity. CECT contrast -enhanced computed of neck showed bilateral submandibular gland enlargement (left > right) with diffuse heterogeneously enhancing infiltrative parenchymal lesion and increased intralesional vascularity [Figure 1]b. The glands were of size 53 × 43 mm and 43 × 23 mm on left and right side, respectively. Multiple bilateral homogenously enhancing subcentimeteric level IB & V lymph nodes were present. Possibilities of lymphomatous infiltration or histiocytosis were suggested.
Figure 1: (a) Bilateral submandibular swellings, more marked on left side (arrow). (b) CECT image showing bilateral heterogeneously enhancing submandibular gland (arrows) with increased vascularity. (c) Aspiration cytology showing histiocyte-like cells with moderate pale cytoplasm, round to oval nucleus, admixed lymphocytes, and eosinophils. Mitotic figures highlighted by arrow. [Diff Quick 400X] Grooves appreciated in wet fixed smears (Inset)[H&E 400X]

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FNAC from bilateral sub-mandibular gland swellings revealed,cellular smears comprising of polymorphous population of histiocyte-like cells, lymphocytes, and eosinophils. The histiocytic cells had vesicular chromatin with grooved nuclei and abundant pale eosinophilic cytoplasm. Good numbers of mitotic figures were also noted [Figure 1]c. With these findings, a diagnosis of LCH involving bilateral submandibular glands was rendered. Incisional biopsy of the left-side submandibular gland was done for confirmation of the cytological diagnosis.

Histopathology revealed salivary gland parenchyma infiltrated by dense inflammatory cells, forming eosinophilic microabscess, lymphoid aggregates, and admixed pale looking cells with round to oval nuclei, vesicular chromatin, moderately weak eosinophilic cytoplasm with some of them having nuclear grooving [Figure 2]a. Histiocytic cells were also seen infiltrating and destroying the ducts (inset). Hypercellular foci were noted composed of predominant population of histiocytic cells arranged in sheets with features of nuclear atypia-like anisonucleosis, irregular nuclear outline, and some with prominent nucleoli. Some cells with absence of nuclear grooves and some with multiple nuclear grooves including multinucleated forms were also observed [Figure 2]b, [Figure 2]c, [Figure 2]d. The mitotic activity was brisk (35–40/10 high-power field) along with atypical forms [Figure 2]b and [Figure 2]c. On immunohistochemical study, tumor cells were reactive for S100 [Figure 2]f, CD1a [Figure 2g], and CD68 with a proliferative index (Ki-67) of 60%–70% [Figure 2e]. With these findings, a final histopathological diagnosis of LCS was rendered.
Figure 2: (a) Salivary gland tissue infiltrated by pale looking cells and admixed eosinophils forming microabscess (arrow)[H&E 40X] Inset highlighting infiltration and destruction of ducts [H&E, 100X]. (b and c) Hypercellular area with anisokaryosis and brisk mitosis (Arrow)[H& E, 400X]. (d) Admixed atypical multinucleated cells (thick arrow) and few cells with multiple grooves giving lobulated appearance (thin arrow)[H& E, 400X]. (e-g) Ki 67 immunostain (e) (100X) Positive immunostain for S100 (f) and CD1a (g) (diaminobenzidine, 400X)

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His positron emission tomography/computed tomography (PET/CT) revealed that the disease activity was limited to the submandibular glands only. Dynamic contrast-enhanced pituitary MRI revealed pituitary stalk thickening with the absence of posterior pituitary bright spot.

The patient received a single cycle of systemic chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen and desmopressin supplementation. However, the patient was lost to follow-up.


 » Discussion Top


LCS is an extremely rare malignant tumor of LCs with propensity of rapid growth, local invasion, recurrence, and metastasis. Albeit broad age range is affected, it is primarily a disease of adult population with a median age of 41 years.[1] Characteristic morphology of LCs, i.e., longitudinal grooved nuclei, presence of Birbeck granules on electron microscopy, and immunohistochemical expression of CD1a, S-100, Langerin (CD207) with variable positivity for CD68 are present in LCS along with atypical cytomorphology and high mitosis.[3] Somatic mutations activating the mitogen-activated protein kinase signaling pathway are commonly observed in LCH, with B-Raf V600E mutation identified in over half of the cases.[18],[19] Frequent homozygous loss of cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) locus (9p21) and both mitogen-activated protein 2 kinase 1 (MAP2K1) and neuroblastoma -RAS viral oncogene homolog (NRAS) genes mutations are observed in LCS.[20],[21] Several etiological factors proposed for the development of LCS are immunosuppression (posttransplant patients), viruses, and prior hematological diseases. Murakami et al. examined seven LCS tissue samples demonstrating the presence of Merkel cell polyomavirus (MCPmV) DNA in all seven cases of LCS and at significantly higher levels of amplification than in MCPmV positive LCH cases (P < 0.01).[22] Development of LCS is usually thought to be de novo or occasionally from preexisting LCH[23],[24]; in our case, probably sudden increase in size and histopathology displaying focal LCH like area favored an origin from preexisting LCH. In the present case, features of central diabetes insipidus and MRI findings suggested the possibility of involvement of the hypothalamic–pituitary axis and a multisystem disease.

Considering its rareness in the salivary gland and poorly differentiated morphology, LCS should be differentially diagnosed from other malignancies like anaplastic large cell lymphoma, myeloid sarcoma, and amelanotic melanoma. Morphological features like the presence of nuclear grooves, admixed eosinophils and immunohistochemical expression of CD1a, S 100 protein, and Langerin establishes the final diagnosis.

There is no general consensus on the treatment of LCS and the management varies from chemotherapy to surgery, radiation, or a combination of them. A literature review of LCS found an overall poor survival, 58% at 1 year, and outcomes were poorer in disseminated presentations.[3] It has been observed that more localized disease confers a survival advantage with complete surgical excision and margin clearance. Limited data suggests adjuvant chemotherapy and radiation for local or locoregional LCS with adverse features after surgery, such as positive margins, immunosuppression, other hematological disease, and clinical concerns. Advance LCS with multiple organ involvement adjuvant systemic combination chemotherapy such as CHOP or CHOP-like regimen may be helpful.[24]

LCS is an extremely rare and poorly recognized tumor in the salivary gland with a debatable pathophysiology, clinical course, imaging findings, and treatment protocols. Thorough sampling and detailed microscopic examination including immunohistochemistry (IHC) of the resected tumor tissue is essential to establish the pathological diagnosis. Further larger studies should be done to unfold the biological behaviour of this entity, which may provide a future basis for potential targeted therapy.

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 initial s 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.



 
 » References Top

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Weiss LM, Jaffe R, Facchetti F. Tumours derived from Langerhans cells. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al.(Eds):. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues(Revised 4th ed. IARC; Lyon 2017:470-73.  Back to cited text no. 1
    
2.
Allen CE, Li L, Peters TL, Leung HE, Yu A, Man T, et al. Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells. J Immunol 2010;184:4557-67.  Back to cited text no. 2
    
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Howard JE, Dwivedi RC, Masterson L, Jani P. Langerhans cell sarcoma: A systematic review. Cancer Treat Rev 2015;41:320-31.  Back to cited text no. 3
    
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Green I, Behar AJ, Shanon E, Gorsky M. Multifocal extraosseous eosinophilic granuloma of the head and neck. Arch Otolaryngol Head Neck Surg 1988;114:561-3.  Back to cited text no. 4
    
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Weinmann P, Crestani B, Tazi A, Genereau T, Mal H, Aubier M, et al. 111In-pentetreotide scintigraphy in patients with Langerhans' cell histiocytosis. J Nucl Med 2000;41:1808-12.  Back to cited text no. 5
    
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Shima H, Inokuchi M, Shimada H. A case of multisystem Langerhans cell histiocytosis with primary hypothyroidism followed by type 1 diabetes mellitus. Pediatr Blood Cancer 2009;53:232-4.  Back to cited text no. 10
    
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Yuan X, Tang M, Sheng Q, Zhu X, Zhang Q. Swelling of bilateral parotid glands: An unusual symptom of multisystem Langerhans cell histiocytosis. SAGE Open Med Case Rep 2014;2: 2050313X1453122.  Back to cited text no. 13
    
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Yang S, Chen X, Zhang J, Fang Q. Isolated Langerhans cell histiocytosis of the sublingual gland in an adult. Int J Clin Exp Pathol 2015;8:13647-5.  Back to cited text no. 14
    
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Lee G, Song K, Park KW, Koo BS. A case of langerhans cell sarcoma presenting as submandibular gland mass. Korean J Otorhinolaryngol-Head Neck Surg 2019;62:520-3.  Back to cited text no. 15
    
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Ito H, Ito M, Kakuta Y, Takeshi K, Koji O, Ogura T. Multisystem Langerhans cell histiocytosis in an adult non-smoker treated with steroid therapy. Respirol Case Rep 2020;8:e00603.  Back to cited text no. 16
    
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Wang BB, Ye JR, Li YL, Jin Y, Chen ZW, Li JM, et al. Multisystem involvement Langerhans cell histiocytosis in an adult: A case report. World J Clin Cases 2020;8:4966-74.  Back to cited text no. 17
    
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Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood 2010;116:1919-23.  Back to cited text no. 18
    
19.
Sahm F, Capper D, Preusser M, Meyer J, Stenzinger A, Lasitschka F, et al. BRAFV600E mutant protein is expressed in cells of variable maturation in Langerhans cell histiocytosis. Blood 2012;120:e28-34.  Back to cited text no. 19
    
20.
Xerri L, Adélaïde J, Popovici C, Garnier S, Guille A, Mescam-Mancini L, et al. CDKN2A/B deletion and double-hit mutations of the MAPK pathway underlie the aggressive behavior of Langerhans cell tumors. Am J Surg Pathol 2018;42:150-9.  Back to cited text no. 20
    
21.
Aguirre LE, Schwartz I, Chapman J, Larsen MF, Alencar A. Adult Langerhans cell histiocytosis presenting with multisystem involvement and sarcomatoid features: A case report. J Med Case Rep 2020;14:169.  Back to cited text no. 21
    
22.
Kurakami I, Matsushita M, Iwasaki T. High viral loads of Merkel cell polyomavirus DNA sequences in Langerhans cell sarcoma tissues. Infect Agents Cancer 2014;9:15.  Back to cited text no. 22
    
23.
Lee JS, Ko GH, Kim HC, Jang IS, Jeon KN, Lee JH. Langerhans cell sarcoma arising from Langerhans cell histiocytosis: A case report. J Korean Med Sci 2006;21:577-80.  Back to cited text no. 23
    
24.
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