Extranodal diffuse large B-cell lymphoma presenting with extensive organ involvement.

Extranodal involvement in diffuse large B-cell lymphoma (DLBCL) is defined as disease outside of the lymph nodes and occurs in up to one-third of patients, though multiorgan extranodal involvement is rare. Here, we describe a case of a patient presenting with widely metastatic lesions, including involvement of the lung, parotid gland, breast, pancreas, femur and multiple soft tissue masses, with initial concern for primary breast malignancy. Breast pathology and imaging were consistent with triple-expressor, double-hit stage IV high-grade B-cell lymphoma with extensive extranodal involvement. Extranodal involvement is a poor prognostic factor associated with high rates of treatment failure, and novel therapies targeting CD19 are currently being studied for relapsed and refractory DLBCL. Extranodal disease is a complex entity that can involve virtually any organ system and should be considered for new presentations of malignancy.

Metastases to the parotid glands: An institutional experience.

BACKGROUND: Metastatic lesions to the salivary gland are rare and mostly affect the parotids. Metastases represent 8% of all malignant lesions of the parotid gland. Around 80% originate from squamous cell carcinomas (SCC) of the head and neck region. Fine needle aspiration (FNA) plays a crucial role in distinguishing primary salivary gland lesions from metastases. Herein we describe our series of metastases to the parotid glands. MATERIALS AND METHODS: We analysed 630 parotid gland FNAs over a decade including conventional and liquid-based cytology specimens. Ancillary techniques such as immunocytochemistry (ICC) were conducted on cell blocks. RESULTS: Eighty (12.4%) cases were malignant lesions, of which 53 (63.75%) were metastases including 24% melanoma, 22.6% SCC, 19% renal carcinomas, 7.5% breast carcinomas, 11.3% lung, 9% intestinal and 1.8% testicular, malignant solitary fibrous tumour and Merkel cell carcinoma. The 53 cases, classified according to the Milan system for salivary cytopathology, belonged to 5 Suspicious for malignancy (SFM) and 48 malignant (M) categories. Forty had a known history of primary malignancy (75.4%), while 13 were suspicious to be a metastatic localisation (24.5%), distributed as 5SFM (2SCC and 3Melanoma) and 8 M. A combination of clinical history, cytomorphology and ICC identified 100% of them. CONCLUSIONS: Fine needle aspiration plays a central role in the diagnostic workup of patients with metastatic lesions to their parotid glands, thereby defining the correct management. Diagnostic accuracy may be enhanced by applying ICC. Although melanoma and SCC are the most common histological types, several other malignancies may also metastasize to the parotid glands and should be kept into consideration.

[Radiation-induced parotid leiomyosarcoma]. / Léiomyosarcome parotidien en territoire irradié.

INTRODUCTION: First case of radiation-induced parotid leiomyosarcoma. ANATOMO-CLINICAL OBSERVATION: A 50-year-old woman with a history of cervical irradiation for Hodgkin's lymphoma presented with a right parotid tumefaction. Examination noted a deep adherent pretragal mass with peripheral facial palsy. A total parotidectomy with intra-operative examination and cervical curage was performed. Histopathological analysis concluded to a grade 3 parotid leiomyosarcoma according to the National Federation of Cancer Centers. Adjuvant radiotherapy was performed. After 24 months of follow-up, the patient presented bone and liver metastases without local recurrence. DISCUSSION: This is the first case of radiation-induced leiomyosarcoma and the 12th case of parotid leiomyosarcoma described in the literature. The management associates surgery with adjuvant radiotherapy. Follow-up is by clinical examination, parotid MRI, and annual thoracoabdominal CT scan to search for metastases. Recurrences occur during the first year in 40 to 64% of cases, and distant metastases in 40 to 60% of cases. The 5-year survival rate is between 10 and 30%.

Neck management in cutaneous squamous cell carcinoma with parotid metastasis.

OBJECTIVE: Our objective is to assess the oncologic outcomes of observation, elective neck dissection (END), and elective neck irradiation (ENI) in the neck management of head and neck cutaneous squamous cell carcinoma (HNcSCC) with parotid metastasis (P+) and to evaluate the quality of life (QoL) of patients who received END or ENI. METHODS: Patients with P+ HNcSCC were retrospectively enrolled. The impact of observation, END, and ENI on regional control (RC) and overall survival (OS) was analyzed using Cox proportional hazards model with presentation via hazard ratio (HR) with a 95% confidence interval (CI). QoL was evaluated using the University of Washington Quality of Life questionnaire. RESULTS: A total of 134 patients were included in our analysis. In the Cox model for RC, both END and ENI had decreased HRs of 0.27 (95% CI: 0.15-0.69) and 0.34 (95% CI: 0.18-0.86), respectively, in comparison with observation. In the Cox model for OS, both END (p = 0.001, HR: 0.22, 95% CI: 0.10-0.72) and ENI (p = 0.006, HR: 0.30, 95% CI: 0.17-0.83) were superior to observation. In patients with three or more positive parotid lymph nodes, END resulted in significantly better RC (p < 0.001) and OS (p = 0.001) compared with ENI. The two groups were found to be comparable in all 12 domains of the University of Washington Quality of Life questionnaire. CONCLUSION: In the neck management of P+ HNcSCC, observation is not recommended. END is the preferred option, but ENI is an alternative method without compromise to survival or QoL, except in cases with three or more metastatic parotid lymph nodes.

Parotid Gland Metastases of Cutaneous Squamous Cell Carcinoma of the Head: Occult Metastases Occurrence and Their Late Manifestation.

Cutaneous squamous cell carcinomas (cSCC) are malignant tumours with excellent prognosis unless nodal metastases develop. The aim of our study is to determine the prognostic significance of the clinical stage of parotid gland metastases and the incidence of occult cervical lymph node involvement in cSCC of the head. Our retrospective analysis includes 39 patients with cSCC parotid gland metastases, 15 of whom had concurrent cervical node involvement. In 32 patients, the lymph nodes manifested at stage N3b. A total of 26 patients were treated with parotidectomy, 9 patients received radiotherapy alone, and 4 received symptomatic therapy. The surgical treatment included either total conservative (21 cases) or superficial parotidectomy (5 cases) and neck dissection (therapeutic neck dissections in 11 cases and elective in 14 cases). In all cases, surgery was performed with sufficient tumour-free resection margins. Adjuvant radiotherapy was administered postoperatively in 16 patients. Occult metastases were present in 21% of cases after an elective neck dissection, but not in any case in the deep lobe of the parotid gland. The five-year overall survival and recurrence-free interval were 52% and 55%, respectively. Patients with the cN3b stage and G3 histological grade tend to have a worse prognosis, but not at a statistically significant level. The prognosis was not worse in patients with concurrent parotid and cervical metastases compared to those with metastases limited to the parotid gland only. The addition of adjuvant irradiation, in comparison to a single modality surgical treatment, was the only statistically significant prognostic factor that reduced the risk of death from this diagnosis (p=0.013). The extent of parotidectomy (partial vs. total) had no impact on either the risk of recurrence or patient prognosis. The combination of surgery with irradiation provides the best results and should be applied to all patients who tolerate the treatment. A partial superficial parotidectomy should be sufficient, with a minimum risk of occult metastasis in the deep lobe. Conversely, the relatively high incidence of occult neck metastases indicates that patients could likely benefit from elective neck dissection.

Results of surgical treatment of lymph node metastases in patients with cutaneous squamous cell carcinoma of the head and neck.

INTRODUCTION: Out of all cutaneous squamous cell carcinomas originating in the head and neck (HNCSCC), 2-4% are associated with parotid or cervical lymph node metastasis. The aim of this study is to analyse the prognostic factors of patients with HNCSCC with lymph node involvement treated surgically. Additionally, we aim to compare the prognostic capacity of the classification of these patients according to the 8th edition of the TNM, and an alternative classification proposed by O'Brien et al. PATIENTS AND METHODS: Retrospective review of 65 patients with HNCSCC with lymph node metastasis treated surgically during the period 2000-2020. RESULTS: During the study period we carried out 13 neck dissections and 52 parotidectomies + neck dissection in patients with lymph node metastases from a HNCSCC. The great majority of patients (89.2%) received post-operative radiotherapy. The 5 year disease-specific survival was 69.9%, and the overall survival it was 42.8%. The classification proposed by O'Brien et al., based on the parotid or cervical location of the lymph node metastases, and the size and number of the metastatic lymph nodes, had a better prognostic capacity than the TNM classification. CONCLUSIONS: The surgical treatment of lymph node metastases in patients with HNCSCC achieved a high disease control. The classification based on the location, size and number of lymph node metastases proposed by O'Brien et al had better prognostic capacity than the TNM classification.

Topography and probability diagram of cervical and intra-parotid lymph node metastasis in parotid gland cancer.

In parotid gland cancer (PGC), cervical lymph node metastasis (LNM) and intra-parotid LNM are known as significant indicators of poor prognosis. However, the topography of LNM in the affected parotid gland and the lymphatic progression of PGC has never been explored in detail. This was a retrospective analysis of data from 423 patients with previously untreated primary PGC (2005 to 2020), excluding patients with squamous cell carcinoma, lymphoma or metastatic disease in the parotid gland. The pattern of LNM was analyzed by neck sub-level and parotid sub-site. Using the conditional probability of neck level involvement, a probability diagram was plotted on several thresholds to visualize the sequential progression of LNM in PGC. The pattern of LNM progression was found to be similar between low- and high-grade pathology, but the incidence differed significantly (8.0% vs. 45.4%). Intra-parotid LNs and level IIa LNs were the most common sites (57.3% and 61.0%) of LNM in PGC, followed by level III (31.7%), Ib (25.6%), IV (22.0%), IIb (20.7%) and Va (20.7%) LNM. In intra-parotid LNs, the incidence of LNM in the deep parotid LNs was relatively low (9.4%); most intra-parotid LNMs were observed in the superficial parotid (90.6%) and peri-tumoral (in contact with the tumor) (31.3%) LNs. LNM to levels Ia, Vb and contra-lateral LNM occurred only in the very late stage. Our results provide detailed information about LNM progression in PGC at the sub-level and can help clinicians decide the treatment extent, including surgery or radiation.

Metastatic parotid gland malignancy: A preliminary study in an eastern Chinese population.

OBJECTIVE: This study aimed to determine the incidence and clinicopathological patterns of metastatic carcinoma of the parotid gland. METHOD: Ninety patients with parotid gland metastases admitted to our hospital between January 2003 and December 2018 were included in this study. Clinical and pathological data were obtained from the medical records and follow-ups. Kaplan-Meier analysis was used to assess overall survival of patients. RESULTS: Among the 90 patients, parotid gland metastases originated from the head and neck in 86 (95.6%), from non-head and neck in 4 (4.4%), from the oral cavity in 30(33.3%), and from the eyelid in 21 (23.3%). Among the 85 cases with parotid gland lymph node metastasis, 45 (52.9%) were diagnosed with extra-lymph node metastasis. The capsule of the parotid lymph nodes was thinner than that of the cervical lymph nodes (P < 0.05). Hematogenous metastases to the parotid gland (only five cases) were rare, mainly from the non-head and neck malignancies. Patients with oral squamous cell carcinoma and meibomian adenocarcinoma with parotid metastatic disease had poorer overall survival (P < 0.05). CONCLUSION: Eastern China population analysis showed that parotid gland metastases usually arise from oral squamous cell carcinoma and eyelid, but rarely from cutaneous squamous cell carcinoma. Most cases metastasize to the parotid lymph nodes via the lymphatic system and are prone to extranodal extension with little or no facial nerve involvement. These findings have important implications for the treatment of metastatic parotid malignancies.

[Case of Tongue Cancer That Was Considered to Be a Metachronous Double Cancer with Parotid Gland Cancer].

In Japan, the incidence of double cancers is increasing due to the rise in cancer prevalence in the super-aging society, and the frequency is particularly high among patients with head and neck cancer. To the best of our knowledge, there has been only 1 reported case of metachronous double cancer with parotid gland cancer and tongue squamous cell carcinoma, and herein we report the outline of this case. The patient was a 70-year-old male with a smoking history. In 2017, a total parotidectomy and neck dissection for adenocarcinoma of the right parotid gland were performed at the otolaryngology department, followed by concurrent chemoradiotherapy as postoperative therapy. Pathological examination revealed adenocarcinoma NOS(pT4aN2bM0, Stage ⅣA). There was no recurrence or metastasis, and the patient was recovering well. However, in October 2022, the patient presented to the hospital with a chief complaint of pain at the right margin of the tongue. At the initial consultation, an ulcerative lesion with a slightly unclear boundary and maximum diameter of approximately 15 mm was observed on the right margin of the tongue. Since epithelialization was observed in some regions, it was diagnosed as intractable stomatitis and the patient was put under observation for the time being. With no signs of healing during the follow- up examination a month later and considering the possibility of malignant tumors, a total excision of tongue lesion was performed. Pathological examination revealed well-differentiated squamous cell carcinoma(pT1N0M0, Stage Ⅰ). Going forward, we plan to conduct careful follow-up observations with the possibility of further metachronous double cancer occurrences in mind.

Glandular metastases from renal cell carcinoma show poor clinical responses to immune checkpoint inhibition but durable responses to angiogenesis inhibitors.

While half of the metastatic clear cell renal cell carcinomas (ccRCCs) involve the lungs, metastatic lesions have been described in various other organs, including glandular tissues such as the pancreas. Recent evidence suggests that ccRCC lesions affecting the pancreas are poorly responsive to immune checkpoint inhibition (ICI) but show superior responses to tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) signalling pathway. However, this has yet to be explored in ccRCC spreading to other glandular tissues. Here we present two cases of ccRCC with glandular metastases, the first to the pancreas and the second to the parotid gland. In both patients, ICI-based immunotherapy offered minimal clinical benefit, but both had durable responses to angiogenesis inhibitors. Given the anatomic similarity between the pancreas and parotid glands, ccRCC with involvement of the parotid gland may also benefit from VEGF-targeting TKIs as opposed to ICIs.

Pembrolizumab-associated pyoderma gangrenosum in a patient with metastatic squamous cell carcinoma.

Pyoderma gangrenosum (PG) is a rare, ulcerative neutrophilic dermatosis that has been reported in association with certain medications. Recognition of medications that trigger PG may help to better understand the pathogenesis of the condition and to provide earlier diagnosis and treatment for affected patients. Herein, we report a case of new-onset PG following initiation of the checkpoint inhibitor pembrolizumab for the treatment of metastatic cutaneous squamous cell carcinoma. Our case was resistant to intralesional corticosteroid therapy, but ultimately improved with systemic corticosteroids and cessation of pembrolizumab.

Therapeutic neck dissection in head and neck melanoma patients: Comparing extent of surgery and clinical outcome in two cohorts.

BACKGROUND: The extent of surgical management of regional lymph nodes in the treatment of cutaneous head and neck melanoma on and anterior to O'Brien's watershed line is controversial. By comparing patients' cohorts of two separate melanoma expert centers we investigate the effectiveness of comprehensive versus (super-) selective neck dissection approach. METHODS: Sixty patients with macroscopic (palpable) neck node metastases (N2b) from anterior scalp and face melanoma were retrospectively studied. Forty therapeutic modified radical neck dissections (MRND; levels I-V) combined with elective parotidectomy from The Netherlands Cancer Institute (NCI) were compared with 16 (super-) selective neck dissections [(S)SND; 3-4 levels] and 4 solely MRNDs from Erasmus Medical Center (EMC). Cohorts were analyzed for site of recurrence, overall survival (OS), melanoma-specific survival (MSS), and disease-free survival (DFS). RESULTS: Clinical characteristics of patients were equal in both groups. In the NCI cohort 62.5% (n = 25) of patients recurred versus 65% (n = 13) in the EMC cohort. None of the NCI recurrences affected the parotid gland in contrast to 3 patients in the EMC group. Survival characteristics were not different between the two groups: OS (p = 0.56), MSS (p = 0.98), DFS (p = 0.92). CONCLUSION: This study does not support to continue the practice of routine elective parotidectomy and MRND in melanoma patients undergoing a lymph node dissection for macroscopic (palpable) nodal disease and justifies (S)SND.

Aggressive parotid gland and neck metastasis caused by cutaneous squamous cell carcinoma of the scalp: a case report / Metástasis agresiva de glándula parótida y cuello causada por carcinoma cutáneo de células escamosas decuero cabelludo: reporte de un caso

Introduction: The head and neck are frequent sites for the development of cutaneous cancer and squamous cell carcinoma of the skin (SCC), one of the more frequent malignant non-melanoma skin neoplasms in Chile (436 per 100,000 inhabitants). Between 5-10% skin SCC progresses aggressively generating metastasis to parotid and cervical lymph nodes. Case Report: A 82 years old male, presents painful increased volume lesion in the mandibular area. He has a history of chronic arterial hypertension, acute renal failure, SCC of the scalp, extra-pulmonary tuberculosis, chronic sun exposure and smoking. Extraoral examination showed a 4 cm lesion in the posterior third of the mandibular branch, with undefined edges, a firm consistency and painful on palpation. Intraorally, erythematous mucosa is observed, as well as lack of lubrication, tenderness and cortical bone expansion. Incisional biopsy is performed, imaging and histological exams are requested. The results indicate the presence of SCC, and therefore referral to secondary care. Many risk factors are associated with SCC development, with ultraviolet radiation the most relevant in this case, favoring its appearance on the scalp. The probability of metastasis is low, but when it happens, the majority of cases that started in the scalp, disseminate to the parotid and cervical region. Conclusion: The SCC has a good prognosis. However, there are antecedents, such as size and location, that must alert the professional to perform the monitoring, early screening, control of metastatic nodes in maxillofacial area.

Introducción: La cabeza y el cuello son sitios frecuentes de desarrollo de cáncer cutáneo y el carcinoma epidermoide de piel (CEC) es una de las neoplasias malignas sin melanoma más frecuentes en Chile (436 por 100.000 habitantes). Entre el 5% y el 10% del CCE cutáneo progresa de forma agresiva y genera metástasis en los ganglios linfáticos parótidos y cervicales. Reporte de Caso: Varón de 82 años, presenta lesión dolorosa de aumento de volumen en zona mandibular. Tiene antecedentes de hipertensión arterial crónica, insuficiencia renal aguda, CCE del cuero cabelludo, tuberculosis extrapulmonar, exposición crónica al sol y tabaquismo. El examen extraoral mostró una lesión de 4 cm en el tercio posterior de la rama mandibular, con bordes indefinidos, consistencia firme y dolorosa a la palpación. Intraoralmente se observa mucosa eritematosa, así como falta de lubricación, dolor a la palpación y expansión del hueso cortical. Se realiza biopsia incisional, se solicitan exámenes de imagen e histológicos. Los resultados indican la presencia de CCE y, por tanto, derivación a atención secundaria. Son muchos los factores de riesgo asociados al desarrollo de CEC, siendo la radiación ultravioleta la más relevante en este caso, favoreciendo su aparición en el cuero cabelludo. La probabilidad de metástasis es baja, pero cuando ocurre, la mayoría de los casos que comenzaron en el cuero cabelludo se diseminan a la región parotídea y cervical. Conclusión: El SCC tiene un buen pronóstico. Sin embargo, existen antecedentes, como tamaño y ubicación, que deben alertar al profesional para realizar el seguimiento, cribado precoz, control de ganglios metastásicos en zona maxilofacial.

Metastases of Cutaneous Squamous Cell Carcinoma Seem to be the Most Frequent Malignancies in the Parotid Gland: A Hospital-Based Study From a Salivary Gland Center.

Malignant parotid tumors account for approximately 20% of all parotid lesions. In addition to the various primary parotid lesions there are secondary parotid malignancies, such as metastases or lymphomas. Data on histopathological distribution of all malignancies-including secondary parotid lesions-is limited. Recent evidence indicated a rising surgical incidence of secondary parotid malignancies. This study aims to review the distribution of malignancies in parotid resections from a salivary gland center. A retrospective review of prospectively collected data for all patients who had received parotidectomy between 2014 and 2019 was performed. Histopathological distribution was displayed separately for all parotid malignancies and for primary parotid malignancies. Further, patients` characteristics were compared between benign and malignant parotid lesions and between the two most common malignant parotid lesions. Out of 777 patients, 614 (78.9%) patients had a benign and 164 (21.1%) patients had a malignant parotid lesion. The most common parotid malignancy was metastatic cutaneous squamous cell carcinoma (cSCC) accounting for 35.4% of all parotid malignancies. 71.5% of all malignant lesions were secondary malignancies. Patients with metastatic cSCC were significantly older (p < 0.001) and significantly more likely to be male (p < 0.001) than patients with primary parotid malignancies. No significant difference was found when the lesion size of metastatic cSCC was compared to primary parotid malignancies (p = 0.216). The present study shows the high prevalence of secondary parotid malignancies in patients who had received parotidectomy. Furthermore, it confirms a rising surgical incidence of metastatic cSCC to the parotid gland in a series from a salivary gland center. At this time, parotid surgery for malignant lesions is more likely to be performed for metastases than for primary parotid malignancies.

[Ductal carcinomas of the parotid gland]. / Les carcinomes canalaires de la parotide.

PURPOSE: To describe the clinical, therapeutic and prognostic features of ductal carcinomas of the parotid gland. MATERIAL AND METHODS: Five patients with ductal carcinoma of the parotid gland (primary and secondary carcinoma) treated, between 2007 and 2019, in our ENT department, were reviewed. RESULTS: Four men and one woman were included. The mean age was 61,4 years. One patient had a history of an invasive ductal carcinoma of the breast. Four patients consulted for swelling in the parotid region. One patient referred to our department for dysfunction of facial nerve. Skin invasion was found in one case. Four patients underwent total parotidectomy with sacrifice of the facial nerve (three cases). One patient underwent extended parotidectomy involving the skin. An ipsilateral selective neck dissection was performed in four cases. One patient had a parotid gland biopsy. Ductal carcinoma was primary in four cases and metastatic from breast origin in one case. Four patients were treated with postoperative radiotherapy. Remission was obtained in three cases. One patient had a local and meningeal recurrence. The patient with metastatic carcinoma had pulmonary, bone, hepatic and brain progression. CONCLUSION: Ductal carcinoma is a rare and aggressive tumor of the parotid gland. It can be primary or secondary. The treatment is based on surgery and radiotherapy. The prognosis is poor.