Efficacy of Immunotherapy Combined with Antiangiogenic Therapy in Treatment-Failure Patients with Advanced Carcinoma Ex Pleomorphic Adenoma of the Submandibular Gland: A Case Report.

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a rare malignant tumor that arises from a primary or recurrent benign pleomorphic adenoma (PA). Ca ex PA has an aggressive behavior and poor prognosis. To date, there are no standardized therapeutic methods. Herein, we reported a case of a 57-year-old Chinese female with Ca ex PA of the submandibular gland. After surgery, cervical lymph nodes recurred, and multiple distant metastases were detected. During the treatment, she received multiple chemotherapies and radiotherapy but suffered from multidrug resistance and repeated disease progression. Hence, PD-1 inhibitor (sintilimab), in combination with anlotinib, was administered, which resulted in better control of pulmonary metastases compared to the other treatment regimens. This provided an alternative treatment option for Ca ex PA of the submandibular gland patients with failed multiple therapies.

Mixed response and mechanisms of resistance to larotrectinib in metastatic carcinoma ex pleomorphic adenoma of the parotid harboring an NTRK2 fusion: A case report.

INTRODUCTION: Standardized systemic treatment options are lacking for carcinoma ex pleomorphic adenoma, which is a rare and aggressive tumor primarily found in salivary glands.Here we report the case of a 63-year-old male with carcinoma ex pleomorphic adenoma of the left parotid and parapharyngeal space harboring a neurotrophic receptor tyrosine kinase (NTRK) 2 fusion who was treated with a small molecule inhibitor that targets the tropomyosin receptor kinase (TRK) proteins. To the best of our knowledge, no similar case has been described in the literature so far. PATIENT CONCERNS: After multiple surgical resections and radiotherapy for localized cancer disease over several years, our patient again developed an increasing swelling and pain around the left ear and numbness of the left half of the face. DIAGNOSIS: Magnetic resonance imaging and positron emission tomography/computed tomography scans showed tumor recurrence in the left parotid, below the left ear, and in the parapharyngeal space, as well as metastases of the lungs and cervical lymph nodes. As data on the efficacy of systemic therapies for inoperable carcinoma ex pleomorphic adenoma are scarce, we performed a next-generation sequencing that revealed the presence of a hitherto unknown NTRK2 fusion. INTERVENTIONS: Treatment with the TRK inhibitor larotrectinib was initiated, which induced rapid symptom improvement. However, part of the tumor had to be removed shortly afterwards due to local progression. Molecular testing did not demonstrate any alterations accounting for resistance to larotrectinib, with maintenance of the NTRK2 fusion. OUTCOMES: Three months later, imaging confirmed mixed response. While the reason for this remains unknown, the patient is in good condition and continues to receive larotrectinib. CONCLUSION: It remains unclear why our patient showed mixed response to larotrectinib and further studies are needed to explore other possible mechanisms of resistance.

Significant and durable clinical benefit from trastuzumab in 2 patients with HER2-amplified salivary gland cancer and a review of the literature.

BACKGROUND: Salivary ductal carcinoma and carcinoma ex pleomorphic adenoma (CEPA) are aggressive salivary gland cancers with poor prognosis. The standard of care is resection with or without radiotherapy, and there are no established systemic therapy options. METHODS: We describe 1 patient with metastatic CEPA and 1 patient with metastatic recurrent salivary duct carcinoma whose tumors were evaluated by comprehensive genomic profiling. Testing identified human epidermal growth factor receptor 2 (HER2) amplification in both patients, and an additional activating HER2 mutation in the CEPA case. RESULTS: Both patients were treated with the HER2-targeting monoclonal antibody trastuzumab (herceptin) plus chemotherapy and experienced rapid responses. Subsequently, both patients were given single-agent maintenance trastuzumab and continue to experience durable disease control. CONCLUSION: Given the poor prognosis for salivary gland cancers and the limited treatment options upon recurrence or metastasis, patients should be tested for all classes of HER2 alterations. In cases with HER2 overexpression or activation, targeted therapies, such as trastuzumab are promising. © 2016 Wiley Periodicals, Inc. Head Neck 39: E40-E44, 2017.

Quimioterapia metronómica para adenocarcinoma pleomorfo avanzado de nasofaringe / Metronomic chemotherapy for advanced pleomorphic adenocarcinoma of the nasopharynx

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Sustained response of carcinoma ex pleomorphic adenoma treated with trastuzumab and capecitabine.

BACKGROUND: Carcinoma ex pleomorphic adenoma is a rare histologic subtype of salivary gland cancer with an overall poor prognosis. Limited histopathologic analyses have shown that some such tumors exhibit significant HER2/neu immunoreactivity, suggesting a potential role for HER2-based therapy. We report here a case of a 58-year old man with metastatic carcinoma ex pleomorphic adenoma who achieved a sustained long term response to combination therapy with trastuzumab and capecitabine. CASE PRESENTATION: A 58 year old man presented with T1N2bM0 carcinoma ex pleomorphic adenoma and underwent surgery followed by adjuvant radiation therapy. Multiple metastases to bone were documented one year later. Since the original tumor was strongly HER2/neu positive by immunohistochemistry, the patient was treated with trastuzumab, capecitabine, and zoledronic acid. He experienced total resolution of symptoms and repeat FDG-PET scan after three cycles revealed interval disease resolution. Continued treatment has resulted in maintenance of disease control for over 2 years. CONCLUSION: This case illustrates the successful long term treatment of carcinoma ex pleomorphic adenoma with targeted therapy with trastuzumab in combination with chemotherapy. In the absence of definitive clinical trials which are unlikely to be performed due to the rarity of this tumor, case reports such as this one suggest potential utility for trastuzumab in combination with chemotherapy in the treatment of HER2/neu-overexpressing carcinoma ex pleomorphic adenoma.

Carcinoma ex pleomorphic adenoma of soft palate with cavernous sinus invasion.

BACKGROUND: Carcinoma ex pleomorphic adenoma (CXPA) is an aggressive salivary gland malignancy and rare in minor salivary gland. A soft palate CXPA initially presenting as direct cavernous sinus (CS) invasion is very rare. CASE PRESENTATION: A 60-year-old male had a 3-month history of a small soft palatal mass with progressing left cheek numbness, proptosis, and disturbed vision. Biopsy of soft palatal tumor showed pleomorphic adenoma. Magnetic resonance imaging showed a tumor involving left maxilla, and extended from pterygopalatine fossa, inferior orbital fissure to CS. Excision of tumor revealed CXPA. Adjuvant concomitant chemo-radiation therapy (CCRT) was given. The tumor recurred 5 months later in left CS which was re-treated with CCRT. The disease status was stable at 2 years after the diagnosis of CXPA. CONCLUSION: We present this case to emphasize that patients with symptoms such as facial numbness, proptosis and disturbed vision should be carefully investigated for lesions invading CS by perineural spread.

[Clinical analysis of salivary malignant pleomorphic adenoma--a report of 95 cases].

BACKGROUND & OBJECTIVE: Malignant pleomorphic adenoma is rare with extensive location, which makes it difficult to evaluate the efficacy of the treatments. This study was to summarize the clinical features of salivary malignant pleomorphic adenoma, and thus to explore the treatment principle and efficacy of the treatment. METHODS: Clinical data of 95 salivary malignant pleomorphic adenoma patients, treated in Cancer Center, Sun Yat-sen University from May 1970 to Oct. 2000, were analyzed retrospectively. The overall cumulative survival rate was estimated using life table method by SPSS10.0 software. Survival curves were compared with Gehan method. RESULTS: The 5-, 10-, and 15-year overall survival rates of the 95 patients were (64.9+/-4.9)%, (56.3+/-5.4)%, and (47.8+/-6.1)%, respectively. The 5-and 10-year disease-specific survival rates for the patients received surgery (51 cases), surgery plus radiotherapy (35 cases) were 76.1%, 63.7% and 69.9%, 50.8%, respectively, but the 5-and 10-year disease-specific survival rates for the patients received radiotherapy only, chemotherapy only and radiochemotherapy (4 cases) were all 0. CONCLUSIONS: Surgery or surgery-dominated multi-modality are the principal treatment modalities for salivary malignant pleomorphic adenoma. The efficacy of surgery and surgery plus radiotherapy is better than non-surgery treatments.

Adenoma pleomórfico de septo nasal: relato de caso e revisão da literatura / Pleomorphic Adenoma of the Nasal Septum: a case Report and a Review of the Literature

Os autores descrevem um caso de adenoma pleomórfico de septo nasal em paciente do sexo masculino, com 23 anos de idade, com lesão arredondada, vermelha, implantada na mucosa septal anterior, na área de Little, obstruindo a fossa nasal direita. Foi tratado por remoção cirúrgica total, sem lesão residual ou recidivante. Este tumor é originado de glândula salivar, sendo extremamente raro na cavidade nasal.

The authors describe a case of pleomorphic adenoma of the nasal septum in a 23-year-old mate patient with a round lesion, red-coloured, fixed in the anterior septal mucosa, area of Little, obstructing the right nasal cavity. The procedure used was the complete surgical removal without residual or recurrent lesion. This tumour has its origin in the salivary glands being extremely rare in the mucosa of the nasal cavity.

Vinorelbine treatment of recurrent salivary gland carcinomas.

Twenty patients (13 males, 7 females, median age 61 years, range 27-74) with recurrent adenocarcinoma-like tumors of major (10 patients) and minor (10 patients) salivary gland origin (13 adenoid cystic carcinoma, 5 adenocarcinoma, 1 malignant mixed tumor, 1 undifferentiated carcinoma) were treated with vinorelbine at the dose of 30 mg/m2 i.v. weekly. Sixteen patients had been previously treated with surgery + radiation, 3 with surgery + radiotherapy + Novantrone and 1 with radiotherapy alone. Nine patients had local recurrence, 2 local relapse + metastasis and 9 metastasis alone. Site of metastases are: lung (7), bone (1), lung + bone (2), lung + bone + lymph-node + skin (1). Overall 174 courses were given (median 9, range 6-19). Responses were: PR in 4 patients (20%) with a median duration of 6 months (3-9), 9 NC (45%) with a median duration of 3.5 months and 7 PD (35%). The median survival time was 10 months for PR/NC patients, 4 months for non-responders. Median overall survival was 7 months. Vinorelbine has a moderate activity in these very advanced cases.

Chemotherapy for salivary gland cancer.

Because of the scarcity of such lesions, little is known about the efficacy of chemotherapy for advanced salivary gland cancers. Although surgery and irradiation are the mainstays of treatment, patients with recurrent tumors and those with unresectable or metastatic cancer are not candidates for this usual approach. Ten patients with recurrent, metastatic, or unresectable salivary gland tumors were treated with combination chemotherapy, primarily with cisplatin, doxorubicin hydrochloride (Adriamycin), and cyclophosphamide, or cisplatin with 5-fluorouracil. In patients whose tumors exhibited no response, second-line drugs were used. The overall response rate was 50%--with one complete response--but the duration of response was short. This report contributes to the growing data base that demonstrates definite chemosensitivity of these tumors. To date, 116 patients have been reviewed. Adenocarcinoma-like cancers respond best to cisplatin, doxorubicin hydrochloride, and 5-fluorouracil. High-grade mucoepidermoid carcinoma may show a sensitivity similar to that of squamous cell carcinoma. Multi-institutional protocols need to be developed to assess the roles of adjuvant and palliative chemotherapy in the treatment of salivary gland cancer.

Histopathological studies on experimental murine salivary gland tumours treated with adriamycin: evidence for an anti-myoepithelial cell action.

Mice bearing pleomorphic salivary tumours induced by polyoma virus underwent chemotherapy with Adriamycin. Animals were killed at 2 day intervals and the tumours examined histologically. Two days after a single dose of Adriamycin, gross vacuolation degeneration was seen around ductal cells at sites corresponding to myoepithelial cells. At subsequent time periods there was progressive degeneration of other tumour elements. It is proposed that myoepithelial cell death in salivary gland tumours induced by Adriamycin may be an important factor in the early response of this tumour to chemotherapy.