Utility of ALK-1 protein expression and ALK rearrangements in distinguishing inflammatory myofibroblastic tumor from malignant spindle cell lesions of the urinary bladder.

Inflammatory myofibroblastic tumor of the urinary bladder is an unusual spindle cell neoplasm that displays cytologic atypia, infiltrative growth and mitotic activity mimicking malignant tumors, such as leiomyosarcoma, rhabdomyosarcoma and sarcomatoid carcinoma. The objective of this study was to determine if anaplastic lymphoma kinase (ALK-1) protein expression detected by immunohistochemistry and ALK rearrangements detected by fluorescence in situ hybridization (FISH) were useful in distinguishing inflammatory myofibroblastic tumor from malignant spindle cell tumors of the urinary bladder. In inflammatory myofibroblastic tumor, ALK-1 expression was identified in 13 of 21 cases (62%) and ALK rearrangements in 14 of 21 cases (67%). All cases of inflammatory myofibroblastic tumor demonstrating ALK-1 expression, carried ALK rearrangements. One case negative for ALK-1 expression exhibited ALK rearrangement. ALK rearrangements were more common in women (P=0.0032). Leiomyosarcoma, sarcomatoid carcinoma, embryonal rhabdomyosarcoma and reactive myofibroblastic proliferations were negative for ALK-1 protein and ALK rearrangements. Immunohistochemistry using markers of muscle, epithelial, neural, and follicular dendritic cell differentiation showed overlap between inflammatory myofibroblastic tumor with and without ALK gene rearrangements, and between inflammatory myofibroblastic tumor and spindle cell malignancies. However, coexpression of cytokeratin and muscle-specific antigens was unique to inflammatory myofibroblastic tumor, observed in approximately half the tumors. This study indicates that detection of ALK protein and ALK gene rearrangements are useful in distinguishing inflammatory myofibroblastic tumor from spindle cell malignancies in the urinary bladder. Additionally, our findings suggest that ALK rearrangement is the primary mechanism for ALK activation and that inflammatory myofibroblastic tumor likely represents a heterogeneous group of spindle cell proliferations with the majority associated with ALK translocations, and the remaining associated with other etiologies.

Current status of fine needle aspiration for thyroid nodules.

When not to perform fine needle aspiration of a thyroid nodule In summary, FNA of thyroid nodules has become one of the most useful, safe, and accurate tools in the diagnosis of thyroid pathology. Thyroid nodules that should be considered for FNA include any firm, palpable, solitary nodule or nodule associated with worrisome clinical features (rapid growth, attachment to adjacent tissues, new hoarseness, or palpable lymphadenopathy). FNA should also be performed on nodules with suspicious ultrasonographic features (microcalcifications, rounded shape, predominantly solid composition); dominant or atypical nodules in multinodular goiter; complex or recurrent cystic nodules; or any nodule associated with palpable or ultrasonographically abnormal cervical lymph nodes. Finally, FNA should be performed on any abnormal-appearing or palpable cervical lymph nodes. The management of thyroid nodules based on FNA findings is summarized in Table 2. It can be argued that in certain circumstances the results of thyroid FNA do not change the surgical management of a thyroid nodule, and thus preoperative FNA may be unnecessary. These cases include solitary nodules in patients who have a strong family history of thyroid cancer, multiple endocrine neoplasia type II, or radiation to the head and neck. These patients when they have thyroid nodules have at least a 40% risk for thyroid cancer and frequent multifocal or bilateral disease and should undergo total thyroidectomy with or without central neck lymph node dissection. Patients who have multinodular goiter and compressive symptoms, patients who have Graves disease and a thyroid nodule, or patients who have large (greater than 4 cm) or symptomatic unilateral thyroid nodules could also be considered for total thyroidectomy or lobectomy as indicated without preoperative FNA. Finally, patients who have a solitary hyperfunctioning nodule on radioiodine scan and a suppressed TSH have an extremely low incidence of malignancy and may be considered for therapeutic thyroid lobectomy or radioiodine ablation as indicated without undergoing FNA biopsy.