Case No. :	103
Month :	July
Year :	2007
Contributor :	Dr. Sheetal Mahey

Other Cases

Case Report: A 25-year-old woman presented with secondary amenorrhea since three years and swelling on the anterior aspect of neck on the right side since one and a half years. Initially, the swelling was peanut sized and increased to the size of an orange within eight months. The swelling was associated with pain and dysphagia which was more for solids than liquids. Subsequently, the patient developed polydypsia and polyuria. For the past eleven months, she had been suffering from low grade fever associated with loss of weight and appetite.

On examination, the general condition of the patient was fair. The pulse was 82/min, blood pressure 120/80 mm Hg. On local examination, there was a diffuse thyroid swelling, soft in consistency on the right side of the anterior aspect of the neck, along with multiple enlarged cervical lymph nodes. No abnormality was detected on examination of the abdomen, respiratory system, central nervous system and cardiovascular system.

Laboratory investigationsincluding hemogram, renal and liver function tests revealed mild elevation of the ESR but were otherwise within normal limits.

Thyroid profile showed reduced TSH levels.

RADIOLOGICAL FINDINGS:

The first imaging study performed was a frontal X-Ray of the chest. It revealed reticular nodular opacities predominantly in both lower zones of the lung.

Fig: 1

Ultrasonography of the neck was performed using superficial probe of frequency-12 Hz showed a heterogeneous enlargement of thyroid gland (Figs 2A,2B,2C). Power Doppler showed increased vascularity within the lesion (Figs 3A,3B)

Fig: 2A	Fig: 2B
Fig: 2C

Fig: 3A	Fig: 3B

A CT scan of the chest with contrast was performed. This showed patchy centrilobular infiltrates throughout the lung fields with cystic changes best seen in the bases of the lung with evidence of fibrosis and cavitation, sparing the costo-phrenic angles. The apex of lungs was spared.

Fig: 4		Fig: 5

 

In view of polydypsia and polyuria, the possibility of diabetes insipidus was considered and an MRI of the brain was performed.

Multiplanar, multiecho MRI of the brain with contrast with 3mm cuts of the sellar region clearly demonstrated a solid intensely enhancing mass measuring 1.0 x 0.9 x 1.0 cm involving the tuber cinerum abutting the posterior aspect of the optic chiasma. The mammilary bodies were seen posterior to the lesion and appeared uninvolved.

Fig: 6A	Fig: 6B
Fig: 6C	Fig: 6D
Fig: 6E

Additional T1W axial cuts were taken from the neck region. These showed an enlarged thyroid gland more on the right side with intense enhancement on post contrast study.

Fig: 7

A skull radiograph revealed no abnormality.

Histopathology findings: An FNAC was performed from the thyroid swelling. This showed plenty of dissociated histiocytic cells, moderate amounts of cytoplasm and vesicular nuclei many of which appeared bilobed and grooved, with deeply clefted nucleus and abundant granular cytoplasm. The background showed lymphocytes, polymorphs and giant cells. No thyroid follicle cell and colloid was seen. Few macrophages and Charcot Layden crystals were seen. Cytomorphology confirmed the diagnosis of Langerhan’s cell histiocytosis.

Final Diagnosis: All imaging and pathological features were consistent with the diagnosis of Langerhan’s cell histiocytosis with CNS involvement (pituitary stalk).

DISCUSSION:
In 1868, Paul Langerhans discovered the epidermal dendritic cells that now bear his name . The term LCH is generally preferred to the older term, histiocytosis X. Langerhans cell histiocytosis or Histiocytosis X is an uncommon disorder. It is characterized by the special type of cells known as Langerhans cells. It is a granulomatous proliferation of the reticular cells at one or several sites in the reticuloendothelial system, possibly related to prior infection.

Histiocytosis is an `umbrella’ designation for a variety of proliferative disorders of histiocytes or macrophages. It encompasses a group of diverse disorders with the common primary event of the accumulation and infiltration of monocytes, macrophages and dendritic cells in the affected tissue. The clinical presentations vary greatly ranging from mild to life threatening.

TYPES:
Histiocytosis is classified into three types.

• First, are malignant histiocytic disorders, a very few histiocytic lymphomas are clearly malignant.
• Second is histiocytosis of mononuclear phagocytes.
• Between these two extremes is a small cluster of relatively rare conditions, the Langerhans’ cell histiocytosis (also known as Histiocytosis X) characterized by the clonal proliferation of a special type of cell, the Langerhans cell.

Langerhans’ cell histiocytosis:

Langerhan's Cell Histiocytosis – LCH (also known as Histiocytosis X) is a rare disease. Histiocytes are normal cells found throughout the body, in this disease abnormally large numbers are found. LCH is more common in children but it is often seen in adults too.

LCH is divided into two groups:

• single-system LCH , when the disease affects only one part of the body, for example, the skin or the bone
• multi-system LCH , when it affects more than one part of the body.

Langerhans’ cell histiocytosis is sub-divided into three categories:-

(1) Letterer Siwe syndrome which predominantly affects children below five years of age.

(2) Hand Schuller Christian disease which affects children between the age group of 2 and 10 years.

(3) Eosinophillic granuloma affecting children between 5 and 15 years of age.

(4) Hashimoto Pritzker disease (Congenital self healing histiocytosis).

CLINICAL FEATURES:
Clinical manifestations depend on the tissue type affected and to some extent the age - with diffuse severe disease occurring more frequently in younger children than adults. Langerhans cell histiocytosis is an inflammatory disease mostly confined to bone (80%). T his can cause pain in the bone and/or swelling on the skull. If the skin is affected, a skin rash, such as cradle cap and nappy rash may occur. A discharge from the ear or hearing problems can occur if the ear is affected. If soft tissue such as lungs, liver, and spleen are affected, then it can lead to difficulty in breathing, jaundice and poor appetite. The hypothalamic pituitary axis may be involved in rare cases causing hormonal problems, this can lead to diabetes insipidus. Occasionally, other pituitary hormones may be affected causing poor growth or delayed puberty. Children over five years of age, often, have only bone involvement. Young children, especially infants, are more likely to have systemic involvement and a fatal outcome.

Causes: The etiology of LCH remains unknown.

• LC proliferation may be induced by a viral infection, a defect in intercellular communication (T cell–macrophage interaction), and/or a cytokine-driven process mediated by tumor necrosis factor, interleukin 11, and leukemia inhibitory factor.

• Cigarette smoking may play a role as a chronic irritant in the development of eosinophilic granuloma of the lung.

Imaging studies

Plain radiographs:

Radiographically, bone involvement shows multiple lytic lesions and may assume a geographic, permeative or moth-eaten configuration. The borders may be well or poorly defined. In the long bones, endosteal scalloping and medullary expansion are typical. Periosteal reaction is common. In the skull, the edges of the lesion may assume a beveled appearance because of asymmetric destruction of the inner and outer tables of the skull. Most commonly affected bones are skull, mandible, ribs and pelvis. In the mandible, alveolar bone may be destroyed, giving teeth a floating appearance. In the spine, vertebral body involvement usually results in collapse, sometimes to a wafer-thin vertebra plana. As the lesion's activity begins to wane, periostitis disappears, the margins become well-defined and, reactive sclerosis may develop.

Chest radiographs reveal diffuse cystic changes and reticular opacities throughout the lungs predominantly in the apex of the lungs. However, the lung volumes are normal.

Bases of the lungs are usually spared.

CT-Scan (HRCT):

A high-resolution computed tomography (CT) image demonstrates widespread small, thin-walled lung cysts with resultant parenchymal destruction. All lobes are involved with relative sparing of the costo-phrenic angles. Cysts in the apical segments are relatively thick walled.

 In the liver, LCH assumes a nodular appearance. It may also result in periportal fibrosis. LCH in the kidney may cause hydronephrosis from pelvic mass effect. The spleen may be enlarged.

MRI BRAIN:
The pituitary stalk shows thickening and uniform enhancement. The posterior pituitary bright spot is not seen on T1W image in some cases. Cerebral and cerebellar atrophy is often seen. After administration of the contrast agent, there is enhancement of the involved areas.

Most commonly, the hypothalamic-pituitary region is involved, leading to diabetes insipidus (DI). Other involved areas of the brain are cerebellum, basal ganglia, the pons, pineal gland, cerebral hemispheres and ventricles.

Differential Diagnosis:-

Lymphocytic hypophysistis.
Endometritis.
Thyroiditis.
Lymphoma.
AITD with pituitary involvement.
Sarcoidosis.
Tuberculosis.
Idiopathic diabetes insipidus.
Multiple myeloma.

Treatment :
Single-system LCH may disappear on its own without any treatment. This may occur even following a biopsy. In some children, treatment such as surgery and corticosteroids may be effective.

Multi-system disease is usually treated with chemotherapy and corticosteroids. The length of treatment varies from child to child.

In our patient, with a history of amenorrhea and diabetes insipidus, all imaging and pathological findings were consistent with the diagnosis of Langerhan’s cell histiocytosis with pituitary stalk involvement