| Japanese Journal of Clinical Oncology | Pages |
Introduction
Case Report
Pathological Findings
Microscopic Findings
Immunohistochemical Findings
Ultrastructural Findings
Final Diagnosis and Management
Discussion
References
Langerhans' Cell Histiocytosis with Thyroid Involvement Masquerading as Thyroid Carcinoma
INTRODUCTION
Langerhans' cell histiocytosis is a rare disease. In 1953 Lichtenstein coined the term `histiocytosis X' to encompass three disease entities of Langerhans' cells including eosinophilic granuloma of bone, Hand-Schüller-Christian disease (the triad of exophthalmos, diabetes insipidus and multiple bony lesions) and Letterer-Siwe disease (a syndrome of rapid, progressive multiple soft tissue involvement) (1 ). In fact, there is a considerable overlap between these entities. Langerhans' cell histiocytosis with thyroid involvement is extremely rare, with only a small number of documented cases (2 -5 ). It is often associated with a relatively indolent course and on pathologic examination is often confused with poorly differentiated carcinoma of the thyroid (3 ). Microscopically, the Langerhans' cells are typical mononuclear `coffee bean-like' cells with folded and grooved nuclei (6 ). Immunohistochemical study of the Langerhans' cells revealed positive immuno-stain for S-100 protein (7 ). Ultrastructurally, the rod-like or tennis racquet-shaped cytoplasmic sructures called Birbeck granules are regarded as a diagnostic clue of Langerhans' cells (8 ). We report a woman who has Langerhans' cell histiocytosis with thyroid involvement. The clinical course, pathologic pattern and ultrastructural features are discussed.
CASE REPORT
A 28-year-old woman was admitted to our Hospital with the chief complaint of progressive, painful swelling of the gingiva with easy bleeding and loosening of teeth over about one year. She had received total thyroidectomy two years previously due to progressive thyromegaly. The pre-operative thyroid function was normal. The thyroidectomy specimen was at first interpreted as `poorly differentiated carcinoma of the thyroid'. She then received one dose of I131 and took hormone replacement therapy thereafter. During the two years since thyroidectomy, there had been no evidence of local recurrence or distant metastases. This time she visited our Dentistry out-patient department and advanced periodontitis was diagnosed. Oral antibiotics were prescribed but there was no improvement in her symptoms.
On physical examination, severe gingival swelling with a bulging soft tissue mass over her hard palate was identified. The thyroid was impalpable and the regional lymph nodes were not enlarged. There was no tender point over her extremities and trunk. Her eyes were not protruding and the liver and spleen were not enlarged. The hemogram showed WBC 8870/[mu]l, hemoglobin 11.6 g/dl and platelet count 331 000/[mu]l. Differential count of WBC showed Seg/Lympho/Mono/Eo/Baso as 62.5/30.0/5.4/ 1.6/0.5. Serum transaminase and creatinine levels were within normal limits. The urine amount was normal. A gum biopsy was taken for final diagnosis.
Ultrastructural Findings
Ultrastructural examination under electron microscope revealed that the Langerhans' cells have large kidney-shaped or infolded nuclei and various types of Birbeck granules, including rod-like or tennis racquet-shaped forms, with a central `zipper-like' striation in the cytoplasm (Fig. 3 ).
Final Diagnosis and Management
These findings were compatible with a diagnosis of Langerhans' cell histiocytosis with thyroid and gum involvement. Subsequent image studies, including skull film, revealed that the skull and sella turcica were normal but that there was destruction of the maxilla and mandible with floating teeth (Fig. 4 ). Whole body bone scan revealed bony invasion of her hard palate and left mandible, but there was no evidence of distant bony metastases. She received radiotherapy to a total of 1000 cGy in five fractions to her oral cavity and oral chemotherapeutic drugs including cyclophosphamide, 6-mercaptopurine and prednisolone were also prescribed. Painful gingival swelling subsided gradually within two months. She was then followed up at our out-patient department for about one year and there was no evidence of local recurrence.
DISCUSSION
Thyroid involvement by Langerhans' cell histiocytosis is extremely rare, and may easily be confused with poorly differentiated carcinoma of the thyroid (8 ). When a prior diagnosis of Langerhans' cell histiocytosis has been made, a tissue diagnosis of thyroid involved by Langerhans' cell histiocytosis may not be too difficult. However, when thyromegaly is the initial sign of Langerhans' cell histiocytosis, the diagnosis may often be extremely difficult (4 ). Coode et al. described a patient in whom a partial thyroidectomy specimen was initially diagnosed as `poorly differentiated follicular carcinoma of the thyroid'. Subsequent electron microscopic study showed the presence of Birbeck granules found in Langerhans' cell histiocytosis, revealing the true nature of the lesion (8 ). Such conditions occurred in our patient. We suspect that the incidence of thyroid abnormalities due to Langerhans' cell histiocytosis may have been underestimated in the past.
Langerhans' cell histiocytosis of the thyroid may occasionally be associated with hypothyroidism (2 ,16 ) or with a normal thyroid function as in our patient. A thyroid mass or nodule may be present, and a primary neoplasm of the thyroid was often taken into consideration. Fine needle aspiration cytologic study of such nodules may be associated with difficulty in differential diagnosis, including chronic thyroiditis (16 ) or carcinoma of the thyroid, as in our patient.
Microscopically, the Langerhans' cell showed a large histiocyte- like mononuclear cell with a folded or grooved nucleus (6). Eosinophils may aggregate in the lesion and produce an eosinophil abscess-like collection to form an eosinophilic granuloma (10 ). In our patient, a lot of eosinophils had infiltrated in the gingiva, although in the thyroidectomy specimen, the eosinophils were absent. The probable reason that it was so difficult to differentiate Langerhans' cell histiocytosis from poorly differentiated carcinoma of the thyroid in our patient is that the eosinophils were absent from the thyroidectomy specimen. Another probable reason is that Langerhans' cell histiocytosis with the initial manifestation of thyromegaly is too rare to be considered. The clinicopathological features of previously reported cases and of our patient are shown in Table 2 .
Table 2 .
| Investigators | Pathology | Course | |||||
| Disrupt | LC | Eo | Neu | Lym | Plasma | ||
| Teja et al. (2) | + | + | + | + | + | + | Favorable, with hypothyroidism |
| Sinisi et al. (3) | + | + | + | + | - | - | Favorable, with partial DI (pituitary-hypothalamic area involvement) |
| Goldstein et al.(4) | + | + | + | - | + | - | With simultaneous papillary Ca, no recurrence for at least 6 months |
| Coode et al.(8) | + | + | + | - | + | - | Favorable, confined to the thyroid only |
| current case | + | + | - | - | + | - | Favorable, gum involvement, no recurrence for>3 years |
Another useful method of differentiating Langerhans' cells from other mononuclear phagocytic cells is the immunohistochemical study. Langerhans' cells were positive for S-100 protein (6 ,11 ) but other mononuclear phagocytic cells, such as macrophages and monocytes, were not (11 ). However, we should keep in mind that besides the Langerhans' cells, nerve cells and melanocytes were also positive for S-100 protein (7 ).
Ultrastructurally, the presence of the Birbeck granule is an important diagnostic clue of Langerhans' cell histiocytosis. Since Birbeck et al. first report the existence of tennis racquet-shaped organelles in epidermal Langerhans' cells (12 ), controversies about their origin and function have never ceased. Occasionally the membranes of Birbeck granules are found to be continuous with the cell surface, so some investigators favor the cell membrane as the site of its formation (13 ,14 ), but results of some studies do not support this point of view (15 ). The origin of these structures is still not clear.
Langerhans' cell histiocytosis confined to the thyroid is often associated with a relatively indolent clinical course (2 -5 ,8 ). Our patient had Langerhans' cell histiocytosis confined to the thyroid and oral cavity and has remained well for more than three years after local management. There was no evidence of local recurrence or distant metastases for her disease. However, we should keep in mind that the presence of disseminated Langerhans' cell histiocytosis (such as Letterer-Siwe disease) with thyroid involvement had been reported (17 ). Involvement of the hypothalamic-pituitary area, causing diabetes insipidus, has been reported in a patient with Langerhans' cell histiocytosis of the thyroid, too (3 ). Before starting any local treatment, a careful history and physical examination is mandatory to rule out the possibility of disseminated Langerhans' cell histiocytosis.
In summary, in patients with thyromegaly, the possibility of Langerhans' cell histiocytosis, although rare, should be kept in mind. A careful microscopic examination, immunohistochemical and ultrastructural studies are very important to make a correct diagnosis. Langerhans' cell histiocytosis confined to the thyroid is often associated with an indolent clinical course. However, before starting any local treatment, the possibility of systemic Langerhans' cell histiocytosis with the thyroid involvement should be considered.
References
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Copyright© Japanese Journal of Clinical Oncology, 1997.
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