Papillary thyroid carcinomas with and without BRAF V600E mutations are morphologically distinct.

AIMS: The BRAF V600E mutation resulting in the production of an abnormal BRAF protein has emerged as the most frequent genetic alteration in papillary thyroid carcinomas (PTCs). This study was aimed at identifying distinctive features in tumours with and without the mutation. METHODS AND RESULTS: Thirty-four mutation-positive and 22 mutation-negative tumours were identified by single-strand conformation polymorphism of the amplified BRAF V600E region in the tumour DNA. Mutation-positive tumours were more common in patients older than 45 years (24/33, P = 0.05), in classic (23/30, P = 0.01), tall cell (4/5) and oncocytic/Warthin-like (2/2) variants of PTC, and in subcapsular sclerosing microcarcinomas (4/4). In contrast, all 12 follicular variants (P < 0.0001) and two diffuse sclerosing variants were negative for the mutation. Mutation-positive tumours displayed infiltrative growth (32/34, P = 0.02), stromal fibrosis (33/34, P < 0.001), psammoma bodies (17/34, P = 0.05), plump eosinophilic tumour cells (22/34, P = 0.01), and classic fully developed nuclear features of PTC (33/34, P = 0.0001). Encapsulation was significantly associated with mutation-negative tumours (15/22, P = 0.02). CONCLUSIONS: BRAF V600E mutation-positive and negative PTCs are morphologically different. Recognition of their morphology may help in the selection of appropriate tumours for genetic testing.

Peritoneal tuberculosis: A case report on a rare cause of tumor marker elevation.

Peritoneal tuberculosis (TB) is a rare extrapulmonary manifestation of TB with non-specific clinical characteristics which can produce test results mimicking malignancy and granulomatous peritonitis. This case describes a Filipino 59-year-old, nulliparous woman who was admitted with abdominal pain, ascites, and an elevated CA-125 level. Radiographically, peritoneal nodules were visualized and initial suspicion was high for malignancy. Following a bilateral salpingo-oophorectomy and peritoneal biopsy, histology was negative for malignancy but revealed non-caseating granulomas. She was discharged then readmitted with progressive abdominal pain, and a repeat laparoscopic biopsy yielded specimens with growth of acid-fast bacilli (AFB). A delay in diagnosis and treatment of tuberculous peritonitis increases mortality rates, making early diagnosis with laparoscopic biopsy of paramount importance in prompt diagnosis and initiation of therapy. This patient was initiated on standard anti-TB therapy and experienced no complications.

Primary, non-exophytic, optic nerve germ cell tumors.

Tumors of the optic chiasm are relatively uncommon and usually associated with phakomatoses such as neurofibromatosis. Even more rare is the presentation of a primary, non-exophytic, isolated optic chiasm germ cell tumor (GCT). These tumors have imaging characteristics nearly indistinguishable from optic chiasmatic gliomas (OCGs). Herein we describe two cases of young men who presented with similar findings of progressive, painless visual loss and hypothalamic-pituitary-adrenal axis dysfunction including diabetes insipidus. Brain imaging was non-diagnostic and suggestive of an OCG. Pathology demonstrated GCTs in each case highlighting the importance of biopsy confirmation of the diagnosis. Both patients underwent a pterional craniotomy and sub-frontal approach to the optic chiasm. The chiasm was diffusely enlarged and discolored in each case without evidence of sellar, suprasellar or perichiasmatic pathology. Pathology demonstrated a malignant mixed GCT in the first patient and a germinoma in the second. This case series highlights the importance of tissue biopsy for patients with progressive symptoms from optic chiasm tumors. Furthermore, this is the first report of a primary, non-exophytic malignant mixed GCT. As the treatment regimens differ widely between optic chiasm GCTs and chiasm gliomas, tissue diagnosis is important.

Cytoplasmic vacuolization: an under-recognized cytomorphologic feature in endocrine tumors of the pancreas.

The diagnosis of pancreatic endocrine neoplasm (PEN) is often straightforward; however, cytomorphologic variants may impose a diagnostic challenge, particularly in small biopsies such as fine-needle aspiration (FNA). Here we describe prominent fine cytoplasmic vacuoles in three cases of PENs which were initially evaluated by endoscopic ultrasound-guided FNA. The clinicopathologic features and diagnostic pitfalls of this cytomorphologic variant were discussed. Awareness of this rare cytomorphologic feature with application of immunocytochemical studies is crucial for rendering an accurate diagnosis and avoiding diagnostic pitfalls.

Identification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma.

BACKGROUND: The identification of molecular alterations has an important therapeutic implication in patients with lung adenocarcinomas. In the current study, the authors evaluated their experience with the identification of epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and anaplastic lymphoma kinase (ALK) gene rearrangement using cytological specimens of primary and metastatic lung adenocarcinoma. METHODS: A total of 54 cases of lung adenocarcinomas (11 primary and 43 metastatic tumors) in which molecular tests were performed were retrieved. Molecular tests were performed on the cell block material of 19 effusions and 35 fine-needle aspirates. EGFR mutation was evaluated by polymerase chain reaction sequencing analysis of exons 18, 19, 20, and 21. KRAS mutation was tested using polymerase chain reaction-single-strand conformational polymorphism analysis of codons 12 and 13. ALK gene rearrangement was evaluated by fluorescence in situ hybridization using an ALK break apart probe. RESULTS: Molecular tests were successful in 49 of 54 cases (91%). Evaluation of EGFR mutation, KRAS mutation, and ALK gene rearrangement were performed in 49 cases, 14 cases, and 22 cases, respectively. EGFR mutations were found in 14 of 49 cases (29%), including 5 primary and 9 metastatic tumors. Three metastatic/recurrent adenocarcinomas demonstrated an additional EGFR T790M mutation that was not identified in the original specimens. KRAS mutation was detected in 3 of 14 cases (21%) including 1 primary and 2 metastatic tumors. ALK gene rearrangement was evident in 3 of 22 cases (14%), all of which were metastatic tumors. CONCLUSIONS: The results of the current study have demonstrated the feasibility of using cytological specimens for EGFR mutation, KRAS mutation, and ALK gene rearrangement analysis. Repeating molecular testing in metastatic/recurrent lung adenocarcinomas may uncover newly acquired molecular alterations.

Addenda in pathology reports: trends and their implications.

Addenda are typically used to report results of additional studies that are delayed relative to histopathologic studies. However, the frequency and pattern of use of addenda have not been previously reported. We studied the dynamics of addenda creation within the same month at 5-year intervals during a 15-year period at our institution. The number of addenda and type and impact of information communicated in addenda were assessed in the month of July in 1993, 1998, 2003, and 2008, and the possible role of addenda in quality improvement was evaluated. Cases with addenda increased from 0.9% in 1993 to 8.6% in 2008. In 5.6% of addenda, there was information that might have been better reported in an amendment, suggesting that criteria for amendments need to be universally implemented. Charting trends and types of addenda offered opportunities for quality improvement by identifying weaknesses in the workflow organization of the laboratory.

Pleomorphic adenoma arising in an incidental midline isthmic thyroid nodule: a case report and review of the literature.

Ectopic salivary gland tissue is common in the head and neck, usually associated with lymph nodes in lateral areas. It is rarely noted in the thyroid gland. Here we report the first case of a pleomorphic adenoma presenting as a midline nodule in the isthmus of thyroid in a 66-year-old man. We propose the possibility of origin in ectopic salivary gland tissue that may have aberrantly migrated with the median anlage from the foramen cecum in the base of the tongue during embryogenesis.

Primary myxopapillary ependymoma of the medulla: case report.

OBJECTIVE: Myxopapillary ependymoma is a subclassification of ependymoma that is thought to be nearly exclusive to the conus medullaris or filum terminale. Primary intracerebral or brainstem myxopapillary ependymomas are rare. CLINICAL PRESENTATION: An 8-year-old child presented with a 5-month history of nausea and vomiting and a 1-week history of headache. Magnetic resonance imaging revealed a nodular mass in the medulla with an associated cyst extending into the fourth ventricle. INTERVENTION: A suboccipital craniotomy was performed, and a gross total resection of the lesion and cyst was achieved. Histological examination confirmed the diagnosis of myxopapillary ependymoma. A discussion of other reported cases of extraspinal myxopapillary ependymomas is presented. CONCLUSION: This is the first report of a case of myxopapillary ependymoma, confirmed by histology, in the medulla. Although rare, myxopapillary ependymomas outside of the filum terminale do exist.