Langerhans cell histiocytosis of the thyroid gland. A case report

BACKGROUND: The variant of Langerhans histiocytosis commonly encountered in adults is the benign, localized form (eosinophilic granuloma). The more-aggressive or diffuse type (Letterer-Siwe disease) is rare in adults. CASE: A 28-year-old woman presented with enlargement of the thyroid gland three years after she had been diagnosed with and placed on treatment for diabetes insipidus. Thyroidectomy was performed following an initial fine needle aspiration cytology report of either papillary thyroid carcinoma or Langerhans cell histiocytosis. The latter diagnosis was confirmed on histopathology and immunohistochemical staining for S-100 protein. Intracellular Birbeck granules were also demonstrated by electron microscopy. The disease progressed over a 10-week period to involve the kidneys, resulting in renal dysfunction. CONCLUSION: Synchronous or metachronous involvement of the hypothalamus and thyroid gland by Langerhans histiocytosis could not be excluded in the present case, with subsequent progression to involve other organs. This was an unusual presentation of the disease in an adult.     

Langerhans cell histiocytosis in lymph nodes. Cytomorphologic diagnosis and pitfalls

OBJECTIVE: To delineate the cytomorphology of Langerhans cell histiocytosis (LCH) in lymph nodes. STUDY DESIGN: Nine histologically documented LCH cases with a prior lymph node aspirate and five more cases in which a cytologic diagnosis of LCH was rendered in a background of corroborative clinical and radiologic findings were included in a retrospective study over a 12-year period (January 1988-January 2000). Papanicolaou- and May-Grünwald-Geimsa-stained smears were reviewed by two independent observers. Staining for S-100 protein was available in four cases. RESULTS: Nine cases had multisystem involvement, while in five cases only lymph nodes were involved. The ages ranged from 5 months to 27 years, with 11 males and 3 females. An initial cytologic diagnosis of LCH had been rendered in six, suspected in four and missed in four. On review, all were reclassified as LCH except two cases, which were still thought to be reactive and necrotizing lymphadenitis. The pathognomic feature of LCH, the "LCH cell," was identified in 12 of 14 cases along with varying numbers of eosinophils, polymorphs and lymphocytes. Giant cells were seen in six cases, and plasma cells were rarely seen. CONCLUSION: Lymph node involvement by LCH can be identified by fine needle aspiration in 85% of cases. The presence of the LCH cell is a must. The differentials to be considered are dermatopathic lymphadenitis, sinus histiocytosis with massive lymph-adenopathy, Hodgkin's lymphoma and malignant histiocytosis.     

Mitotic histiocytes and intranuclear Langerhans cell granules in histiocytosis X

Several mitotic histiocytes containing Langerhans cell granules were found in the lymph nodes of Letterer-Siwe disease. Some histiocytes of Hand-Schüller-Christian disease contained Langerhans cell granules within the nuclei. These Langerhans cell granules were not in 'nuclear pseudo-inclusions,' but were freely scattered inside the nuclei. We suggest that the Langerhans cell granules may get trapped in the nucleus during mitosis, since several investigators have suggested that mitosis causes other intranuclear organelles to get trapped. We also speculate that cells containing Langerhans cell granules may divide and increase by mitosis.     

Fine needle aspiration cytology of Langerhans cell histiocytosis of the thyroid. A case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) of the thyroid is a rare condition, and fine needle aspiration cytology (FNAC) of this entity has rarely been described. CASE: FNAC was done on a 3-cm-diameter thyroid swelling in the left lower lobe of the thyroid gland. Smears showed a large number of lymphocytes, eosinophils, thyroid follicular cells and discrete, large cells with prominent nuclear grooves. Mitotic activity was frequent. A cytologic diagnosis of LCH was offered. Subtotal thyroidectomy was performed, and the cytologic diagnosis was confirmed by histology. CONCLUSION: LCH of the thyroid has certain salient diagnostic features. The presence of histiocytes with prominent nuclear grooves, reactive lymphoid cells and eosinophils along with benign thyroid follicular cells should raise the suspicion of this rare entity on FNAC smears of the thyroid.     

Langerhans's cell histiocytosis in old subjects: two rare case reports and review of the literature

doi: 10.1111/j.1741‐2358.2012.00629.x Langerhans’s cell histiocytosis in old subjects: two rare case reports and review of the literature Background: Langerhans cell histiocytosis (LCH) is a proliferative disease of histiocyte‐like cells that generally affects children; LCH onset is rare in adults; immunohistochemistry is essential to obtain the correct diagnosis, and treatment protocols are controversial. Objective: To describe two new cases of adult onset oral LCH. Case reports: Case 1: a 71‐year‐old woman, complaining of diffuse oral pain, presented with erythematous mucosal lesions; the panoramic radiograph and CT scan showed multiple mandible radiolucent areas. Immunohistochemical assay for S‐100, CD1a and langerin test was essential in reaching the correct diagnosis. Case 2: a 77‐year‐old female patient presented with a non‐painful, non‐bleeding, slightly elevated erythematous palatal lesion of 6 months duration, together with a genital vulvar lesion of uncertain nature. The pathology confirmed the diagnosis of LCH. Many therapies (etoposid, radiotherapy) could induce only a clinical partial remission; Cladribine induced a complete recovery. Conclusion: The first case was difficult to diagnose: the clinical presentation and course of the disease (LCH) in the elderly are multiple and unpredictable. An immunohistochemistry study is often essential to obtain the correct diagnosis. The second case required several therapeutic interventions: even though some cases regress spontaneously, others require systemic chemotherapy.     

Radiation diagnosis of Langerhans cell histiocytosis (LCH) of lung

The authors studied the pattern of X-ray changes detectable in the lungs of 41 patients with LCH. The results of classical X-ray study were supplemented by the data of computed tomography, ultrasonography, and 99mTc and 67Ga citrate radioisotopic studies. The diagnostic values of these techniques were compared. X-ray syndromes of changes in the lung in LCH were found to be interstitial, interstitial and granulomatous, tumorous (focal). The authors emphasize the multisystematic character of a lesion, the phasic nature and progression of the disease into fibrosis.     

Evidence that Langerhans cells in adult pulmonary Langerhans cell histiocytosis are mature dendritic cells: importance of the cytokine microenvironment.

Because Langerhans cells (LC) in peripheral tissues are generally "immature" cells with poor lymphostimulatory activity, the contribution of immune responses initiated by LC to the pathogenesis of pulmonary LC histiocytosis (LCH) has been uncertain. In this study we demonstrate that LC accumulating in LCH granulomas are phenotypically similar to mature lymphostimulatory dendritic cells present in lymphoid organs. LC in LCH granulomas intensely expressed B7-1 and B7-2 molecules, whereas normal pulmonary LC and LC accumulating in other pathologic lung disorders did not express these costimulatory molecules. The presence of B7+ LC in LCH granulomas was associated with the expression in these lesions, but not at other sites in the lung, of a unique profile of cytokines (presence of GM-CSF, TNF-alpha, and IL-1beta and the absence of IL-10) that is known to promote the in vitro differentiation of LC into cells expressing a lymphostimulatory phenotype. Finally, LCH granulomas were the only site where CD154-positive T cells could be identified in close contact with LC intensely expressing CD40 Ags. Taken together, these results strongly support the idea that an abnormal immune response initiated by LC may participate in the pathogenesis of pulmonary LCH, and suggest that therapeutic strategies aimed at modifying the lymphostimulatory phenotype of LC may be useful in the treatment of this disorder.     

Langerhans cell histiocytosis of the thyroid diagnosed by fine needle aspiration cytology. A case report

BACKGROUND: Langerhans cell histiocytosis rarely involves the thyroid gland even in patients with multifocal disease. Unifocal disease apparently confined to the thyroid is even more rare. CASE: A 30-year-old woman presented with a 6-cm mass in the right and a 3-cm mass in the left lobe of the thyroid. Fine needle aspiration cytology showed isolated, loose aggregates and histiocytelike cells with grooved or contorted nuclei mixed in varying proportions with many mature eosinophils, scattered and small lymphocytes, multinucleated giant cells and foamy histiocytes. CONCLUSION: The cytologic features of Langerhans cell histiocytosis are characteristic. A fine needle aspiration cytology diagnosis is confirmed by histopathologic studies, imunohistochemical staining and ultrastructural studies.     

FNAC of Bacillus- Calmette- Guerin lymphadenitis masquerading as Langerhans cell histiocytosis

Bacillus Calmette Guerin (BCG) lymphadenitis is a well known entity. Disseminated BCG infection usually presents as generalized lymphadenopathy, skin rash and hepatosplenomegaly and at times, can pose a diagnostic challenge to clinicians. There are only a few published studies on the cytological findings of BCG lymphadenitis. In this letter we report the fine needle aspiration cytology (FNAC) of BCG lymphadenitis clinically masquerading as Langerhans cell histiocytosis (LCH). FNA smears showed sheets of foamy macrophages and many polymorphs in a dirty necrotic background with many macrophages as well as polymorphs showing negatively stained rod like structures within their cytoplasm. Zeihl Neelson stain revealed that these cells were heavily loaded with acid fast bacilli (AFB). In the index case, AFB were also seen within the cytoplasm of polymorphs, which has not been documented earlier in the literature.     

Granular cell tumour of the soft tissues: a case report and literature review

Granular cell tumours (GCT) of the soft tissues are rare benign tumours but some time may be difficult to distinguish from malignant neoplasms. It is important that clinicians are aware of their existence. We present a new case of GCT of the soft tissues followed by a brief review of literature.     

Increased blood myeloid dendritic cells and dendritic cell-poietins in Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH), previously known as histiocytosis X, is a reactive proliferative disease of unknown pathogenesis. Current therapies are based on nonspecific immunosuppression. Because multiple APCs, including Langerhans cells and macrophages, are involved in the lesion formation, we surmised that LCH is a disease of myeloid blood precursors. We found that lin(-) HLA-DR(+)CD11c-+ precursors of dendritic cells, able to give rise to either Langerhans cells or macrophages, are significantly (p = 0.004) increased in the blood of LCH patients. The analysis of serum cytokines in 24 patients demonstrated significantly elevated levels of hemopoietic cytokines such as fms-like tyrosine kinase ligand (FLT3-L, a dendritic cell-mobilizing factor, approximately 2-fold) and M-CSF ( approximately 4-fold). Higher levels of these cytokines correlated with patients having more extensive disease. Serum levels of FLT3-L and M-CSF were highest in high risk patients with extensive skin and/or multisystem involvement. Finally, patients with bone lesions had relatively higher levels of M-CSF and of stem cell factor. Thus, early hemopoietic cytokines such as FLT3-L, stem cell factor, and M-CSF maybe relevant in LCH pathogenesis and might be considered as novel therapeutic targets.     

Fine needle aspiration of Langerhans cell histiocytosis of the lymph nodes. A report of six cases

BACKGROUND: Fine needle aspiration (FNA) diagnosis of Langerhans cell histiocytosis (LCH) of the lymph nodes has been described rarely. CASES: LCH was confined to the lymph nodes in six children. The FNA smears showed high cellularity composed of many isolated Langerhans cells (LCs) with nuclear grooves and intranuclear inclusions. Also seen were numerous eosinophils, lymphocytes, giant cells, dendriticlike cells, macrophages and Charcot-Leyden crystals in a background of eosinophilic granules. Immunohistochemical study revealed a positive reaction with S-100 protein. CONCLUSION: The presence of LCs with nuclear grooves, eosinophils, giant cells and a positive reaction with S-100 protein aided the diagnosis of LCH of the lymph nodes. Charcot-Leyden crystals, intranuclear inclusions and dendriticlike cells were seen in this study. These findings have not been reported before in lymph node FNA smears of LCH.     

Cytology of primary cutaneous Langerhans cell histiocytosis with a malignant phenotype. A case report

BACKGROUND: Langerhans cell histiocytosis (LCH) is a proliferative disorder of Langerhans cells, but the nature of LCH, whether reactive, benign, or malignant and neoplastic, is controversial. We encountered a case of LCH showing a malignant phenotype initially localized in the skin of an elderly woman. Since there is no other report on the cytologic appearance of primary cutaneous LCH or on LCH with a malignant phenotype, we compared the cytologic features of this case with those of benign cases at other sites reported in the literature. CASE: A 74-year-old woman presented with a gradually enlarging and partially ulcerated skin lesion expanding both sides of her right hand. On histologic and ultrastructural analyses of surgically resected tissue, we diagnosed the lesion as Langerhans cell histiocytosis originating in the skin. Although the patient had no recurrence or metastases for six months after surgical resection of the primary skin lesion and radiation therapy, the tumor extended multisystemically, and the patient died of multiple organ failure 14 months after the initial diagnosis. CONCLUSION: Imprint and scrape cytology of multiple skin lesions six months after surgery was useful in immediately diagnosing the recurrent LCH. The tumor cells had indented, twisted or grooved nuclei, and some had intranuclear inclusions. Immunocytochemically the cells were positive for CD1a and S-100 protein. Numerous eosinophils were seen in the background.     

Langerhans cell histiocytosis reveals a new IL-17A-dependent pathway of dendritic cell fusion

IL-17A is a T cell-specific cytokine that is involved in chronic inflammations, such as Mycobacterium infection, Crohn's disease, rheumatoid arthritis and multiple sclerosis. Mouse models have explained the molecular basis of IL-17A production and have shown that IL-17A has a positive effect not only on granuloma formation and neurodegeneration through unknown mechanisms, but also on bone resorption through Receptor activator of NF-kappaB ligand (RANKL) induction in osteoblasts. Langerhans cell histiocytosis (LCH) is a rare disease of unknown etiology, lacking an animal model, that cumulates symptoms that are found separately in various IL-17A-related diseases, such as aggressive chronic granuloma formation, bone resorption and soft tissue lesions with occasional neurodegeneration. We examined IL-17A in the context of LCH and found that there were high serum levels of IL-17A during active LCH and unexpected IL-17A synthesis by dendritic cells (DCs), the major cell type in LCH lesions. We also found an IL-17A-dependent pathway for DC fusion, which was highly potentiated by IFN-gamma and led to giant cells expressing three major tissue-destructive enzymes: tartrate resistant acidic phosphatase and matrix metalloproteinases 9 and 12. IFN-gamma expression has been previously documented in LCH and observed in IL-17A-related diseases. Notably, serum IL-17A-dependent fusion activity correlates with LCH activity. Thus, IL-17A and IL-17A-stimulated DCs represent targets that may have clinical value in the treatment of LCH and other IL-17A-related inflammatory disorders.