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Cervical Langerhans cell histiocytosis (histiocytosis X) A 17-year-old man presented to the emergency department with persistent left neck lymphadenopathy. Apart from dull neck pain, there was no associated fever, rigors, dysphagia, dysphonia, unintentional loss of weight or facial weakness. The patient was a nonsmoker and was otherwise well with no significant medical history. Upon examination, there was a non-tender, mobile left-sided 2 × 2 cm level III cervical lymph node. The rest of the ENT and head and neck examination was otherwise unremarkable. A positron emission tomography (PET) scan performed revealed increased tracer uptake in the cervical lymph node region (Fig. 1). Fine-needle aspiration cytology was inconclusive. The patient subsequently underwent open biopsy of the neck mass, with the histology confirming the diagnosis of Langerhans cell histiocytosis (LCH) (histiocytosis X) (Figs 2,3). LCH is a rare disorder and the true incidence is unknown. The incidence appears to range from one to two cases per million in adults and three to five cases per million in children.1,2 Histiocytosis is a group of disorders characterized by proliferation of mononuclear phagocytic (macrophages) cells and is generally divided into Langerhans and non-Langerhans types. The classification of LCH is given when the morphology and immunophenotype of the histiocytes resemble Langerhans cells (specialized dendritic cells usually found in the mucosa and skin). The pathophysiology of LCH is unclear, and the main postulated mechanisms include either a neoplastic process or a reactive process, and further studies are currently underway.3,4 LCH can affect a variety of organs and is commonly divided into three main groups – solitary or unifocal lesion being the most
common, multifocal unisystem disease and multisystem disease.4 In unifocal disease, bone involvement is present in more than 90% of cases.5 Extra-skeletal involvement may involve a variety of organs, including the skin, lymph nodes, lung, liver, spleen, bone marrow or
Fig. 2. Pathological analysis of the sectioned lymph node showed mild to moderate expansion of medullary sinuses by a population of atypical (neoplastic) cells (40× magnification).
Fig. 1. Positron emission tomography showed uptake of tracer in the cervical lymph node region, correlating clinically with the palpable neck mass. Minimal avidity in the left axillary and right inguinal regions was likely physiological and deemed insignificant.
© 2014 Royal Australasian College of Surgeons
ANZ J Surg •• (2014) ••–••
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Fig. 3. The characteristic appearance of Langerhans cells with a typical background of population of eosinophils was observed. The Langerhans cells were of medium size and showed irregular nuclear outlines with grooving and indentations. The cells had vesicular chromatin and variably prominent chromo-centres and had a small amount of amphophilic cytoplasm. Of note, there were no Reed–Sternberg forms seen. The Langerhans cells showed immunohistochemical positivity for CD1a (stained brown) (200× magnification).
central nervous system, leading to a variety of possible presentations.3,5 Isolated lymph node involvement is however considered rare.6 The diagnosis of LCH is based upon histological or cytological analysis of a tissue specimen, in conjunction with the clinical history and findings. The presence of pathologic Langerhans cells seen on microscopy is confirmed with immunochemical staining. This may include staining to demonstrate positivity with S100, CD1A and Langerin (CD207).5,7 If electron microscopy is performed, this typically shows Birbeck granules.8 Management of LCH is based upon a number of factors, including disease location, the number of lesions, the number of organs or systems involved, and whether risk organs are involved. Risk organs include the spleen, liver or haematopoietic system.9 Based upon the above-mentioned factors, treatment options may include local resection, bone curettage, topical therapy or systemic chemotherapy, for instance, with a combination of vinblastine and prednisolone.9,10 In our patient, following the excision biopsy of the lymph nodes, there was fortunately spontaneous regression of the cervical neck mass and a corresponding decrease in uptake on repeat positron emission tomography scanning. Following a multidisciplinary team meeting, it was deemed appropriate that a watchful waiting approach be adopted given that there was only single organ involvement. The diagnosis of LCH can be challenging given its rare occurrence. Our case demonstrates the need to consider all potential diagnoses in a patient presenting with isolated lymph node enlargement.
References 1. Baumgartner I, von Hochstetter A, Baumert B, Luetolf U, Follath F. Langerhans’-cell histiocytosis in adults. Med. Pediatr. Oncol. 1997; 28: 9–14. 2. Carstensen H, Ornvold K. The epidemiology of Langerhans cell histiocytosis in children in Denmark, 1975–89. Med. Pediatr. Oncol. 1993; 21: 387–8.
3. Weitzman S, Egeler RM. Langerhans cell histiocytosis: update for the pediatrician. Curr. Opin. Pediatr. 2008; 20: 23–9. 4. Kumar N, Sayed S, Vinayak S. Diagnosis of Langerhans cell histiocytosis on fine needle aspiration cytology: a case report and review of the cytology literature. Patholog. Res. Int. 2011; 2011: 439518. 5. Lieberman PH, Jones CR, Steinman RM et al. Langerhans cell (eosinophilic) granulomatosis: a clinicopathologic study encompassing 50 years. Am. J. Surg. Pathol. 1996; 20: 519–52. 6. Williams JW, Dorfman RF. Lymphadenopathy as the initial manifestation of histiocytosis X. Am. J. Surg. Pathol. 1979; 3: 405–21. 7. Lau SK, Chu PG, Weiss LM. Immunohistochemical expression of Langerin in Langerhans cell histiocytosis and non-Langerhans cell histiocytic disorders. Am. J. Surg. Pathol. 2008; 32: 615–9. 8. Dziegiel P, Dolinska-Krajewska B, Dumanska M et al. Coexpression of CD1a, Langerin and Birbeck’s granules in Langerhans cell histiocytoses (LCH) in children: ultrastructural and immunocytochemical studies. Folia Histochem. Cytobiol. 2007; 45: 21–5. 9. Minkov M. Multisystem Langerhans cell histiocytosis in children: current treatment and future directions. Paediatr. Drugs 2011; 13: 75–86. 10. Al-Muazen Y, El-Shawarby M, Al-Sowayan S. Orbital unifocal Langerhans cell histiocytosis (eosinophilic granuloma). Pan Arab J. Neurosurg. 2009; 13: 66–9.
Hau Choong Aw,* MBBS (Hons) Christopher F. D. Li Wai Suen,* MBBS (Hons) Anthony Longano,† MBBS (Hons), FRCPA Vibhuti Mahanta,* FRACS, MS ENT, DOHNS, MRCS Neil Vallance,* MBBS, FRACS Departments of *Ear, Nose & Throat/Head & Neck Surgery and †Anatomical Pathology, Monash Medical Centre, Melbourne, Victoria, Australia doi: 10.1111/ans.12794
© 2014 Royal Australasian College of Surgeons
Cervical Langerhans cell histiocytosis (histiocytosis X) A 17-year-old man presented to the emergency department with persistent left neck lymphadenopathy. Apart from dull neck pain, there was no associated fever, rigors, dysphagia, dysphonia, unintentional loss of weight or facial weakness. The patient was a nonsmoker and was otherwise well with no significant medical history. Upon examination, there was a non-tender, mobile left-sided 2 × 2 cm level III cervical lymph node. The rest of the ENT and head and neck examination was otherwise unremarkable. A positron emission tomography (PET) scan performed revealed increased tracer uptake in the cervical lymph node region (Fig. 1). Fine-needle aspiration cytology was inconclusive. The patient subsequently underwent open biopsy of the neck mass, with the histology confirming the diagnosis of Langerhans cell histiocytosis (LCH) (histiocytosis X) (Figs 2,3). LCH is a rare disorder and the true incidence is unknown. The incidence appears to range from one to two cases per million in adults and three to five cases per million in children.1,2 Histiocytosis is a group of disorders characterized by proliferation of mononuclear phagocytic (macrophages) cells and is generally divided into Langerhans and non-Langerhans types. The classification of LCH is given when the morphology and immunophenotype of the histiocytes resemble Langerhans cells (specialized dendritic cells usually found in the mucosa and skin). The pathophysiology of LCH is unclear, and the main postulated mechanisms include either a neoplastic process or a reactive process, and further studies are currently underway.3,4 LCH can affect a variety of organs and is commonly divided into three main groups – solitary or unifocal lesion being the most
common, multifocal unisystem disease and multisystem disease.4 In unifocal disease, bone involvement is present in more than 90% of cases.5 Extra-skeletal involvement may involve a variety of organs, including the skin, lymph nodes, lung, liver, spleen, bone marrow or
Fig. 2. Pathological analysis of the sectioned lymph node showed mild to moderate expansion of medullary sinuses by a population of atypical (neoplastic) cells (40× magnification).
Fig. 1. Positron emission tomography showed uptake of tracer in the cervical lymph node region, correlating clinically with the palpable neck mass. Minimal avidity in the left axillary and right inguinal regions was likely physiological and deemed insignificant.
© 2014 Royal Australasian College of Surgeons
ANZ J Surg •• (2014) ••–••
2
Images for surgeons
Fig. 3. The characteristic appearance of Langerhans cells with a typical background of population of eosinophils was observed. The Langerhans cells were of medium size and showed irregular nuclear outlines with grooving and indentations. The cells had vesicular chromatin and variably prominent chromo-centres and had a small amount of amphophilic cytoplasm. Of note, there were no Reed–Sternberg forms seen. The Langerhans cells showed immunohistochemical positivity for CD1a (stained brown) (200× magnification).
central nervous system, leading to a variety of possible presentations.3,5 Isolated lymph node involvement is however considered rare.6 The diagnosis of LCH is based upon histological or cytological analysis of a tissue specimen, in conjunction with the clinical history and findings. The presence of pathologic Langerhans cells seen on microscopy is confirmed with immunochemical staining. This may include staining to demonstrate positivity with S100, CD1A and Langerin (CD207).5,7 If electron microscopy is performed, this typically shows Birbeck granules.8 Management of LCH is based upon a number of factors, including disease location, the number of lesions, the number of organs or systems involved, and whether risk organs are involved. Risk organs include the spleen, liver or haematopoietic system.9 Based upon the above-mentioned factors, treatment options may include local resection, bone curettage, topical therapy or systemic chemotherapy, for instance, with a combination of vinblastine and prednisolone.9,10 In our patient, following the excision biopsy of the lymph nodes, there was fortunately spontaneous regression of the cervical neck mass and a corresponding decrease in uptake on repeat positron emission tomography scanning. Following a multidisciplinary team meeting, it was deemed appropriate that a watchful waiting approach be adopted given that there was only single organ involvement. The diagnosis of LCH can be challenging given its rare occurrence. Our case demonstrates the need to consider all potential diagnoses in a patient presenting with isolated lymph node enlargement.
References 1. Baumgartner I, von Hochstetter A, Baumert B, Luetolf U, Follath F. Langerhans’-cell histiocytosis in adults. Med. Pediatr. Oncol. 1997; 28: 9–14. 2. Carstensen H, Ornvold K. The epidemiology of Langerhans cell histiocytosis in children in Denmark, 1975–89. Med. Pediatr. Oncol. 1993; 21: 387–8.
3. Weitzman S, Egeler RM. Langerhans cell histiocytosis: update for the pediatrician. Curr. Opin. Pediatr. 2008; 20: 23–9. 4. Kumar N, Sayed S, Vinayak S. Diagnosis of Langerhans cell histiocytosis on fine needle aspiration cytology: a case report and review of the cytology literature. Patholog. Res. Int. 2011; 2011: 439518. 5. Lieberman PH, Jones CR, Steinman RM et al. Langerhans cell (eosinophilic) granulomatosis: a clinicopathologic study encompassing 50 years. Am. J. Surg. Pathol. 1996; 20: 519–52. 6. Williams JW, Dorfman RF. Lymphadenopathy as the initial manifestation of histiocytosis X. Am. J. Surg. Pathol. 1979; 3: 405–21. 7. Lau SK, Chu PG, Weiss LM. Immunohistochemical expression of Langerin in Langerhans cell histiocytosis and non-Langerhans cell histiocytic disorders. Am. J. Surg. Pathol. 2008; 32: 615–9. 8. Dziegiel P, Dolinska-Krajewska B, Dumanska M et al. Coexpression of CD1a, Langerin and Birbeck’s granules in Langerhans cell histiocytoses (LCH) in children: ultrastructural and immunocytochemical studies. Folia Histochem. Cytobiol. 2007; 45: 21–5. 9. Minkov M. Multisystem Langerhans cell histiocytosis in children: current treatment and future directions. Paediatr. Drugs 2011; 13: 75–86. 10. Al-Muazen Y, El-Shawarby M, Al-Sowayan S. Orbital unifocal Langerhans cell histiocytosis (eosinophilic granuloma). Pan Arab J. Neurosurg. 2009; 13: 66–9.
Hau Choong Aw,* MBBS (Hons) Christopher F. D. Li Wai Suen,* MBBS (Hons) Anthony Longano,† MBBS (Hons), FRCPA Vibhuti Mahanta,* FRACS, MS ENT, DOHNS, MRCS Neil Vallance,* MBBS, FRACS Departments of *Ear, Nose & Throat/Head & Neck Surgery and †Anatomical Pathology, Monash Medical Centre, Melbourne, Victoria, Australia doi: 10.1111/ans.12794
© 2014 Royal Australasian College of Surgeons
