Martin Bullock

Epithelial-myoepithelial carcinoma with high grade transformation.

Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland tumor of presumed intercalated duct origin with a low risk of metastasis and mortality. Factors shown to affect behavior include positive margins, vascular invasion, necrosis, and myoepithelial anaplasia. The latter category and dedifferentiated EMCs have been separated on the basis of presumed myoepithelial versus ductal origin, respectively. Three additional cases of typical EMC with transition to high-grade carcinoma are presented. Two of the tumors were stained with CAM5.2, 34βE12, cytokeratin 14, p63, S100, calponin, smooth muscle actin, and muscle-specific actin. All tumors showed a gradual transition to a high-grade carcinoma from an EMC, each composed of clear cells even in the high-grade regions. One case also showed a discrete area with ductal lumina and another had plasmacytoid morphology. Squamous differentiation was seen in all cases as well. A consistent immunostaining pattern was not noted. Areas with focal lumina were diffusely positive for CAM5.2 only. Areas with clear cells showed patchy S100 positivity only, whereas cytokeratin 14 and 34βE12-stained squamous pearls. The case with plasmacytoid morphology was diffusely positive for p63. No immunoexpression was noted with smooth muscle actin, muscle-specific actin, or calponin. It was not possible to convincingly separate the high-grade component in these cases into ductal dedifferentiated EMC versus myoepithelial. Recently, there has been a move to abandon the term “dedifferentiation” in favor of “high-grade transformation” in other salivary gland malignancies. We report these 3 such cases, review the literature and propose that these lesions be regarded as “EMC with high-grade transformation.”

Complete spontaneous regression of metastatic merkel cell carcinoma: a case report and review of the literature.

Merkel cell carcinoma (MCC) is a rare aggressive primary cutaneous neuroendocrine neoplasm with a high rate of recurrence and metastasis. We report a case of a 94-year-old woman who experienced complete spontaneous regression of metastatic MCC. Nine months after complete excision of the primary MCC on her left eyebrow, metastatic MCC was confirmed with a fine-needle aspiration of a 4-cm mass on the left side of her neck. Three months later the mass had reduced in size to 2 cm and a neck dissection was performed. Her submandibular gland, thoracic duct and 25 lymph nodes were negative for MCC. Two of the lymph nodes, the larger measuring 1.3 cm, contained extensive amounts of fibrosis, with accumulation of macrophages and other chronic inflammatory cells. The literature documents 6 similar cases of complete spontaneous regression of metastatic MCC. The mechanism for regression is not well understood and is thought to involve T-cell-mediated immune response and apoptosis.

Pathologic effects of neoadjuvant cyproterone acetate on nonneoplastic prostate, prostatic intraepithelial neoplasia, and adenocarcinoma: a detailed analysis of radical prostatectomy specimens from a randomized trial.

Neoadjuvant hormonal therapy (NHT; androgen ablation) is used prior to radical prostatectomy (RP) in an attempt to pathologically “downstage” prostatic adenocarcinoma and ultimately to improve disease-free survival. This study describes the pathologic effects of NHT with the antiandrogen cyproterone acetate, 300 mg/day for 12 weeks, on the RP specimens from men with clinically localized (stage T1 or T2) prostatic adenocarcinoma. There were 101 men in the pretreatment group (CPA) and 91 men in a control group who were treated with surgery alone. The prevalence and extent of morphologic effects were recorded for the nonneoplastic prostate, high-grade prostatic intraepithelial neoplasia, and invasive adenocarcinoma. The commonest effects on the nonneoplastic prostate were atrophy and basal cell hyperplasia and prominence. High-grade prostatic intraepithelial neoplasia was more commonly identified in the surgery alone group than the CPA group (p <0.01). In the CPA group, flat and low tufted patterns of high-grade prostatic intraepithelial neoplasia predominated. Following NHT, the adenocarcinoma showed characteristic morphologic alterations, including reduction in cytoplasmic quantity, cytoplasmic vacuolation, nuclear pyknosis, reduced gland diameter, and mucinous breakdown. In many cases there was prominence of collagenous stroma, obscuring malignant glands. Compared with the surgery alone group, the CPA group RP specimens had a significantly lower mean specimen weight (40.3 g vs 46.5 g, p = 0.025) and less tumor extent by several measures. Organ-confined tumor (stage pT2, margin negative) was found in 41.6% of the CPA group compared with 19.8% of the surgery alone group (p = 0.0017). The overall rate of margin positivity was lower in the CPA group (27.7% vs 64.8%, p = 0.001). We consider that the difference in margin positivity is the result of tumor shrinkage with a decreased likelihood of sampling in routine sections. There was no significant difference in the rate of extraprostatic extension between the two groups. There was elevation of the Gleason score in the RP specimens versus baseline biopsy in 60% of the CPA group compared with 33% of the surgery alone group (p = 0.02). The higher rate of elevation in the CPA group largely resulted from an increase in primary or secondary Gleason score 5 tumor, a morphologic artifact introduced by NHT. Because of this, we recommend not giving a Gleason grade to RP specimens following NHT. Monotherapy with CPA has similar pathologic effects on benign and malignant prostate tissue as does dual agent androgen blockade. Prolonged follow-up of these patients is required to determine if NHT with CPA leads to improved disease-free survival.

Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study.

Mammary analog secretory carcinoma (MASC) is a recently recognized low-grade salivary carcinoma characterized by a specific ETV6 rearrangement. We describe 14 new MASCs and examine their immunophenotypic and genetic profiles in the context of look-alikes, namely, low-and high-grade salivary duct carcinoma and acinic cell carcinoma. ETV6 rearrangement, and robust expression of mammaglobin and S100, were demonstrated in 11/11, 14/14, and 12/14 MASCs, respectively. All low-grade salivary duct carcinomas coexpressed S100/mammaglobin (6/6); none harbored ETV6 rearrangements (0/5). Given that S100/mammaglobin coexpression and absence of zymogen granules are features of both MASC and low-grade salivary duct carcinoma, these two are best distinguished histologically. The former is predominantly an extraductal neoplasm with bubbly pink cytoplasm, whereas the latter is a distinct intraductal micropapillary and cribriform process. Querying ETV6 gene status may be necessary for difficult cases. No acinic cell carcinoma expressed mammaglobin (0/13) or harbored an ETV6 rearrangement (0/7); only 1/13 acinic cell carcinomas weakly expressed S100. DOG1 expression was limited or absent among all tumor types, except acinic cell carcinoma which expressed DOG1 diffusely in a canalicular pattern. Therefore, histology and immunohistochemistry (mammaglobin, S100, DOG1) suffices in distinguishing acinic cell carcinoma from both MASC and low-grade salivary duct carcinoma. HER2 (ERBB2) amplification was detected in only 1/10 acinic cell carcinomas, but none of the MASCs or low-grade salivary duct carcinomas tested. High-grade salivary duct carcinomas frequently expressed mammaglobin (11/18) and harbored HER2 amplifications (13/15); none harbored ETV6 rearrangements (0/12). High-grade salivary duct carcinomas can easily be distinguished from these other entities by histology and HER2 amplification.

Transoral laser microsurgery versus radiation therapy for early glottic cancer in Canada: Cost analysis

OBJECTIVE There is debate over whether radiation therapy or transoral laser microsurgery (TLM) is the superior treatment for early glottic cancer. Both offer similar cure rates and posttherapy quality of life. One factor that could decide the optimum therapy is cost. Several studies in Europe and the United States show that TLM is the most cost-effective treatment. The goal of this study was to conduct the first cost analysis in Canada on the treatment of early glottic cancer comparing radiation therapy and TLM. DESIGN AND METHODS The study was conducted retrospectively. TLM and radiation therapy were broken down into individual components, and then the price for each component was summed. SETTING The study was conducted at the Queen Elizabeth II Health Science Centre in Halifax, Nova Scotia. MAIN OUTCOME MEASURES The main outcome measure was total cost. RESULTS It was found that radiation therapy was approximately four times more expensive than TLM. CONCLUSIONS This study suggests that TLM should be the preferred treatment option for treating early glottic cancer in Canada as it is the most economical and has been shown in previous studies to be as effective as radiation therapy in both cure rates and quality of life.

Is preoperative ultrasonography accurate in measuring tumor thickness and predicting the incidence of cervical metastasis in oral cancer

The need for elective neck dissection in patients with early stage oral cancer is controversial. A preoperative predictor of the risk of subclinical nodal metastasis would be useful. Studies have shown a strong correlation between histological tumor depth and the risk of nodal metastasis. To determine if preoperative ultrasonography is an accurate measure of tumor depth in oral carcinoma. To assess if preoperatively measured tumor depth predicts an increased risk of subclinical metastatic neck disease and thus the need for elective neck dissection. Twenty one consecutive patients with biopsy proven squamous cell carcinoma of the tongue/floor of mouth were analyzed prospectively. Each patient received a preoperative ultrasonography to assess tumor depth which was compared to histological measures. Univariate analysis was used to correlate tumor thickness and T stage with neck metastasis. There was a significant correlation between the preoperative ultrasonography and histological measures of tumor depth (correlation coefficient 0.981, P<0.001). The overall rate of lymph node metastasis was 52%. The rate of metastasis was 33% in N0 necks. In the group with tumors<5mm in depth, the neck metastatic rate was 0%, as compared with 65% in the group 5mm. Using univariate analysis tumor depth and T stage were significant predictors of cervical metastasis (P=0.0351 and P=0.0300, respectively). Preoperative ultrasonography is an accurate measure of tumor depth in oral carcinoma. Tumor thickness is a significant predictor of nodal metastasis and elective neck dissection should be considered when this thickness is 5mm.

Calretinin staining facilitates differentiation of olfactory neuroblastoma from other small round blue cell tumors in the sinonasal tract.

Objective:Olfactory neuroblastoma (ONB) is an uncommon malignant tumor of the sinonasal tract and has a wide histologic differential diagnosis that includes other small round blue cell tumors (SRBCTs). Even with the use of immunohistochemistry (IHC), the correct diagnosis may be difficult, especially in small biopsies. The purpose of this study is to determine the usefulness of calretinin and p63 as an aid to distinguish ONB from other sinonasal SRBCTs. Methods:IHC staining for calretinin and p63 was performed on 21 specimens diagnosed as ONB and on 42 other sinonasal SRBCTs. Specimens were retrieved from the files of the QEII HSC, Halifax and UHN, Toronto. Results:All but 1 ONB (20 of 21) showed calretinin staining, with 15 of 21 showing staining in >75% of the tumor area and 18 of 21 showing moderate-to-strong staining intensity. Only pituitary adenomas (3 of 3) and a single case of small cell carcinoma, neuroendocrine type (1 of 2), showed a similar staining pattern. None of the ONBs showed staining for p63. P63 was positive in all cases of nonkeratinizing squamous cell carcinoma (2 of 2) and in single cases of mantle cell lymphoma (1 of 1) and poorly differentiated neuroendocrine carcinoma (1 of 1); however, it inconsistently stained diffuse large B-cell lymphoma (4 of 5), extranodal NK/T-cell lymphoma, nasal type (1 of 4), sinonasal undifferentiated carcinoma (1 of 6), and Ewing sarcoma/primitive neuroectodermal tumor (2 of 6). Conclusions:Calretinin appears to be a useful marker to distinguish ONBs from other SRBCTs of the sinonasal tract, particularly when staining is moderate/strong and extensive. The calretinin-positive, p63-negative phenotype is fairly specific for ONB. The addition of these 2 IHC stains may aid in the diagnosis of sinonasal SRBCTs that are poorly differentiated, have inconclusive conventional IHC, or are found in small biopsies.

Hyperparathyroidism–jaw tumor syndrome

Hyperparathyroidism–jaw tumor (HPT‐JT) syndrome is a rare autosomal dominant multiple tumor syndrome characterized by hyperparathyroidism due to single or multiple‐gland parathyroid tumor(s). Since it was first described in 1990, the genetics underlying the syndrome have been elucidated and typical clinical presentations are becoming clarified as literature describing this rare entity amasses.

Lateral Ectopic Thyroid Goiter with a Normally Located Thyroid

BACKGROUND Midline ectopic thyroid tissue is a common pathological entity. In contrast, laterally located ectopic thyroid tissue with a normally located thyroid gland is a very rare condition in head and neck surgery. SUMMARY We report the association of laterally located multinodular thyroid tissue and a normally located multinodular goiter. A woman was seen in the otolaryngology clinic with a right submandibular mass. Clinical examination and investigations confirmed the presence of a multinodular goiter in an ectopic thyroid gland. CONCLUSION Laterally located ectopic thyroid tissue is a very rare condition. Ectopic thyroid tissues can undergo the same pathological changes as a normally located thyroid gland. Ectopic thyroid goiter together with a normally located multinodular goiter is a rare entity, and this is the first to be reported in North America.

Serum microRNA profiling to distinguish papillary thyroid cancer from benign thyroid masses

ObjectivesPapillary thyroid cancer (PTC) is increasing in incidence. Fine needle aspiration is the gold standard for diagnosis, but results can be indeterminate. Identifying tissue and serum biomarkers, like microRNA, is therefore desirable. We sought to identify miRNA that is differentially expressed in the serum of patients with PTC.MethodsSerum miRNA was quantified in 31 female thyroidectomy patients: 13 with benign disease and 18 with PTC. qPCR results were compared for significant fold-changes in 175 miRNAs, against a pooled control.Results128 miRNA qualified for analysis. There were identifiable fold-changes in miRNA levels between benign and control, and between PTC and control. There were statistically significant fold changes in the level of four miRNAs between benign and PTC: hsa-miR-146a-5p and hsa-miR-199b-3p were down-regulated, while hsa-let7b-5p and hsa-miR-10a-5p were up-regulated.ConclusionsMicroRNA is differentially expressed in the serum of patients with PTC. Serum miRNA has the potential to aid in thyroid cancer diagnosis.