Metastatic hepatocellular carcinoma mimicking acinic cell carcinoma of the parotid gland: a case report.

BACKGROUND: Fine needle aspiration (FNA) is becoming increasingly important in the diagnosis of salivary gland lesions. One of the diagnostic difficulties that arise from FNAs is the distinction between primary and metastatic tumors. We describe a case where a right cheek/parotid mass was originally diagnosed as acinic cell carcinoma (ACC) upon biopsy. Later, an FNA resampling of the mass was diagnosed as hepatocellular carcinoma (HCC), and indeed, a subsequently performed computed tomography scan showed that the patient had a previously unknown liver mass. CASE: A 75-year-old man presented with a pathologic mandibular fracture. An initial needle core biopsy of the lesion showed neoplastic cells with abundant granular cytoplasm and prominent nucleoli and was diagnosed as ACC. The patient shortly thereafter developed an abdominal lesion that upon FNA was found to be cytologically similar to the parotid mass. Immunohistochemical stains showed that the abdominal mass was Hep Par 1 positive, and HCC was diagnosed. An FNA resampling of the parotid lesion was then performed, and stains showed that it was also Hep Par 1 positive. The lesion was rediagnosed as metastatic HCC and not ACC. Radiologic scans of the patient then showed a liver mass as well as multiple bony lesions. CONCLUSION: A right cheek/parotid mass initially diagnosed as ACC was later found to be metastatic HCC. At times, the judicious use of immunohistochemical stains is necessary to distinguish primary salivary gland neoplasias from metastatic tumors.

Quantitative BCR-ABL1 RQ-PCR fusion transcript monitoring in chronic myelogenous leukemia.

The reciprocal Philadelphia translocation between chromosomes 9 and 22 [t(9;22)(q34;q11)] creates a BCR-ABL1 fusion protein that occurs in approximately 95% of cases of chronic myelogenous leukemia (CML), 15% of cases of adult acute lymphoblastic leukemia, and 5% of adult cases of acute myeloid leukemia. The BCR-ABL1 protein is a constitutively activated tyrosine kinase that induces and maintains the neoplastic phenotype in these leukemias. PCR-based methods to identify and quantitate the tumor-specific BCR-ABL1 RNA have been shown to be an ultrasensitive diagnostic/prognostic tool for Philadelphia-positive leukemias. A novel tyrosine kinase inhibitor (TKI), imatinib, has been confirmed as an effective targeted treatment in most CML patients. A consensus goal for TKI treatment is to achieve a major molecular response (MMR), defined as a 3-log (1,000-fold) reduction in BCR-ABL1 transcripts. Patients who achieve an MMR have been shown to have a significantly reduced risk of disease progression. Conversely, increasing post-therapy BCR-ABL1 RNA levels convey a significantly increased risk of disease progression. The early identification of these high-risk patients may allow early changes to the therapeutic strategy, before frank relapse. Thus, quantitative measurement of BCR-ABL1 transcripts in blood and bone marrow both aids in the initial diagnosis of CML and is essential for routine post-therapy minimal residual disease monitoring. We describe here a method for quantitating BCR-ABL1 transcripts in peripheral blood or bone marrow of CML patients using real-time quantitative reverse transcription PCR (RQ-PCR).

Detection of BCR-ABL1 kinase domain mutations causing imatinib resistance in chronic myelogenous leukemia.

The reciprocal translocation between chromosomes 9 and 22 [t(9;22)(q34;q11), Philadelphia chromosome] creates a BCR-ABL1 fusion protein that occurs in approximately 95% of cases of chronic myelogenous leukemia (CML), 15% of cases of adult acute lymphoblastic leukemia, and 5% of adult cases of acute myeloid leukemia. The BCR-ABL1 protein is a constitutively activated tyrosine kinase that induces and maintains the neoplastic phenotype in these leukemias. PCR-based methods to identify and quantitate the tumor-specific BCR-ABL1 RNA have been shown to be an ultrasensitive diagnostic, prognostic, and monitoring tool for Philadelphia-positive leukemias. A novel tyrosine kinase inhibitor (TKI), imatinib, has been confirmed as an effective targeted treatment in most CML patients. However, a significant minority of patients being treated with imatinib develop resistance to the drug as evidenced by rising BCR-ABL1 levels. The most common mechanism of resistance in these patients is the development of mutations in the BCR-ABL1 kinase domain (KD) that abrogate binding of imatinib. Although KD mutations are quite heterogeneous, the identification of the exact mutation site is clinically important, as some mutations, but not others, can be effectively treated with second-generation TKIs. One mutation, T315I, for example, renders the leukemia resistant to all first- and second-line TKIs. Thus, DNA sequencing of the BCR-ABL1 kinase domain in resistant patients helps identify those who may benefit from a change in TKI agents, or those who should be considered for other therapeutic measures, such as stem cell transplantation. We describe here a method for sequencing the BCR-ABL1 kinase domain in peripheral blood or bone marrow of CML patients.