Survival and prognostic factors of salivary gland malignant mixed tumor-not otherwise specified: A population-based analysis.

OBJECTIVE: Malignant mixed tumors of the salivary gland are a group of neoplasms comprised of carcinoma-ex-pleomorphic adenoma, carcinosarcoma, and metastasizing pleomorphic adenoma. An alternative classification, malignant mixed tumor-not otherwise (MMT-NOS), is a diagnosis of exclusion for neoplasms that do not fit the previous histologically profiled subtypes. The objective was to provide a comprehensive assessment of MMT-NOS and determine prognostic factors. METHODS: This retrospective cohort study queried the Surveillance, Epidemiology, and End Results database for patient and tumor characteristics of US patients with MMT-NOS of the major salivary glands from 1973 to 2016. Kaplan-Meier and Cox regression analysis were performed to determine 5-year survival and prognostic factors. RESULTS: 434 patients were identified with a mean age at diagnosis of 61.5 years. The majority of neoplasms were high grade and stage (70.8% grade III/IV; 63.8% stage III/IV). Extraparenchymal extension (40.6%) and lymph node involvement (28.5%) were common; distant metastases (2.4%) were rare. Treatment included surgery (93.0%), radiation (51.6%), and chemotherapy (10.4%). Facial nerve sacrifice was common (50.8%). Median survival was 66.5 months. 5-year overall and disease-specific survival were 65.7% and 83.0%, respectively. In multivariate analysis, nodal involvement (HR 7.0; P < 0.001), surgery-radiation-chemotherapy (HR 6.1; P = 0.02), extraparenchymal extension (HR 2.50; P = 0.04), and tumor size >4 cm (HR 1.3; P = 0.03) were prognostic factors. CONCLUSION: Despite high stage and grade at diagnosis, MMT-NOS portends a good 5-year prognosis and low rate of distant metastasis. Prognostic factors were nodal involvement, tumor size, and extraparenchymal extension.

[Multimodal treatment of malignant mixed Müllerian tumor]. / Malignus kevert Müller-cso-eredetu tumor komplex kezelése.

INTRODUCTION AND AIM: The aim of our study was to evaluate the prognostic factors and treatment options of a very rare and highly aggressive type of uterine neoplasms, the malignant mixed Müllerian tumor, known as carcinosarcoma. METHOD: Between 2009 and 2017, 29 patients were treated with malignant mixed Müllerian tumor. At stage I, surgery and postoperative radiotherapy were performed. At stages II-IV, trimodal treatment (surgery, chemotherapy and radiotherapy) was administered. RESULTS: The average age of patients was 68.51 (49-90) years, mean body mass index was 30.22 (20.90-37.22). We have experienced recurrence of disease after complete resection in 6 cases (4 of 6 patients did not accept radiation therapy). Local recurrence has occurred after an average 15.52 (6-36) months, distant metastasis with an average 19.2 (8-32) months. Overall survival was 11.92 (1-75) months. Six patients are free of tumours at the moment. CONCLUSIONS: As overall survival has not increased in recent decades by using combined chemotherapy, there is no congruent consensus associated with the optimal treatment. The standard surgical treatment is total abdominal hysterectomy with bilateral oophorectomy, although due to high rates of recurrence and metastases, the necessity of lymphadenectomy and postoperative treatment is in the focus of recent studies. Though postoperative irradiation improves local control, the beneficial effect on overall survival is still not proven. Adjuvant chemotherapy decreases the rate of both pelvic and extrapelvic recurrence at the same time, although there is no recommendation for the optimal chemoterapeutic agent. Multimodal therapy should lead to better outcomes. Recently there are many ongoing studies with biologic and target therapies to improve efficiency, however, the relevant results will be disclosed in many years only, due to the small number of patients. Orv Hetil. 2018; 159(19): 741-7747.

Ampullary Mixed Adenoneuroendocrine Carcinoma: Surprise Histology, Familiar Management.

INTRODUCTION: Mixed adenoneuroendocrine carcinoma (MANEC) has recently been defined by the World Health Organization in 2010. These are rare tumors and MANECs of ampullary region are even rarer. Only 19 cases have been reported in literature. We present 3 cases; the largest series, second case of amphicrine tumor and first case associated with chronic pancreatitis. METHODS: Retrospective review of 3 patients who were diagnosed to have ampullary MANEC. RESULTS: All 3 patients were diagnosed preoperatively as neuroendocrine carcinoma and underwent margin negative pancreaticoduodenectomy. The histopathology revealed MANECs of small cell, mixed type in 2 patients and large cell, amphicrine type in 1 patient. The neuroendocrine component was grade 3 in all, the tumor was T3 in 2 and T2 in 1 and all had nodal metastases. Two patients received adjuvant chemotherapy and 2 of them had recurrence at 13 and 16 months. The median survival was 15 months. CONCLUSION: Ampullary MANECs are rare tumors. They are diagnosed on histopathologic examination of the resected specimen. Clinical presentation, management, and prognosis is similar to ampullary adenocarcinoma in literature.

Long-term treatment outcome of minor salivary gland carcinoma of the hard palate.

Minor salivary gland carcinoma of the hard palate is rare, and its long-term survival rate is high, making it difficult to evaluate the prognostic factors and the efficacy of treatment. This study was designed to evaluate the treatment outcome of minor salivary gland carcinoma of the hard palate. 103 cases of minor salivary gland carcinoma of the hard palate treated with surgery alone or underwent surgery combined with post-operative radiotherapy hospitalized in Cancer Center, Sun Yet-Sen University, from 1968 to 2008 were reviewed retrospectively. The most common histologic types were adenoid cystic carcinoma in 48 patients(46.6%), mucoepidermoid carcinoma in 37(35.92%), malignant mixed tumor in 15(14.56%), and acinic cell carcinoma in 3(2.91%). The median follow-up time was 74.83 months (range 0.9-356.57 months). Overall outcomes at 5 and 10 years were overall survival (OS), 77.9% and 65.7%; recurrence-free survival (RFS), 64.4% and 53.2%; and disease specific survival (DSS), 77.9% and 67.7%, respectively. There was no significant difference in overall survival (P=0.52), recurrence-free survival (P=0.762) and disease specific survival (P=0.449) between patients who underwent surgery alone and those who underwent surgery plus post-operative radiotherapy. Surgery has been accepted as the primary treatment for minor salivary gland carcinoma of hard palate. Sufficient surgical excision with adequate margins is essential for a favorable outcome. We advocate using radiotherapy in the post-operative context for patients with poorly differentiated, cervical lymph node metastasis, positive or close margins, and large primary lesions.

Subependymoma revisited: clinicopathological evaluation of 83 cases.

OBJECT: Subependymomas are rare ependymal neoplasms. To date, a large clinicopathologic study of these benign neoplasms treated with modern neurosurgical techniques has not been reported. METHODS: Eighty-three cases of subependymoma were retrieved from the files of the Armed Forces Institute of Pathology. Clinicopathological features were reviewed; chromogenic in situ hybridization analysis for chromosome 22 was performed (n = 8), and patient follow-up was obtained (n = 34). Overall, the patients included 68 males and 15 females, 1.5 to 85 years of age (mean, 51.0 years). Twenty-seven cases were discovered at autopsy and the remaining were surgical specimens (n = 56). Tumors arose in the posterior fossa (n = 43), lateral ventricles (n = 37), spinal cord (2) and only one arose in the temporal horn. Tumors ranged in size from 2.0 mm to 60 mm in greatest dimension (mean, 23.0 mm). Eighteen-percent (15/83) of subependymomas exhibited a mixed histologic pattern; that is, subependymoma together with another glial tumor. The most common mixture (13/15) was subependymoma and ependymoma. Surgical excision was used in all symptomatic patients; 10 patients received radiation. Four patients developed a recurrence due to incomplete excision. All patients were without evidence of disease at the last follow-up: alive (n = 28) or dead (n = 8). CONCLUSIONS: Age is the only variable found to be significantly associated with survival. Currently, surgical methods result in an excellent long-term clinical outcome. Subependymomas do not appear to be associated with NF2 mutations.

Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract.

To further define the clinicopathologic spectrum of epithelial-myoepithelial carcinoma (EMCa), we report the gross, histologic, and immunophenotypic characteristics of 61 tumors seen within a 30-year-period. The mean age at presentation was 60.9 years, with a female predominance (1.5:1). The most common sites were parotid (62.1%), sinonasal mucoserous glands (10.3%), palate (8.6%), and submandibular (8.6%). Most EMCas showed a characteristic nodular/multinodular growth pattern and classic biphasic tubular histology. However, new morphologies in EMCa such as ancient change (8.2%), "Verocay"-like change (3.3%), and sebaceous differentiation (13.1%) were noted. Specific histologic variants were dedifferentiated EMCa (3.3%), oncocytic EMCa (8.2%), EMCa ex pleomorphic adenoma (1.6%), double-clear EMCa (3.3%), and EMCa with myoepithelial anaplasia (3.3%). All cytokeratin cocktails selectively highlighted the epithelial component well. Of the myoepithelial markers, p63, smooth muscle actin and vimentin performed best. Bcl-2 and c-kit were frequently positive (66.7% and 69.2%, respectively). p53 was highly expressed only in 1 dedifferentiated EMCa. The recurrence rate was 36.3% (median disease-free survival 11.34 y), but death was rare with 5-year and 10-year disease-specific survivals of 93.5% and 81.8%, respectively. The most important univariate predictors of recurrence were margin status (log rank P=0.006), angiolymphatic invasion (P=0.002), tumor necrosis (P=0.004), and myoepithelial anaplasia (P=0.038). Thus, EMCa is generally a low-grade tumor with a broader morphologic spectrum than previously thought, with several key features predictive of recurrence. Immunohistochemistry can aid diagnosis by highlighting the biphasic nature of the tumor.

Effective bladder sparing therapy with intra-arterial cisplatin and radiotherapy for localized bladder cancer.

PURPOSE: We evaluated the feasibility and efficacy of the organ preserving strategy of intra-arterial cisplatin and concurrent radiotherapy for localized bladder cancer. MATERIALS AND METHODS: Bladder preservation has been pursued over the decades in treatment regimens featuring radiotherapy alone or in conjunction with single or multiagent chemotherapy. The chemotherapy has consisted almost exclusively of intravenously administered drugs. There are theoretical and clinical data demonstrating a higher concentration of cisplatin within tumors following intra-arterial as opposed to intravenous delivery. This study was performed to evaluate whether this increased concentration would enhance radiosensitization and thereby increase the success of bladder preservation. RESULTS: We report on our prospectively collected experience during 15 years of treating 200 patients with localized bladder cancer using this regimen of 3 courses of intra-arterial cisplatin integrated with pelvic radiotherapy and reserving cystectomy for salvage as required. We report on the efficacy in terms of complete response rate, ultimate tumor-free bladder preservation, overall survival and patterns of failure. We detail the acute and chronic toxicity observed to date. CONCLUSIONS: This strategy has resulted in a durable high complete response rate and overall tumor-free bladder preservation rate of 75% while maintaining a survival comparable to that achieved with cystectomy. These results corroborate the hypothesis that intra-arterial administration of cisplatin enhances radiosensitization during pelvic radiotherapy.

[Malignant mixed tumor].

The term "malignant mixed tumor" is usually synonymous with "carcinoma in pleomorphic adenoma," a secondary carcinoma developing in pre-existing pleomorphic adenoma. However, it sometimes indicates a group of tumors consisting of carcinoma in pleomorphic adenoma, carcinosarcoma (true malignant mixed tumor) and metastasizing benign mixed tumor, the latter 2 being the most infrequent. According to the data of the Japanese committee on TNM classification for salivary gland carcinomas, carcinoma in pleomorphic adenoma accounted for about 10% of all salivary gland carcinomas, both in the parotid and submandibular glands. The main type of carcinomas arising in pleomorphic adenoma were undifferentiated carcinoma, adenocarcinoma and squamous cell carcinoma. Crude 5- and 10-year survival rates were 54.7% and 42.7%, respectively. Invasive carcinomas and carcinomas of high grade malignancy carried worse prognoses. The treatment of choice for carcinoma in pleomorphic adenoma has consisted of en-bloc excision with wide margin. Invasive growth, facial nerve involvement, lymph node metastasis or high-grade malignant tumor are grounds for postoperative radiation therapy. The role of chemotherapy has not yet been well established.

Malignant mixed Müllerian tumors of the uterus: analysis of patterns of failure, prognostic factors, and treatment outcome.

PURPOSE: To determine the survival outcomes, prognostic factors, and patterns of failure in patients with malignant mixed Müllerian tumor (MMMT) of the uterus. METHODS AND MATERIALS: Between 1954 and 1998, 300 patients with clinical Stage I-III MMMT of the uterus were treated with curative intent at The University of Texas M. D. Anderson Cancer Center. Their hospital records were reviewed to obtain patient and tumor characteristics; details of surgery, radiotherapy (RT), and chemotherapy; and long-term outcome. Surviving patients were followed for a median of 109 months (range 15-138). Survival rates were calculated using the Kaplan-Meier method, with differences assessed by log-rank tests. RESULTS: Of the 300 patients, 113 (38%) were treated with surgery alone, 160 (53%) with surgery plus adjuvant EBRT or ICRT, and 27 (9%) with RT alone. Forty-eight patients received adjuvant chemotherapy. At 5 years, the overall rates of survival and cause-specific survival were 31% and 33%, respectively. Women who were postmenopausal or had a history of prior pelvic RT, pain at presentation, clinical Stage II-III disease, uterine enlargement (>/=12 weeks), or an abnormal Papanicolaou smear finding had a significantly poorer prognosis than the other patients in the series. Of the 273 patients who underwent surgery, those who had positive abdominal washings, uterine length >10 cm, or extrauterine spread of disease to the cervix, adnexa, or peritoneum had a significantly worse prognosis than the other patients. Factors found on multivariate analysis to have an independent adverse influence on cause-specific survival included postmenopausal status (p = 0.0007, relative risk [RR] 3.3), uterine length >10 cm (p = 0.0001, RR 2.2), cervical involvement (p = 0.002, RR 1.8), and peritoneal involvement (p = 0.0001, RR 4.3). At 5 years, the rates of pelvic and distant disease recurrence for the entire group of 300 patients were 38% and 57%, respectively. The most common site of distant recurrence was the peritoneal cavity. Patients treated with pelvic RT had a lower rate of pelvic recurrence than patients treated with surgery alone (28% vs. 48%, p = 0.0002), but the overall survival rates (36% vs. 27%, p = 0.10) and distant metastasis rates (57% vs. 54%, p = 0.96) were not significantly different. However, patients treated with pelvic RT had a longer mean time to any distant relapse (17.3 vs. 7.0 months, p = 0.001) than patients treated with surgery alone. The use of adjuvant chemotherapy did not correlate with the survival rate or rate of distant metastasis. CONCLUSION: Adjuvant pelvic RT decreased the risk of pelvic recurrence and may delay the appearance of distant metastases after hysterectomy for MMMT. However, the survival rates remain poor because of a high rate of distant recurrence. As more effective systemic chemotherapy is developed to control microscopic distant disease, the role of RT in controlling locoregional disease in the pelvis and abdomen may become more important. Future research should consider programs that integrate surgery, RT, and chemotherapy to maximize the probability of cure.

Osteosarcomatous differentiation in phyllodes tumors.

Osteosarcomatous differentiation in phyllodes tumors is uncommon. The clinicopathologic features of 22 such cases in our files were retrospectively reviewed to evaluate the prognostic significance of this rare neoplasm. All patients were women between 40 and 83 years of age (mean, 60 years). Most (73%) presented with a palpable mass. None had prior irradiation to the breast or chest region. Patients were treated with excisional biopsy (N = 4), partial mastectomy (N = 1), or mastectomy (N = 17). All axillary nodes, dissected in 11 patients, were free of tumor. Two patients had extramammary spread at diagnosis. The neoplasms measured 1.9-15 cm (mean, 6.4 cm); 54% were grossly circumscribed or multilobulated. The osteosarcomatous component was classified as fibroblastic (N = 11), osteoclastic (N = 6), or osteoblastic (N = 5) and occupied a variable percentage of the phyllodes' stroma ranging from -25% to essentially 100% of the neoplasm. Of 21 patients with available follow-up, 11 (52%) were alive at a median follow-up of 44 months. Nine patients (43%) developed locally recurrent (N = 1) or metastatic (N = 8) disease. Metastases were clinically apparent within 1 year of diagnosis in all eight patients; seven died within 12 months of detection of initial metastasis. By univariate analysis, gross tumor size and osteosarcoma subtype significantly correlated with prognosis. In a multivariate analysis, neither of these factors were independent prognosticators. Phyllodes tumors with an osteosarcomatous component are potentially aggressive neoplasms, particularly when large (>5 cm) or associated with an osteoclastic or osteoblastic osteosarcoma. Complete excision without axillary dissection is advised.

[Malignant salivary gland tumors].

Records of 60 patients with primary salivary gland tumors were retrospectively analyzed. Most were European Jews, 60% were males, and the average age was 57 years. The parotid gland was the most frequent site of origin (76%). The main presenting symptom was painless swelling. Pain or facial palsy were rare and associated with poor prognoses. The most common types were mucoepidermoid, adenocystic, adenocarcinoma and malignant, mixed carcinomas (in descending order of frequency). Squamous cell carcinoma was the most prevalent histologic type. Most patients presented at an advanced stage. Treatment was mainly surgical and postoperative radiotherapy was given to those with advanced disease. Most recurrences occurred within 3 years of initial treatment. Actuarial 10-year survival for all patients was 40%. Superior survival rates were achieved in women, probably due to less aggressive malignancies. Low grade mucoepidermoid carcinoma had a favorable prognosis, whereas anaplastic carcinoma had the worst. Other significant prognostic factors included stage and grade of disease.

Benign and malignant salivary gland-type mixed tumors of the lung. Clinicopathologic and immunohistochemical study of eight cases.

BACKGROUND: Primary lung tumors showing features of salivary gland-type neoplasms are extremely rare. METHODS: Eight patients with primary lung neoplasms showing light microscopic and immunohistochemical features of salivary gland-type mixed tumors were studied. RESULTS: The patients were six women and two men, ages 35-69 years (mean, 52.5 years). The tumors ranged from 2 to 16 cm in greatest diameter. In two patients the lesions presented as polypoid endobronchial lesions obstructing the lumen; in another two patients the lesions were found in close proximity or in continuity with a bronchus; in three patients, the lesions presented as peripheral parenchymatous nodules unrelated to a bronchus; and in one patient, the relationship to the bronchus could not be determined. Histologically, the lesions were biphasic, showing admixtures in varying proportions of epithelial elements containing a predominant myoepithelial cell population with a stromal component containing an abundant myxoid or focally chondroid matrix. Immunohistochemical studies showed strong positivity of the cells in the epithelial component with low molecular weight keratins (CAM 5.2), and to a lesser extent with broad spectrum keratin, actin, and vimentin antibodies. The cells also showed variable reactivity in the epithelial and nonepithelial elements with S-100 protein and glial fibrillary acidic protein. Six tumors were grossly and histologically benign; in two patients, the tumors were larger, locally invasive, and showed more atypical histologic features. All patients were treated with surgical excision. On follow-up, of the six patients with histologically benign-appearing tumors, one was alive and well 6 years after surgery; another died 4 years after surgery of a second unrelated malignancy; one died during the immediate postoperative period of myocardial infarction; and three have been lost to follow-up. In the two patients with histologically atypical lesions, the tumors recurred and metastasized after 2 and 3 years, respectively, with one of them leading to death caused by widespread metastases and superior vena cava syndrome. CONCLUSIONS: Review of the literature and the findings in the current series indicate that salivary gland-type mixed tumors of the lung may present with a spectrum of histologic features and clinical behavior, ranging from benign to frankly malignant, similar to that observed for their salivary gland counterparts. Size of the lesion at the time of presentation, extent of local infiltration, and degree of mitotic activity appear to be the most reliable prognostic features of these tumors.

[Primary malignant tumours in submandibular region].

From 1959 and 1989, 65 patients with primary malignant tumour of submandibular region, including 18 cases of adenoid cystic carcinoma, 16 cases of malignant mixed tumour, 14 cases of adenoid carcinoma, 10 cases of undiferentiated carcinoma and 7 cases of squamous cell carcinoma, were treated at this hospital by surgery or combined therapy. The 3- and 5-year survivals were 60% and 42.9%, respectively. Those of malignant mixed tumours were somewhat better, being 75% and 61.5%. Submandibular gland excision or regional/elective dissection was used if the tumours were local and no capsule invasion. Particular attention was given to the identification of perineural invasion, softtisure extension, bone invasion and lymph node metastasis. Wide excision and neck dissection were necessary for above mentioned pathological changes. Combined therapy was important for those patients with positive margin, recurrence, low- or un-differentiation and advanced stage. The main factors affecting survival were local-regional failure.

Cisplatin, vinblastine and bleocin in the treatment of disseminated testicular cancer.

Fifty-nine stage IV disseminated testicular cancer patients underwent 5 or more courses of cisplatin, vinblastine and bleocin (PVB) chemotherapy from August 1981 to July 1989. Tumour histology included 15 seminomas, 13 embryonal carcinomas, 13 teratocarcinomas and 18 mixed tumours. Thirty-four patients (58%) achieved complete remission with an average duration of 56+ months (range 3 to 113+), and 12 patients (20%) achieved partial remission with an average duration of 8.5 months (range 2 to 33). The overall response rate was 78%. Four patients achieved complete remission after adjunctive surgery. The best response was obtained in seminoma patients (73% complete remission). The 5-year survival is 88% for complete responders, 10% for partial responders, and 53% overall. The PVB combination has considerably improved the survival of disseminated testicular cancer patients, but the low survival rate in poor-risk patients necessitates more aggressive chemotherapy regimens.