甲状腺罕见的神经母细胞瘤课件

The thyroid: an extremely rare primary site of neuroblastoma Introductio The thyroid is a rare primary site of neuroblastoma (NB) that has not been described in the literature. Neuroblastoma in adolescents is uncommon , and distant multiple metastases to the skin in children are also rare We describe the unique presentation of NB in the pediatric population wherein an 11-year-old boy was diagnosed with NB of the thyroid with regional lymph node and distant multiple subcutaneous metastases. Case report The 11-year-old boy presented to the pediatrics clinic with complaints of fever and thyroid swelling in the neck for the past 4 months and swelling over the scalp for the past 3 months A, Enlarged thyroid and scalp swelling in an 11-year-old boy. Subsequently, he noticed multiple small areas of subcutaneous abdominal swelling for the preceding 15 days. The patient had no history of exposure to radiation or any significant family or past history. On examination, the area of neck swelling was 5 x 6 cm in size, nodular, and more prominent on the right side. It was firm and moved with deglutition. Scalp swelling was present in the left parietal area. It was 4 x 5 cm in size and soft. The 3 areas of subcutaneous abdominal swelling were 1 x 1 cm each, nontender, and mobile in the epigastric region. There was no palpable lymphadenopathy. On routine hematologic examination, hemoglobin was 11 g%, total leukocyte count was 7000/mm3 of blood with normal differential distribution, and erythrocyte sedimentation rate was increased. A thyroid function test and biochemical tests were within normal limits. X-ray of the skull demonstrated subcutaneous scalp swelling with no bony involvement. Ultrasound examination of the thyroid showed an enlarged right lobe of the thyroid and isthmus showing multiple nodules with multiple enlarged right cervical lymph nodes along with evidence of calcification. Abdominal ultrasound was within normal limits. X-ray of the chest, spine, and pelvis did not reveal any metastatic foci. A tentative clinical diagnosis of malignant thyroid mass with multiple metastases was made Fine-needle aspiration of the thyroid, scalp, and areas of subcutaneous abdominal swelling was done with a 23-gauge needle and 10- mL syringe. Slides were wet fixed and air dried and stained with Papanicolaou and Leishman-Giemsa stains, respectively. Cytomorphology in smears from all 3 sites was identical. The smears were richly cellular The cell population comprise monomorphic small round cells arranged in sheets and solid overlapping clumps with occasional rosette-like formations . These were not Homer-Wright rosettes, as they lacked the central neuropil. The cells had hyperchromatic nuclei with indistinct nucleoli and cytoplasm. B, Smear showing rosette-like structure Thus, a cytologic diagnosis of small round cell tumor with metastases was made, with the possibilities of NB and primitive neuroectodermal tumor (PNET). The thyroid mass was excised, along with the subcutaneous abdominal swelling, and sent for histopathologic confirmation. The enlarged right cervical lymph nodes were not removed. Histologic sections from the thyroid mass revealed a lobulated appearance of the tumor with well- demarcated lobules of tumor cells separated by thin fibrous septa. These cells were monomorphic, small, and round with hyperchromatic nuclei, indistinct cytoplasm, and without discernable nucleoli . Areas of hyalinization and calcification were seen. C, Lobulated appearance of tumor D, Cells are of undifferentiated neuroblastoma. Neuropil and Homer-Wright rosette are absent. Insets: Different area with apparent attempt at differentiation showing cells with vesicular nucleus, prominent nucleoli, and cytoplasmic rim Cells with vesicular nuclei, prominent nucleoli, and with a cytoplasmic rim suggesting an attempt at differentiation were also seen occasionally. Homer-Wright rosette and neuropil matrix were not seen. Normal thyroid tissue was seen at the periphery of the tumor . The areas of subcutaneous abdominal swelling also revealed small round cells with characteristics similar to those seen in the thyroid mass. E, Normal thyroid tissue seen at the periphery of the tumor Immunohistochemistry (IHC) demonstrated strong diffuse cytoplasmic positivity of the malignant small round cells for neuron-specific enolase (NSE) . Periodic acidSchiff (PAS) staining was negative. Subsequently, urinary catecholamine metabolite levels were determined and showed elevated urinary vanillylmandelic acid. Thus, it was a case of undifferentiated NB. In view of the diagnosis of NB, postoperative computed tomographic (CT) scan of the abdomen and thorax was done. The scan was normal and did not reveal any abnormality in the adrenal glands or secondary focus. In addition, a CT scan of the head showed no bony or parenchymal involvement, thereby excluding deeper metastases . F, Immunohistochemical stain against neuron-specific enolase shows diffuse strong positivity of tumor cells Discussion Neuroblastoma is the most common extracranial solid nonlymphoreticular tumor in the pediatric age group .It occur predominantly in early childhood; median age at diagnosis is 2 years . Neuroblastoma in adolescents is uncommon, with less than 5% of cases diagnosed in patients older than 10 years . Neuroblastoma can arise from any site having sympathetic nervous system tissue;retroperitoneum and adrenal glands are the most common locations followed by the thoracopulmonary region, mediastinum, head and neck, and pelvis . Approximately one third of patients present with metastases, with regional lymph nodes, bone marrow, liver, bone, and lungs being the most common metastatic sites Immunohistochemistry with antibodies to NSE is a practical method for distinguishing NB from nonneural round cell tumor in children . The diffuse cytoplasmic positivity of NSE is detected in all NB irrespective of the type of histologic differentiation as was seen in our case where morphologically cells were undifferentiated NB. Because PNET, which is our main differential diagnosis, can also demonstrate positive staining of tumor cells for NSE, the staining with PAS was done and turned out to be negative. Neuroblastoma is always PAS negative and PNET shows positivity, but a high percentage of cases of PNET may actually lack PAS positivity. Therefore, results of IHC were only suggestive of NB rather than establishing a definite diagnosis. Other markers, including CD99 and NB 84, N Myc amplification, and electron microscopy, could not be done because of availability and financial constraints. In our case, morphology was of undifferentiated NB, thereby causing difficulty in differentiating it from PNET on histologic grounds alone. The key to histologic differentiation of NB from PNET is the finding of neurofibrillary matrix and Homer-Wright rosette . It has been noted that Homer-Wright rosettes are identified in only one fourth to one third of cases in cytologic smears of NB .However, neither of these features is seen in undifferentiated NB and as in our case. Thus, it was difficult to exclude PNET on morphology. In c