Fusion gene profile of biphenotypic sinonasal sarcoma: an analysis of 44 cases.

AIMS: Biphenotypic sinonasal sarcoma (SNS) is a locally aggressive tumour that occurs in the sinonasal region. PAX3-MAML3 has recently been identified as a recurrent fusion gene event in this entity; however, a subset of tumours harbour alternative PAX3 rearrangement without the involvement of MAML3. In this study we sought to characterize the molecular profile of a large series of cases, with a special emphasis on tumours with alternative fusions. METHODS AND RESULTS: Forty-four examples of SNS were screened by fluorescence in-situ hybridization and reverse transcription polymerase chain reaction to better characterize its molecular profile and identify potential novel fusion genes. Twenty-four were positive for PAX3-MAML3 (55%), 15 showed rearrangements of PAX3 without MAML3 involvement (34%), one showed rearrangement of MAML3 without PAX3 involvement, and four were negative for the involvement of either gene (9%). Among 15 cases with PAX3 involvement only, three were found to harbour PAX3-FOXO1. Two of these cases arose in the nasal cavities of female patients (aged 31 and 47 years), and one showed bilateral involvement of the nasal cavities of a 35-year-old male. A fourth case involved the skull base of a 47-year-old male, and was positive for PAX3-NCOA1. Patients with fusion-negative tumours were slightly older. CONCLUSION: More than half of the SNSs in this series were positive for PAX3-MAML3. However, a subset of tumours may harbour alternative PAX3 fusion genes or show no involvement of PAX3. Except for a possible weak association between age and molecular profile, the overall morphological and immunophenotypic features of all cases seem to be similar. Because of the rarity of these tumours, the impact of the molecular profile on the clinical course of these tumours remains to be determined.

Phase II trial of intravenous administration of Reolysin(®) (Reovirus Serotype-3-dearing Strain) in patients with metastatic melanoma.

Reovirus, a replication competent RNA virus, has preclinical activity against melanoma lines and xenografts. We conducted a phase II trial of reovirus in metastatic melanoma patients. Patients received 3 × 10(10) TCID50 on days 1-5 of each 28 day cycle, administered intravenously. Twenty-one eligible patients were enrolled. Treatment was well tolerated without any dose reductions having to be implemented. Post-treatment biopsy samples were obtained in 15 patients, 13/15 contained adequate tumor for correlative analysis. In two patients, productive reoviral replication (viral antigen coexpression with tubulin) was demonstrated, despite increase in neutralizing antibody titers. There were no objective responses although 75-90% tumor necrosis, consistent with treatment effect, was observed in one patient who had metastatic lesions surgically removed. Median time to progression and survival were 45 days (range 13-96 days) and 165 days (range 15 days-15.8 months) respectively. In conclusion, reovirus treatment was well tolerated in metastatic melanoma patients; viral replication was demonstrated in biopsy samples. Based on preclinical data showing synergy with taxane and platinum compounds, a phase II combination trial in metastatic melanoma patients is ongoing.

Detection of human papilloma virus and p16 expression in high-grade adenoid cystic carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck, particularly basaloid squamous cell carcinoma, may be difficult to distinguish from high-grade adenoid cystic carcinoma. Evidence of human papilloma virus (HPV) infection, particularly HPV 16, is frequently found in non-keratinizing oropharyngeal squamous cell carcinoma. Immunoreactivity for p16, a surrogate marker for HPV infection, often parallels the HPV infection status in oropharyngeal squamous cell carcinoma. However, the incidence and correlation between p16 expression and HPV infection in high-grade adenoid cystic carcinoma is unknown. Sixteen cases of high-grade adenoid cystic carcinoma, three cases of dedifferentiated adenoid cystic carcinoma and eight cases of low-/intermediate-grade adenoid cystic carcinoma were identified for inclusion in the study. All cases were tested by immunohistochemistry for p16 expression and in situ hybridization for high- and low-risk HPV. Eight cases (100%) of low-to-intermediate-grade adenoid cystic carcinoma were focally positive for p16, all of which were negative for HPV. In all, 14 of 16 cases (88%) of high-grade adenoid cystic carcinoma and three cases (100%) of dedifferentiated adenoid cystic carcinoma were positive for p16; strong and diffuse staining was noted in three cases (3 of 19, 16%). Two cases (11%) of high-grade adenoid cystic carcinoma, which were also diffusely positive for p16, showed the presence of high-risk HPV. These findings suggest that the presence of HPV infection in high-grade adenoid cystic carcinoma is infrequent, even in the presence of p16 immunostaining. Nevertheless, HPV positivity should not be used to exclude the possibility of high-grade adenoid cystic carcinoma when the differential diagnosis includes squamous cell carcinoma. Moreover, although p16 overexpression is often used as a surrogate marker for HPV in squamous cell carcinoma, it cannot be used in this manner in high-grade adenoid cystic carcinoma.

Mucoepidermoid carcinoma of the parotid gland: Twenty-year experience in treatment and outcomes.

BACKGROUND: Parotid gland mucoepidermoid carcinoma (MEC) has published five-year cancer-specific survival (CSS) rates of 77%-97%, with variance related to grade. METHODS: Patients receiving primary surgery for parotid gland MEC from 1995 to 2014 at a tertiary medical center underwent clinical review, histopathologic review, and cytogenetic analysis. Survival outcomes were evaluated. RESULTS: Among 58 patients, T/N/M classification was as follows: T1 in 35 patients, T2 in 14, T4a in 9, N0 in 53, N1 in 2, N2b in 3. Histologic grade was low in 27, intermediate in 17, and high in 12 patients with 98% MAML2 positivity. All patients underwent parotidectomy, and seven patients received adjuvant radiation therapy. CSS was 100% at 5 years and 94.1% at 10 and 15 years. Two patients experienced locoregional recurrence. CONCLUSIONS: Treatment with adequate surgical resection and adjuvant radiation therapy for high-grade or advanced-stage tumors yields excellent survival, independent of clinical stage or pathologic grade.

Increased ERBB2 Gene Copy Numbers Reveal a Subset of Salivary Duct Carcinomas with High Densities of Tumor Infiltrating Lymphocytes and PD-L1 Expression.

Salivary duct carcinoma (SDC) commonly expresses androgen receptor (AR) and HER2, giving rise to treatment implications. SDC may also express programmed-death-ligand-1 (PD-L1), a predictive marker of response to checkpoint inhibitors. PD-L1 can be associated with genomic instability and high density of tumor infiltrating lymphocytes (TILs). Evaluation of HER2 immunohistochemistry (IHC) in SDC is not standardized, and relationships between ERBB2 copy numbers, PD-L1 expression and TILs in SDC are unknown. We evaluated 32 SDCs for HER2, AR and PD-L1 expression (IHC), ERBB2 status (FISH) and TILs (slide review). HER2 was scored with three different systems (breast, gastric, proposed salivary gland). PD-L1 was evaluated with the combined positive score. Most patients were older men, presenting at advanced clinical stage with nodal or distant metastases. During follow-up (mean 5 years, range 6 months to 21 years), 25 of the 32 patients (78%) died of SDC. We propose a HER2 IHC scoring system which accurately predicts underlying ERBB2 amplification or increased copy numbers in SDC. Most tumors had increased ERBB2 copy numbers (19/32 amplification, 6/32 aneusomy), a finding associated with higher TIL densities (p = 0.045) and PD-L1 expression (p = 0.025). Patients with TILs ≥ 40% had better prognoses (Log-Rank p = 0.013), with TILs being favorable prognosticators in univariate analysis (Hazard ratio: 0.18, p = 0.024). A subset of SDCs with increased ERBB2 copy numbers have higher TILs and PD-L1 expression. TILs ≥ 40% are associated with better prognosis.

Human papillomavirus-associated oropharyngeal squamous cell carcinomas: primary tumor burden and survival in surgical patients.

OBJECTIVES: We sought to determine whether the primary tumor burden in oropharyngeal squamous cell carcinoma is lower in tumors positive for human papillomavirus (HPV) or in tumors with a smoking- or alcohol-related cause. METHODS: We retrospectively reviewed medical records of patients at our institution who had squamous cell carcinoma of the palatine tonsils, base of tongue, soft palate, or pharynx from 1995 through 2006. The patients underwent primary surgical therapy. The main outcome measures were the HPV status of tumors and nodes and the survival rates (categorized by HPV status). RESULTS: Of 102 treated patients, 48 (47.1%) had HPV-positive carcinomas. Primary tumor size was not significantly different between HPV-positive and HPV-negative tumors (median, 2.5 versus 2.0 cm; p = 0.43). Patients with HPV had a higher prevalence of neck nodal metastases (35% versus 11%; p = 0.003) and high-grade lesions (83% versus 64%; p = 0.03). CONCLUSIONS: Primary tumor burden was not associated with HPV status. Patients with HPV-positive oropharyngeal squamous cell carcinomas had a higher prevalence of neck nodal metastases and high-grade lesions.

Salivary gland-type lung carcinomas: an EGFR immunohistochemical, molecular genetic, and mutational analysis study.

Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, the two most common being adenoid cystic carcinoma and mucoepidermoid carcinoma. Although they usually have an indolent behavior, adenoid cystic carcinomas can be more aggressive, with 5-year survival as low as 55%. Unfortunately, these tumors do not respond well to chemotherapy. In contrast to the most common subtypes of lung carcinomas, epidermal growth factor receptor studies have not been carried out in this group of tumors. Herein we report a series of 24 cases (12 adenoid cystic and 12 mucoepidermoid carcinomas) tested for epidermal growth factor receptor protein expression, epidermal growth factor receptor gene copy gains, and epidermal growth factor receptor gene mutational status, through immunohistochemistry, fluorescence in situ hybridization, and sequencing of the exons 18-21, respectively. Overall, 91 and 92% of the adenoid cystic carcinomas and mucoepidermoid carcinomas expressed epidermal growth factor receptor protein. Chromosome 7 polysomy occurred in 25% of the cases (four adenoid cystic carcinomas and two mucoepidermoid carcinomas). No epidermal growth factor receptor gene amplification was detected and no mutation was found in exons 18-21 of the epidermal growth factor receptor gene. Immunoexpression of epidermal growth factor receptor in salivary gland-type lung carcinomas is not related to epidermal growth factor receptor gene copy number or mutational status.

Sinonasal melanoma: a clinicopathologic review of 61 cases.

OBJECTIVE: To review the Mayo Clinic experience with sinonasal melanoma. STUDY DESIGN: Retrospective review (case series). SUBJECTS AND METHODS: We identified 61 patients who had melanoma arising from the nasal cavity, paranasal sinuses, or both. All were treated at our institution from 1955 through 2003. Clinical and pathologic data were summarized, and survival curves were generated. RESULTS: The most common symptoms at presentation were epistaxis and nasal congestion. The most common treatment was excision only (48%). The cancer-specific survival rate (ie, rate of death due to disease) was 48.9% and 22.1% at 3 and 5 years, respectively. Median time between diagnosis and death due to disease was 19 months. CONCLUSION: Sinonasal melanoma is a rare but devastating disease. Wide local excision is the treatment of choice, and some patients may benefit from postoperative radiotherapy. Local recurrence and distant metastasis are common. Improved survival depends on better systemic therapies.

Clonal nature of sclerosing polycystic adenosis of salivary glands demonstrated by using the polymorphism of the human androgen receptor (HUMARA) locus as a marker.

Sclerosing polycystic adenosis (SPA) is a recently described, rare lesion of the salivary glands that bears a resemblance to epithelial proliferative lesions of the breast. The true nature of the lesion is unknown, but up to now it has been generally believed to represent a pseudoneoplastic sclerosing and inflammatory process. However, local recurrence developed in about one-third of the cases. Superimposed dysplastic changes ranging from low-grade dysplasia to carcinoma in situ were described in SPA. Although no metastases-related and/or disease-related patient deaths were documented, these clinical and histopathologic features raise the possibility that SPA might represent a neoplastic lesion. Polymorphism of the human androgen receptor locus is most frequently used to assess whether the pattern of X-chromosome inactivation is random or nonrandom, the latter strongly indicating clonality. In this study, the assay was applied to tissue from 12 examples of SPA. Three cases (males) were noninformative and 3 cases (females) could not be analyzed owing to poor quality of DNA, but all the remaining 6 lesions satisfied the criteria for monoclonality. We therefore conclude that the findings in the present study are further supporting evidence that SPA is a neoplasm, and not just a reactive process.

Retrospective study and review of polymorphous low-grade adenocarcinoma.

OBJECTIVES/HYPOTHESIS: We review a single institution's experience with polymorphous low-grade adenocarcinoma. To our knowledge, this is the largest patient series of polymorphous low-grade adenocarcinoma with clinical follow-up in the otolaryngology literature. STUDY DESIGN: We retrospectively identified 19 patients with polymorphous low-grade adenocarcinoma who had adequate clinical follow-up and pathologic specimens available for examination. METHODS: All pathologic materials were reviewed by one head and neck pathologist. RESULTS: The median follow-up was 9.6 years. The most frequently affected sites were the hard palate (12 patients) and soft palate (9 patients). Fifteen patients had their initial treatment at our institution, and four patients presented with a recurrent tumor. Five patients had a local recurrence after surgery; of those patients, two had initially presented with recurrent tumors. Local tumors recurred as late as 15 years after the initial surgery. One patient had regional nodal disease 20 years after the initial procedure, and another had lung metastasis. No patients received chemotherapy. The most common initial diagnoses were polymorphous low-grade adenocarcinoma, adenoid cystic carcinoma, and pleomorphic adenoma. CONCLUSIONS: Polymorphous low-grade adenocarcinoma is an increasingly recognized malignancy that originates predominantly in the minor salivary gland. Our experience confirms good local control after a wide local excision is performed, but local recurrences can occur despite having negative margins after surgery. The delayed local recurrences and regional nodal metastases noted in our series show that prolonged follow-up is needed. This series also reports one of the first pathologically confirmed cases of distant metastasis.

Evaluation of tumor angiogenesis measured with microvessel density (MVD) as a prognostic indicator in nasopharyngeal carcinoma: results of RTOG 9505.

PURPOSE: The objective of this study was to evaluate tumor angiogenesis as measured by microvessel density (MVD) as an independent prognostic factor in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy alone. METHODS AND MATERIALS: Eligible patients included those with NPC treated with radiotherapy. Paraffin blocks of the primary tumor had a hematoxylin and eosin-stained section prepared at the block face. One representative section for tumor was stained for factor VIII-related antigen using a standard immunoperoxidase staining technique. MVD was determined by light microscopy in areas of invasive tumor containing the highest numbers of capillaries and microvessels per area. Individual microvessel counts were made on a 200x field within the area of most intense tumor neovascularization. Results were expressed as the highest number of microvessels identified within any single 200x field. Using a breakpoint of MVD <60 vs. > or =60, the distributions between the two MVD groups were compared by the method of Gray. Overall survival rates were estimated by the Kaplan-Meier method and compared by the log-rank test. A multivariate Cox proportional hazard model was employed to examine the relationship between MVD and disease outcomes while adjusting for other concomitant variables. RESULTS: One hundred sixty-six were eligible, of whom 123 had values determined for MVD. The MVD values ranged from 9 to 243 with a median of 70. In the multivariate analysis of overall survival, distant metastases, and local-regional failure, MVD did not significantly improve the model containing T stage, N stage, age, radiation dose, and World Health Organization class. CONCLUSIONS: We found no significant differences in overall survival, time to distant metastasis, or time to local-regional failure using a breakpoint of MVD <60 vs. MVD > or =60. The study was perhaps limited by the small size of the NPC samples.

Pediatric dermoid cysts of the head and neck.

OBJECTIVE: To review the characteristics and determine treatment outcomes of pediatric dermoid cysts. STUDY DESIGN AND SETTING: Retrospective review of the presentation, diagnosis, treatment, and outcomes of all pediatric dermoid cysts of the head and neck examined between 1980 and 2002 at Mayo Clinic. RESULTS: Forty-nine patients (59% girls) had a dermoid cyst of the head and neck. The median age at diagnosis was 22 months. The most common presenting sign was a palpable mass, noted in 100% of patients. During evaluation, approximately 25 patients (51%) had imaging studies. The most common location of the cysts was periorbital (61%), followed by the neck (18%; including 1 submental cyst). Various surgical approaches were chosen. In 2 patients (4%), the dermoid cyst had an intracranial extension. Only 1 patient experienced recurrence. The median pathologic diameter of the cysts was 1.2 cm. CONCLUSIONS: Dermoid cysts are unusual neoplasms that often present in childhood, with the orbit being the area most commonly affected in the head and neck region. Imaging studies help rule out an intracranial or intraorbital extension. With complete excision, recurrence is unusual. Significance Our review will assist both primary care physicians and subspecialists in diagnosing and treating dermoid cysts.

Primary pulmonary hyalinizing clear cell carcinoma of bronchial submucosal gland origin.

Hyalinizing clear cell carcinoma (HCCC) has only been described in salivary glands of the head and neck. We report a 38-year-old man with a 2.6-cm lung tumor that was growing in a peribronchial location and had morphologic features of HCCC. The tumor cells expressed cytokeratin 7 and keratin AE1/AE3, and the vast majority of tumor cells marked also with p63 and p40. They were negative for cytokeratin 20, S-100, smooth muscle actin, napsin A, and thyroid transcription factor-1. Fluorescence in situ hybridization revealed Ewing Sarcoma Breakpoint Region 1 (EWSR1) rearrangement, and reverse-transcription polymerase chain reaction confirmed the presence of the EWSR1-Activating Transcription Factor 1 (ATF1) fusion transcript, which was subsequently sequenced. The morphologic, immunophenotypic, cytogenetic, and molecular findings together with the patient's history and location of the tumor support a diagnosis of primary pulmonary HCCC of bronchial submucosal gland origin. It is our understanding that this is the first report of HCCC arising as a primary tumor outside the head and neck region.

Reproducibility of 3 histologic classifications and 3 staging systems for thymic epithelial neoplasms and its effect on prognosis.

Data regarding the prognostic significance of the histopathologic classifications of thymic epithelial neoplasms are contradictory, perhaps reflecting issues in reproducibility. We studied the effect of reproducibility of 3 histopathologic classifications on prognosis and investigated the interobserver agreement on invasion and its effect on staging and prognosis. A total of 456 patients who underwent surgery for thymic epithelial neoplasm at Mayo Clinic Rochester (1942 to 2008) were staged (modified Masaoka, proposed Moran, proposed IASLC/ITMIG) and independently classified by 3 thoracic pathologists (World Health Organization, proposed Suster & Moran [S&M], and Bernatz). Interobserver agreement was moderate to substantial for all histopathologic classifications (κ values: 0.65, 0.52, 0.74 for World Health Organization, Bernatz, and S&M, respectively). All histopathologic classifications were significant for overall survival (OS) and disease-free survival (DFS) (all reviewers). If adjusted for Masaoka, only Bernatz classification for one reviewer and all histopathologic classifications for another reviewer were significant for OS. Interobserver agreement for invasion was substantial (κ=0.61) and almost perfect for Masaoka, Moran, and IASLC/ITMIG stage (κ values: 0.85, 0.81, and 0.92, respectively). The correlation coefficient for Masaoka and Moran staging was 0.93. Masaoka and IASLC/ITMIG staging were significant for OS and DFS (all reviewers). If adjusted for any histopathologic classification, Masaoka was significant for OS and DFS (all reviewers). In conclusion, reproducibility of histopathologic classifications has some effect on outcome. S&M is the most reproducible classification. Reproducibility of invasion has no effect on the prognostic value of staging. Masaoka, Moran, and IASLC/ITMIG staging are almost perfectly reproducible. The strong correlation between Masaoka and Moran staging suggests similar prognostic strength.

Small cell carcinoma of the major salivary glands: clinicopathologic study with emphasis on cytokeratin 20 immunoreactivity and clinical outcome.

Small cell carcinomas arising in salivary glands, extremely rare high-grade malignant tumors, are subclassified into neuroendocrine and ductal types. The neuroendocrine type may be segregated further into Merkel cell and pulmonary varieties according to cytokeratin 20 immunoreactivity. Whether subclassification of this tumor group has any biologic or clinical significance is not known. We examined 15 cases (11 men, 4 women; mean age, 66.5 years) of small cell carcinoma of major salivary glands from a single institution and analyzed their clinicopathologic profiles, including immunohistochemical features and prognostic factors. Three fourths of small cell carcinomas showed cytokeratin 20-positive immunostaining, often with a paranuclear dotlike pattern of reactivity. All tumors were immunoreactive for at least 2 of 6 neuroendocrine markers examined, and 6 tumors were also positive for neurofilament, with a paranuclear dotlike pattern. Postoperatively, 9 patients developed metastatic disease, and 10 patients died of disease 2 to 45 months (mean, 15.9 months) after diagnosis. By log-rank analysis, overall survival was reduced significantly for patients with a primary tumor larger than 3 cm in diameter (P = 0.032), negative immunostain reaction for cytokeratin 20 (P = 0.012), and decreased immunoreactivity for neuroendocrine markers (P = 0.034). These results indicate that small cell carcinoma of major salivary glands is a highly aggressive tumor, although the prognosis may be better than for extrasalivary neoplasms. Our data also suggest that most salivary gland small cell carcinomas exhibit neuroendocrine differentiation. Immunohistochemical expression of cytokeratin 20 can be used to classify salivary small cell carcinomas into Merkel cell and pulmonary types and may have prognostic significance.

Mucin-rich variant of salivary duct carcinoma: a clinicopathologic and immunohistochemical study of four cases.

Salivary duct carcinoma is a relatively uncommon aggressive neoplasm, typically found in the parotid glands of older men. The histologic appearance is that of an in situ and invasive high-grade adenocarcinoma, and it closely resembles ductal carcinoma of the breast. Several variants of the latter are very well known, but only papillary, sarcomatoid, and low-grade subtypes have so far been reported in salivary duct carcinoma. This study describes the clinicopathologic and immunohistochemical findings in four examples of an additional previously undescribed variant, rich in mucin. Each tumor showed areas of typical salivary duct carcinoma, but in addition there were lakes of epithelial mucin-containing malignant cells, i.e., mucinous (colloid) carcinoma. All four tumors expressed androgen receptors, cytokeratins, epithelial membrane antigen, gross cystic disease fluid protein-15, and carcinoembryonic antigen, but S-100 protein, other myoepithelial markers, and estrogen and progesterone receptors were negative. The mucin antigen profile showed positivity for MUC2, MUC5B, and MUC6 in all cases but only rare staining with MUC5AC and MUC7. Strong immunohistochemical overexpression of HER2/neu was demonstrated in one tumor, together with amplification by fluorescence in situ hybridization; another case was weakly positive with just one antiserum, but the remaining two tumors were completely negative. Small quantities of mucin have often been described in salivary duct carcinoma but not large extracellular mucinous lakes, which though prominent in the present series, were not as extensive as in mucinous adenocarcinoma. The relatively poor clinical outcome of the patients in our study mirrored that seen in usual-type salivary duct carcinoma and emphasizes the importance of differentiating mucin-rich salivary duct carcinoma from pure mucinous (colloid) adenocarcinoma, a tumor not fully defined, but possibly with a better prognosis.

Invasive micropapillary salivary duct carcinoma: a distinct histologic variant with biologic significance.

An invasive micropapillary component has been described in tumors of several organs and is nearly always associated with aggressive biologic behavior. We present 14 cases of salivary duct carcinoma (SDC) with an invasive micropapillary component (invasive micropapillary SDC) and compare the clinicopathologic findings of these cases with those of cases of conventional SDC. The mean age of the 14 patients (10 men, 4 women) was 65.8 years (range, 26-80 years). The mean size of the tumors was 2.4 cm (range, 1.3-5 cm). The parotid gland was involved in 12 patients and the submandibular gland in 2. Histologically, all tumors had an invasive micropapillary architecture admixed with features typical for SDC. Invasive micropapillary carcinoma was characterized by morula-like small cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells exhibited moderate- to high-grade nuclear features, conspicuous nucleoli, and eosinophilic cytoplasm. This component was distributed diffusely in 9 tumors and focally in 5. Angiolymphatic and perineural invasion was seen in all tumors. A residual pleomorphic adenoma was detected in four tumors. Of the 12 tumors examined, all were diffusely positive for cytokeratin 7 and epithelial membrane antigen (with a distinctive "inside-out" pattern) but negative for cytokeratin 20. Tumors were frequently immunoreactive for BRST-2 (gross cystic disease fluid protein-15) and androgen receptor protein. Aberrant expression of HER-2/neu or p53 was detected in seven tumors each. The mean Ki-67 labeling index was 33.1% (range, 6.3%-61.6%). All 14 patients with invasive micropapillary SDC had cervical or periglandular lymph node metastasis, and this value was significantly higher than for conventional SDCs. Local recurrence developed in 4 patients and distant metastatic disease in 9. Clinical follow-up (mean, 25.5 months) was available for 13 patients: 9 died of disease within 24 months after the diagnosis (mean, 17.6 months), 1 was alive with metastatic disease at 19 months, and 3 were free of disease. Overall survival of these patients with invasive micropapillary SDC was significantly shorter than that of patients with conventional SDC (n = 49) in our series (P = 0.031). Our results suggest that invasive micropapillary SDC is a distinct, aggressive variant of SDC, with a propensity for extensive lymph node metastasis and rapid disease progression.

Dedifferentiation in low-grade mucoepidermoid carcinoma of the parotid gland.

Mucoepidermoid carcinoma (MEC), a common malignant salivary gland neoplasm, is generally divided into low-, intermediate-, and high-grade types according to the histologic features. To our knowledge, the present report describes the first case of dedifferentiation occurring in a low-grade MEC. A 55-year-old man presented with a biphasic neoplasm of the right parotid gland composed of low-grade MEC and dedifferentiated high-grade anaplastic undifferentiated carcinoma. Immunohistochemically, carcinoembryonic antigen expression was restricted to the low-grade MEC portion. The Ki-67-labeling index was higher in the dedifferentiated component than in the low-grade component. On image cytometric analysis, the low-grade MEC was diploid, whereas the dedifferentiated carcinoma was aneuploid. Although the patient was alive 10 years after the initial diagnosis, the tumor has recurred twice, at 3 months and 7 months after the initial resection. It is important to recognize that dedifferentiation can occur in a low-grade MEC, similar to other low-grade salivary gland carcinomas.

Sarcomatoid variant of salivary duct carcinoma: clinicopathologic and immunohistochemical study of eight cases with review of the literature.

Salivary duct carcinoma (SDC) is an uncommon, high-grade tumor. We present 8 cases of sarcomatoid SDC, which has been defined recently as a rare variant of SDC. The 8 patients (5 men, 3 women) had a mean age of 63.6 years. Histologically, all tumors were characterized by a biphasic neoplasm composed of both SDC and sarcomatoid elements. In 3 cases, sarcomatoid components showed osteosarcomatous heterologous differentiation. A residual pleomorphic adenoma was detected in 5 tumors. The sarcomatoid component showed focal immunoreactivity for cytokeratin in 4 cases and epithelial membrane antigen in all 8 cases. Diffuse p53 immunostaining was detected in 3 cases, and it was coexpressed in both components. Our observations support the histogenetic theory of a common origin of the carcinomatous and sarcomatoid populations. Of the 13 patients, including our 8, reported to have sarcomatoid SDC arising in a major salivary gland and for whom long-term follow-up data were available, 7 have died of disease (mean survival, 15.6 months). These results indicate that sarcomatoid SDC is a highly aggressive tumor, similar to conventional SDC.

Mucoepidermoid carcinoma of the parotid gland: the Mayo clinic experience.

OBJECTIVE: To determine clinical and histopathologic features of mucoepidermoid carcinoma of the parotid gland, specifically, the relation of tumor stage and grade and treatment type with clinical outcome. DESIGN: Retrospective clinical and histopathologic review. SETTING: Tertiary care medical center. PATIENTS: From 1940 to 1994, 128 patients were treated at our institution for parotid mucoepidermoid carcinoma. Eighty-nine of these patients had their first treatment at our institution; these cases were chosen for retrospective clinical and histopathologic review. INTERVENTION: A head and neck pathologist independently reviewed the pathology specimens. MAIN OUTCOME MEASURES: Age, symptoms, stage, treatment type, tumor grade, pathological features, disease progression, and survival. RESULTS: Results of clinical staging were: T1 in 56 patients, T2 in 13, T3 in 1, T4 in 15, N0 in 85, N1 in 2, and N2 in 2. No patient had N3 or M1 disease. All patients underwent parotidectomy with or without neck dissection. Seven patients received postoperative radiotherapy. Tumor grade was low in 43 patients (48%), intermediate in 40 (45%), and high in 6 (7%). Only 5 patients had disease progression (local recurrence in 4, regional recurrence in 4, and distant recurrence in 2). At latest follow-up (mean follow-up, 14.7 years), 64 patients were alive without disease, 1 was alive with disease, 2 had died of mucoepidermoid carcinoma, and 22 had died of other causes. The Kaplan-Meier estimated cancer-specific survival rates at 5, 15, and 25 years were 98.8%, 97.4%, and 97.4%, respectively. CONCLUSIONS: In our study, tumor grade and stage appeared to be less important than previously described. With adequate parotidectomy and appropriate neck dissection, patients with mucoepidermoid carcinoma of the parotid gland appear to do well, with few recurrences.