Pregnancy and delivery in an advanced cancer survivor with immune checkpoint inhibitor-induced type 1 diabetes: a case report.

PURPOSE: Given the rarity and elderly onset of immune checkpoint inhibitor (ICI)-induced type 1 diabetes (ICI-T1DM), cases leading to delivery are rare. METHOD: To our knowledge, this is the first case report of childbirth in a patient with ICI-T1DM after cancer survival. A 32-year-old woman was started on Nivolumab for metastatic parotid cancers one year after total parotidectomy. RESULT: The patient developed ICI-T1DM after 43 cycles and started multiple daily insulin therapy and self-monitoring of blood glucose. Complete response was maintained for 2 years by nivolumab, and she finished nivolumab in 77 cycles to attempt pregnancy. During the follow-up period, she began using a sensor-augmented pump (SAP). She had undetectable serum and urinary C-peptide when she started SAP. Her HbA1c level decreased from 7.8 to 6.6% without increasing hypoglycemia in one year. The patient remained in complete response after ICI discontinuation, and embryo transfer was initiated. Pregnancy was confirmed after a second embryo transfer (21 months after ICI discontinuation). At 36 weeks and 6 days, an emergency cesarean section was performed due to the onset of preeclampsia. The baby had hypospadias and bifid scrotum but no other complications or neonatal intensive care unit admission. CONCLUSION: Because ICI discontinuation and ICI-T1DM carry risks for the patient and child, the decision regarding pregnancy warrants careful consideration. Diabetologists should collaborate with patients and other clinical departments to develop a treatment plan for childbirth.

A Case of Recurrent Metastatic Parotid Acinic Cell Carcinoma Responsive to Pembrolizumab.

BACKGROUND: No clear chemotherapy regimen for recurrent or metastatic parotid cancer exists. We describe our experience with pembrolizumab to treat recurrent or metastatic parotid cancer. CASE REPORT: A 73-year-old woman with swelling in the lower part of the right ear for 10 years before surgery was diagnosed with right parotid cancer, underwent total right parotidectomy, and reported recurrence. She requested treatment due to diminished quality of life caused by neurological symptoms. Tissue was collected from the recurrent lesion and its combined positive score was >20; pembrolizumab was started 9 years postoperatively. RESULTS: To date, the patient has received 14 cycles of pembrolizumab. Evaluation by computed tomography showed a partial response to treatment. The only immune-related adverse event was grade 1 pneumonia in both lungs. CONCLUSION: Significant response to pembrolizumab in recurrent or metastatic parotid cancer is rarely reported, making this a remarkable case. We plan to continue pembrolizumab administration.

Primary T-Cell Lymphoma of the Parotid Gland.

Primary malignant lymphomas of parotid gland are very rare. Most are B-cell lymphomas, and T-cell lymphomas are very rare. Unfortunately, fine needle aspiration biopsy is non-diagnostic. We, herein, present a case of a 51-year male, who presented with a large mass in the left parotid gland that had rapidly grown over a few months. As fine needle aspiration biopsy was non-diagnostic, we decided to take an incisional biopsy to disclose the pathology. The lesion was diagnosed as T-cell lymphoma after immunohistochemical examination of the specimens. Following 2-[18F] fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT), the disease was staged as 'Stage I'. The patient received six sessions of cyclophosphamide, doxorubicin, vincristine and prednisone protocol as chemotherapy management. After the completion of chemotherapy, complete remission was achieved. In suspected cases, an incisional open parotid core biopsy should be considered for a definite diagnosis. As the treatment of lymphomas is not surgical, this approach avoids a parotidectomy, which in turn, avoids facial nerve complications. Key Words: T-cell lymphoma, Parotid gland, Malignant lymphoma, Incisional biopsy, Fine needle aspiration biopsy.

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.

Evaluating the Clinical Outcomes of Parotid Hemangiomas in the Pediatric Patient Population.

INTRODUCTION: Infantile hemangiomas (IHs) are the most common tumor of the parotid gland in children; however, there is no standard protocol for the treatment of IH. The generally accepted practice is to begin the patient on ß-blocker therapy if there are no contraindications. OBJECTIVE: The purpose of this study is to better understand the challenges and successes of management of pediatric patients with parotid IH. METHODS: This retrospective study analyzed 15 patients diagnosed with parotid IH from 2009 to 2016 who were cared for at a tertiary care center. Demographic information, lesion characteristics, and treatment course were obtained through patient chart review. RESULTS: Fifteen pediatric patients with parotid IH were evaluated. The female:male ratio was 4:1; the average age of diagnosis was 8.75 months. Most lesions were greater than 3 cm in their widest dimension (73.3%), and 13 patients underwent imaging to further clarify the parotid mass in their clinical workup. Fourteen patients began treatment with propranolol; 10 patients saw complete resolution of their IH (66.7%) and 3 had a partial response to ß-blocker therapy (20%). After discontinuation of propranolol, 2 patients had regrowth 2 to 3 months later after regression and were restarted on therapy. The average duration of treatment was 9.9 ± 8.45 months. The known adverse effects of propranolol-hypoglycemia, hypotension, bradycardia, and bronchospasm-were not observed in any patient. CONCLUSION: In the treatment of parotid IH, propranolol is the generally accepted first-line therapy, as compared to corticosteroid or interferon α injections of years past. Parotid hemangiomas, however, have a lower response rate to propranolol and a similar recurrence rate compared to IH at other sites. The treatment duration necessary tends to be longer. Future studies will aim at identifying and evaluating potential predictors of outcomes to help inform the management of parotid hemangiomas.

Case report: simultaneous occurrence of multiple myeloma and non-Hodgkin lymphoma treated by CAR T therapy.

RATIONALE: B cell lymphoma can co-occur with multiple myeloma (MM), and the prognosis in this case is usually poor. We propose the combination of CD19-chimeric antigen receptor (CAR) T cells and BCMA-CAR T cells for the treatment of such patients to obtain a superior prognosis. PATIENT CONCERNS: We present a 50-year-old patient with previous B cell lymphoma and subsequent multiple myeloma (MM). DIAGNOSIS: A diagnosis of B cell lymphoma and MM was made. INTERVENTIONS: The patient was treated with a combination of haploidentical CD19-chimeric antigen receptor (CAR) T cells and BCMA-CAR T cells. OUTCOMES: After CAR T cell therapy, the monoclonal plasma cells in the bone marrow and M protein disappeared. LESSONS: The combination therapy of CD19- and BCMA-CAR T cells is an effective measure to treat patients with concomitant or borderline cases of B cell lymphoma and MM.

Simultaneous development of Graves' disease and type 1 diabetes during anti-programmed cell death-1 therapy: A case report.

We present the first case of simultaneous development of Graves' disease and type 1 diabetes during anti-programmed cell death 1 therapy. A 48-year-old man with parotid gland adenocarcinoma and lung metastasis had received five courses of nivolumab. Fourteen days after administration of the sixth course, his casual plasma glucose and hemoglobin A1c levels were 379 mg/dL and 7.2%, respectively. Furthermore, thyrotoxicosis was detected with a blood test. Serum total ketone body and thyroid-stimulating hormone receptor antibody levels increased, and serum C-peptide level decreased to 0.01 ng/mL thereafter. Thus, we concluded that he simultaneously developed anti-programmed cell death 1 therapy-associated type 1 diabetes and Graves' disease. Among Japanese patients with autoimmune polyglandular syndrome type III, the frequency of human leukocyte antigen-DRB1*04:05 is higher in those with both type 1 diabetes and Graves' disease. Our case had human leukocyte antigen-DRB1*04:05, which might be associated with the simultaneous development of the two diseases.

Periorbital dermatitis in patients receiving docetaxel in combination chemotherapy.

Recognition of new cutaneous side effects of combination chemotherapy can help prevent unnecessary cessation or reduction of cancer therapy. Periorbital rash has not been found with docetaxel alone, but here, we report it as a result of combination chemotherapy. A series of three patients who received docetaxel in combination with other chemotherapies developed clinically near-identical, distinctive periorbital rashes. Rashes resolved by resolving underlying docetaxel-induced epiphora in conjunction with ophthalmological consultation, topical skin-directed care, and in some cases, chemotherapy dose reduction. It is important for dermatologists and oncologists to recognise the increased severity of cutaneous reactions when docetaxel is used in combination chemotherapy.

18F-FDG PET/CT for staging and response assessment of primary parotid MALT lymphoma with multiple sites involvement: A case report.

RATIONALE: Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal low-grade B cell lymphoma that generally exhibits an indolent clinical course. Currently, the application of F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in MALT lymphoma is still controversial. Herein, we reported a case of using F-FDG PET/CT for staging and response assessment of primary parotid MALT lymphoma with multiple sites involvement. As far as we know, there are no similar case reports have been published before. PATIENT CONCERNS: A 71-year-old woman, who received mass resection twice during the past 2 years due to the repeatedly relapse of facial painless masses and diagnosed as reactive lymphoid hyperplasia by pathologic tests. However, the pathological diagnosis was then changed to primary parotid MALT lymphoma after left parotidectomy operation because of a new mass found in her left parotid. Four months later, the right eyelid of the patient swelled with a blurred vision. Then, F-FDG PET/CT scan was performed for staging, and the imaging results showed an abnormal increase of F-FDG uptake in multiple sites including bilateral ocular adnexal, lungs, pleura, occipital subcutaneous tissue, left kidney, and lymph nodes. DIAGNOSES: The patient was diagnosed as primary parotid MALT lymphoma with Ann Arbor stage of IVA based on the F-FDG PET/CT findings. INTERVENTIONS: The patient received 4 cycles of chemotherapy, followed by a partial metabolic remission (PMR), which was determined by interim F-FDG PET/CT, and finally additional 2 cycles of chemotherapy. OUTCOMES: The follow-up study illustrated that the patient had been alive and doing well at 12 months after chemotherapy. LESSONS: Although MALT lymphoma normally localizes in the primary organs, the involvement of multiple organs and lymph nodes is possible. The use of PET/CT demonstrated significant clinical values in the accurate staging and response assessment of F-FDG-avid MALT lymphoma. It is potentially useful for indicating the progress and transformation of MALT lymphoma, and guidance in localization of pathological biopsy. It is also helpful for clinicians to choose reasonable treatment strategy and improve the prognosis of patients.

Marked responses to pemetrexed chemotherapy for metastatic adenocarcinoma of the parotid gland: Case series.

BACKGROUND: There are no proven systemic therapies for metastatic adenocarcinoma of the salivary glands. Pemetrexed use in adenocarcinoma of the salivary glands has not been previously described. METHODS: Retrospective case reports and literature review. RESULTS: Two patients with metastatic salivary gland adenocarcinoma were treated with single-agent pemetrexed with marked response and clinical benefit. Case 1 describes a sustained clinical response for 8 months after failing several lines of chemotherapy. Case 2 describes a marked interval response of diffuse metastatic disease at 2 months with resolution of bone pain and sustained response at 8 months. CONCLUSION: To our knowledge, this is the first report of efficacy of single-agent pemetrexed for metastatic salivary gland adenocarcinoma. Given the significant and sustained responses in heavily pretreated patients, further investigation of pemetrexed for salivary cancer may be warranted.

Acinic cell carcinoma of parotid gland with cavernous sinus metastasis: A case report.

Acinic cell carcinoma (AciCC) is a low-grade malignancy which rarely metastasizes to bone or cavernous sinuses. A 62-year-old male patient, previously treated for AciCC of right parotid with surgery and local radiotherapy, presented 10 years later with progressive visual impairment and restriction of ocular movements. Magnetic resonance imaging of the head and orbit showed an expansile lobulated mass with heterogeneous signal intensity in bilateral cavernous sinus with encasement of the internal carotid artery on both sides. Fluorodeoxyglucose positron emission tomography/computed tomography showed multiple lytic lesions with increased uptake in the left clavicle (with soft tissue component), sternum, multiple cervico-dorso-lumbar vertebrae, and ribs. Biopsy from the clavicular lesion showed AciCC. He was treated with palliative radiotherapy to cavernous sinuses and other metastatic site followed by palliative chemotherapy with six cycles of paclitaxel and carboplatin. He had a partial response to palliative treatment and had good symptomatic relief at 12 months of follow-up.

Recurrent parotid cavernous haemangioma in an adolescent, successfully treated with Propranolol.

INTRODUCTION: Parotid haemangiomas account for the majority of salivary gland tumours in children. This articles highlights the use of medical treatment for the treatment of parotid haemangioma. CASE SUMMARY: A 4 year old male underwent a superficial parotidectomy for a parotid mass that was found to be a a parotid haemangioma on histology. At the age of 14 years he presented again with a parotid mass. He had imaging which aided the diagnosis of a parotid haemangioma being made. He was treated with successfully propranolol over a period of 6 months. DISCUSSION: There are no clear guidelines for treatment of parotid haemangiomas. These lesions can represent a clinical challenge and optimal management is controversial. It was proposed that propranolol be used for treatment in this particular case. This is a non-invasive form of treatment with minimal side effects.

Report of a unique case of myoepithelial carcinoma of left parotid gland with metachronous bilateral cavernous sinus metastasis.

Myoepithelial carcinoma (MC) is a rare, locally aggressive malignant neoplasm of the salivary glands. Only few evidences on its metastatic behavior are available in the literature. We herein present a unique case of MC of left parotid gland which metastasized to bilateral cavernous sinuses. The patient was successfully treated with palliative radiotherapy and chemotherapy.

Parotid gland: an unusual site of breast cancer metastasis.

Parotid gland metastases from breast cancer are an extremely rare and unusual event with a limited number of cases recorded in the literature. A 71-year-old woman with a history of ductal adenocarcinoma of the left breast presented to the maxillofacial clinic with an asymptomatic swelling of the left parotid gland. The presentation occurred 21 years after she underwent treatment for recurrent breast cancer. Investigations led to the diagnosis of a breast cancer metastasis which was oestrogen receptor and progesterone receptor positive and negative. Positron emission tomography scan confirmed this as a solitary metastasis. She was treated with aromatase inhibitors and a stable clinical response was observed on follow-up. Surgical intervention was avoided with its potential complications such as facial nerve injury. Metastasis from breast cancer to the parotid gland is a very rare phenomenon. However, in a patient with previous breast cancer, it should be considered as a possible differential diagnosis.

Complete remission and long-term survival of a patient with melanoma metastases treated with high-dose fever-inducing Viscum album extract: A case report.

INTRODUCTION: Metastatic malignant cutaneous melanoma (MCM)-a highly immunogenic cancer-typically has a poor prognosis. Viscum album extracts (VAEs) have strong immune-stimulating, apoptogenic, and cytotoxic effects. CASE PRESENTATION: A 66-year-old MCM patient with newly diagnosed lymph node metastases opted for sole VAE treatment. VAEs were initially applied subcutaneously, and then later in exceptionally high, fever-inducing doses, both intravenously and intralesionally. The metastases shrunk over the following months, and after 2 years, all lesions had completely remitted (regional and hilar lymph nodes). The patient has been tumor free for 3.5 years at the time of publication (and for 5 years since initiation of intensified VAE treatment). Besides fever and flu-like symptoms, no side effects occurred. DISCUSSION: We presume that VAE triggered an increased release of tumor-associated antigens, enhanced immunologic recognition, and increased immune response against the tumor tissue and induced tumor remission.

Unexpected recalcitrant course of drug-induced erythema multiforme-like eruption and interstitial pneumonia sequentially occurring after nivolumab therapy.

Vemurafenib improves survival of melanoma patients. However, cutaneous side-effects commonly occur in them. Nivolumab and ipilimumab are monoclonal antibodies against programmed death 1 and cytotoxic T-lymphocyte-associated antigen 4, both of which regulate excessive T-cell activation. Although these agents induce antitumor immunity against melanoma, the modified immune condition may result in an unexpected adverse reaction which has not been observed previously. Herein, we report a case who manifested severe erythema multiforme-like eruption with mucosal involvement associated with vemurafenib following nivolumab. The patient also subsequently suffered from ipilimumab-induced interstitial pneumonia with refractory course. Such a case has never been reported. This case suggested that dermatologists should pay special attention to unexpected adverse events of these drugs, and carefully observe cutaneous and respiratory status of patients during the treatment of melanoma.