Prevalence of Occult Central Lymph Node Metastasis by Tumor Size in Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: While papillary thyroid carcinoma (PTC) is associated with high occult central neck metastasis (CNM) rates, prophylactic central neck dissection (pCND) is controversial. This meta-analysis aims to look at the occult CNM rate according to tumor size. METHODS: A literature search was conducted in PubMed from inception to April 2023. Inclusion criteria were primary studies that determined occult CNM rates in cN0 PTC by tumor size. Heterogeneity, influential case diagnostics, and proportion data were evaluated with Cochran's Q-test, Baujat plots and Forest plots, respectively. RESULTS: Fifty-two studies were included in this meta-analysis. The findings demonstrated an occult CNM rate of 30.3% for tumors ≤ 5 mm, 32.7% for tumors ≤ 1 cm, 46.0% for tumors between 1 and 2 cm, 43.1% for tumors between 2 and 4 cm, and 61.2% for tumors > 4 cm. The heterogeneity of each study group was high, though no publication bias was noted. While there was a trend towards increased occult CNM rates with larger tumors, comparisons between different size cutoffs varied in significance. CONCLUSION: This comprehensive review affirms that occult CNM is high and that an ipsilateral pCND can be justified in all PTC patients for accurate differentiation between Stage I and Stage II disease and its clinical implications.

Single-center prospective study on the efficacy of nivolumab against platinum-sensitive recurrent or metastatic head and neck squamous cell carcinoma.

Nivolumab, an immune checkpoint inhibitor, is beneficial to patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, platinum-sensitive R/M-HNSCC has not yet been studied. Hence, in this prospective study, we evaluated the efficacy and safety of nivolumab in patients with platinum-sensitive R/M-HNSCC. This prospective single-arm study was conducted in a single institution in Japan. Patients with platinum-sensitive R/M-HNSCC (defined as head and neck cancer that recurred or metastasized at least 6 months after platinum-based chemotherapy or chemoradiotherapy) were enrolled. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), overall response rate (ORR), immune-related adverse events (irAEs), and quality of life (QOL). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031324). Twenty-two patients with platinum-sensitive R/M-HNSCC were enrolled. The median OS was 17.4 months, and the 1-year OS rate was 73%. The median PFS was 9.6 months, 1-year PFS rate was 48%, and ORR was 36%. Sixteen irAEs were recorded in 12 patients; however, no grade 4 or 5 irAEs were observed. The QOL assessments revealed that nivolumab did not decrease the QOL of patients. Nivolumab is effective against platinum-sensitive R/M-HNSCC with acceptable safety.

Electrochemotherapy for the palliative management of non-skin-origin head and neck cancer: case series and UK national survey.

OBJECTIVES: Electrochemotherapy uses electric fields to facilitate the influx of chemotherapy into cancer cells, producing a targeted effect. For head and neck cancer, it is mainly used for palliation of non-skin-origin metastases. It is used infrequently in the UK. This paper presents our experience and a UK survey to identify its frequency of use. METHODS: Between 2016 and 2019, a prospective database was created and reviewed. Only patients with non-skin-origin metastatic head and neck cancer, with no other palliative options, were included. Survival length, complications and symptomatic benefit were assessed. The survey was conducted via e-mail. RESULTS: Five patients were included: three with squamous cell carcinoma, one with esthesioneuroblastoma and one with hepatocellular carcinoma. Survival ranged from 1 month to over 20 months. Minor complications were seen. Only 15 out of 69 UK head and neck multidisciplinary teams offer electrochemotherapy. CONCLUSION: Electrochemotherapy is a well-tolerated adjunct to standard palliation of metastatic head and neck cancer, and is offered by a limited number of UK multidisciplinary teams.

Scalp metastasis as initial presentation of neuroendocrine carcinoma.

Neuroendocrine carcinomas are a rare, heterogenous group of malignancies that arise from neuroendocrine cells throughout the body. Cutaneous metastasis of neuroendocrine carcinoma is uncommon and they can be easily misdiagnosed as benign epidermal cysts or Merkel cell carcinoma. Collectively, histopathology, immunochemical profile, biochemical markers, and nuclear imaging can guide the diagnosis of neuroendocrine metastasis and localization of primary tumors.

Systematic review and meta-analysis of cervical metastases in oral maxillary squamous cell carcinoma.

BACKGROUND: Management of the node-negative neck in oral maxillary squamous cell carcinoma (SCC), encompassing the hard palate and upper alveolar subsites of the oral cavity, is controversial, with no clear international consensus or recommendation regarding elective neck dissection in the absence of cervical metastases. AIM: To assess the occult metastatic rate in patients with clinically node negative oral maxillary SCC; both as an overall metastatic rate, and a comparison of patients managed with an elective neck dissection at index surgery, compared to excision of the primary with clinical observation of the neck. METHODS AND RESULTS: A systematic review was performed by two independent investigators for studies relating to oral maxillary SCC and analysed according to PRISMA criteria. Data were extracted from Pubmed, Ovid MEDLINE, EMBASE, and SCOPUS via relevant MeSH terms. Grey literature was searched through Google Scholar and OpenGrey. Five hundred and fifty-three articles were identified on the initial search, 483 unique articles underwent screening against eligibility criteria, and 29 studies were identified for final data extraction. Incidence of occult metastases in patients with clinically node negative oral maxillary SCC was identified either on primary elective neck dissection or on routine follow up. Meta-analyses were performed. Of 553 relevant articles identified on initial search, 29 were included for analysis. The pooled overall rate of occult metastases in patients initially presenting with clinically node-negative disease was 22.2%. There is a statistically significant effect of END on decreasing regional recurrence demonstrated in this study (RR 0.36, 95% CI 0.24, 0.59). CONCLUSION: The results of this systematic review and meta-analysis suggest elective neck dissection for patients presenting with hard palate or upper alveolar SCC, even in a clinically node negative neck.

Survival predictors and outcomes of patients with recurrent and/or metastatic head and neck cancer treated with chemotherapy plus cetuximab as first-line therapy: A real-world retrospective study.

BACKGROUND: In patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) the estimated prognosis is usually poor. Patient-specific factors that affect prognosis should be considered when choosing therapy. We conducted a retrospective, single-center analysis in patients treated with first line platinum and antiEGFR antibody-containing regimen. The objective was to generate real-world data considering treatment outcomes and to identify predictors of survival. PATIENTS/METHODS: Clinical charts of patients treated with cetuximab and platinum-based chemotherapy (CT) for R/M HNSCC in first-line setting, between January-2009 and December-2018 were assessed. In these 103 patients, the prognostic value of site of the primary tumor, age at diagnosis, gender, Cetuximab induced skin toxicity and prior treatments were studied multivariately. To evaluate progression free survival (PFS) and overall survival (OS), Kaplan-Meier curves and the log-rank test were used. The Coxregression model was used to investigate the effect of these variables on OS. RESULTS: Longer OS was associated with oral cavity tumor location (p = 0,003), European Cooperative Oncology Group-Performance Status 0 (ECOG-PS) (p = 0,01), complete/partial response (p<0,0001), cetuximab monotherapy until disease progression or unacceptable toxicity (p = 0,037) and Grade 2-4 cetuximab induced skin toxicity (p = 0,037). The median follow-up period was 11,7 months. The mortality rate was 90,3% during this retrospective cohort assessment. The PFS was 7,1 months (95% confidence interval (CI), 5,6-8.6). The OS was 11,7 months (95%CI, 10,5-12,8). CONCLUSIONS: The present study demonstrates that the combination of cetuximab with platinum-based CT was effective in R/M HNSCC. Among patients with R/M HSCC treated with platinum plus cetuximab as first-line therapy, primary site, ECOG-PS, grade 2-4 cetuximab induced toxicity, and weekly cetuximab monotherapy have a marked impact on OS.

Fascia lata packing and tension suturing for symptomatic pseudomeningocele after recurrent cervical intradural tumour resection.

In recurrent posterior cervical intradural tumour resections, serious complications can be developed. The dural can become affected by inflammatory factors or removed during tumor resection; if cerebrospinal fluid (CSF) leakage cannot be stopped by duraplasty, artificial meninges or fascia repair, large pseudomeningocele can develop posteriorly within the soft tissue of the neck. When the pressure of the CSF cannot be maintained steadily, persistent clinical symptoms can occur, such as postural headache or central fever. Moreover, the skin can also be penetrated in a few patients even after extension of the drainage duration, lumbar cistern drainage or skin suturing, leading to the induction of life-threatening intra-cranial infections. Is there a simple and effective surgical method to address this scenario? The aim of this study was, therefore, to investigate the effectiveness of fascia lata packing and tension suturing in the treatment of symptomatic pseudomeningocele after recurrent posterior cervical intradural tumour resection. In our study, nine consecutive spinal surgery patients were recruited from January 2008 to January 2018. All pseudomeningoceles were combined with postural headache, central neurological fever or wound non-union. There were 3 cases of melanocytoma, 3 cases of nasopharyngeal carcinoma metastasis, 2 cases of breast cancer metastasis, and 1 case of spinal canal lymphadenoma. Standard patient demographics, diagnosis, post-operative symptoms, wound healing time, and the largest pre- and last follow-up pseudomeningocele area on axial MRI sections were recorded. All cases were followed-up successfully, from 12 to 24 months, with an average of 15.3 months. Our observations indicate that all wounds healed successfully. The wound union time was 20.7 days on average. After wound union, these patients became symptom free. The largest cerebrospinal fluid area on axial MRI sections improved significantly from 42.9 ± 5.01 cm2 at p re-operation to 6.6 ± 1.89 cm2 at 1 year post-operation (P < 0.05); Our data indicate that .the proposed procedure is simple, safe and effective. And more importantly, it allows rapid closure of any cerebrospinal fluid leakage pools.

Pulmonary Pleomorphic Carcinoma Mimicking Primary Sarcoma of the Neck: A Case Report and Literature Review.

We describe our challenge in diagnosing an unusual and rapidly progressing case of pulmonary pleomorphic carcinoma (PPC)-a rare, poorly differentiated, or undifferentiated non-small-cell carcinoma that can metastasize locally or distantly and has a poor prognosis. Our patient was an elderly man with a one-month history of abdominal pain, anorexia, and weight loss, diagnosed with atrophic gastritis via endoscopy, and treated medically without improvement. A week later, this patient developed pain in the head, neck, and shoulder area, and further examination revealed a thickening of his left neck and shoulder, with no palpable lymph nodes. Computed tomography (CT) of the neck, chest, and abdomen led us to believe that we might be dealing with primary sarcoma of the neck since no lung mass was evident. Further investigation could not be performed because the patient's status deteriorated rapidly. An autopsy revealed that soft tissue in the left neck and the mesentery was invaded by poorly differentiated polymorphic malignant cells, which were also seen in the lung lesion. Immunohistochemically, these malignant cells were all positive for AE1/AE3, CAM5.2, TTF-1, Napsin-A, and Vimentin. The cells were also positive for programmed death-ligand 1 staining with a low level of tumor proportion score (over 1%). The final diagnosis was PPC with metastases to soft tissues in the left neck and the mesentery. A review of previous case reports of PPC revealed that soft tissue is an uncommon site for metastasis, and that our CT findings were rather unusual. We hereby present our case and review of published case reports, with the hope that an awareness of the heterogeneous features of PPC could prompt timely biopsy and histological diagnosis.

A systematic review of the primary squamous cell carcinoma of the external auditory canal: survival outcome based on T-staging and proposal of a new classification.

OBJECTIVE: This study aimed to provide a systematic review on survival outcome based on Pittsburgh T-staging for patients with primary external auditory canal squamous cell carcinoma. METHOD: This study was a systematic review in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed until January 2018; pertinent studies were screened. Quality of evidence was assessed using the grading of recommendation, assessment, development and evaluation working group system. RESULTS: Eight articles were chosen that reported on 437 patients with external auditory carcinoma. The 5-year overall survival rate was 53.0 per cent. The pooled proportion of survivors at 5 years for T1 tumours was 88.4 per cent and for T2 tumours was 88.6 per cent. For the combined population of T1 and T2 cancer patients, it was 84.5 per cent. For T3 and T4 tumours, it was 53.3 per cent and 26.8 per cent, respectively, whereas for T3 and T4 tumours combined, it was 40.4 per cent. Individual analysis of 61 patients with presence of cervical nodes showed a poor survival rate. CONCLUSION: From this review, there was not any significant difference found in the survival outcome between T1 and T2 tumours. A practical classification incorporating nodal status that accurately stratifies patients was proposed.

Multiple simple cystic metastases in the lateral neck at presentation with papillary thyroid microcarcinoma: A case report.

INTRODUCTION: Metastasis of a papillary thyroid microcarcinoma (PTMC) in the lateral neck is characterized primarily by solid lymphadenopathy, although some cases may rarely present with a cervical cystic mass. We report a case of lateral cervical lymph node metastases of PTMC that appeared as a cystic lymphangioma of the lateral neck. PATIENT CONCERNS: A 55-year-old man with a painless egg-sized mass in the right side of the neck that had been present for 1 month underwent physical examination, ultrasonography, computed tomography (CT), fine needle aspiration biopsy (FNAB), and intraoperative fast-frozen pathological examination, which indicated that the cystic masses in the neck were benign. However, the final pathology report identified the lateral neck masses as lymph node metastases of thyroid carcinoma. DIAGNOSIS: The patient was diagnosed with PTMC of the right lobe of the thyroid gland with lateral neck metastases. INTERVENTIONS: The patient underwent right cervical neck dissection together with a right thyroidectomy, followed by levothyroxine therapy and routine follow-up. OUTCOMES: No postoperative complications were reported, and the thyroid-stimulating hormone inhibition target was <0.1 mmol/L; there was no detectable tumor recurrence on routine clinical follow-up for up to 16 months. CONCLUSIONS: This case report emphasizes the need to consider cervical lymph node metastases of thyroid carcinoma in the differential diagnosis for patients with large, multiple, simple cystic neck masses.

Hodgkin lymphoma involving extranodal sites in head and neck: report of twenty-nine cases and review of three-hundred and fifty-seven cases.

INTRODUCTION: Hodgkin lymphoma (HL) involving the Waldeyer's ring (WR) and other extranodal head and neck sites are rare. We report our experience and PubMed literature review. METHODS: Retrospective single institution cohort study using lymphoma data base and PubMed literature search using twenty-six various search terms. RESULTS: Twenty-nine patients were treated in our institution (1975-2018). Male:Female 22:7, median age at diagnosis 33 years (15-64), stages I-II:III-IV 25:4. Sites were nasopharynx (10), tonsil (9), parotid (5), mandible (2) and others (3). 20/29 patients received radiation therapy, 22/29 received chemotherapy. Ten years overall-survival and progression-free survival are 92% and 66% respectively. PubMed search showed 8766 citations and identified 357 patients including our patients. Male:Female 199:131, median age 45 years (5-89). Stages I-II in 286 (80%). Involvement was nasopharynx 109 (30.5%), tonsil 67 (18.8%), parotid 58 (16.2%), thyroid 45 (12.6%), adenoid 10 (2.8%), mandible 10 (2.8%) and others in 58 (16.2%). Pathology: mixed cellularity 99 (27.7%), nodular sclerosis 88 (24.6%), nodular lymphocyte-predominant 56 (15.7%), lymphocyte rich 25 (7%), classical-HL-not otherwise specified 16 (4.5%) and lymphocyte depleted 7 (2%) patients. Treatment details are available for 233 patients; 165 (46%) received radiation therapy, 137 (38%) chemotherapy. Complete remission in 208 (58%), progressive disease 14 (4%), no information 135 (38%). Overall, treatment failure in 54 (15%). Thirty (8.4%) have died; 21 disease related. KM overall-survival at 5 and 10 years was 88.5% and 77.6% respectively. CONCLUSION: This largest report showed that HL involving extranodal head and neck sites is not very uncommon and has excellent prognosis.

Salivary gland hyalinizing clear-cell carcinoma with cutaneous metastasis: A rare and deceptive tumor.

Clear-cell carcinoma (CCC) is an uncommon malignant tumor of minor salivary glands. It characteristically has a low-grade morphology and a favorable outcome by most reports. An EWSR1-ATF1 fusion can be detected in the majority of cases. We present a rare case of CCC, which had an aggressive course with the development of cutaneous metastases. Practicing dermatopathologists should be aware of this tumor given its low-grade appearance and histopathologic resemblance to other primary cutaneous adnexal and metastatic neoplasms.

Cancer of unknown primary in the head and neck: Diagnosis and treatment.

Cancer of unknown primary in the head and neck is defined by the presence of cancer in one or more lymph nodes within the head and neck region, not confined to the supraclavicular region, without an identifiable primary tumor. These primary sites are increasingly being identified with the help of advanced diagnostic techniques such as endoscopy, PET/CT, the HPV test, the EBV test, evaluation of biomarkers, and pathological examination. However, the remainder of these patients fall into the category of metastatic cervical cancer of unknown primary (MCCUP). MCCUP accounts for approximately 3-5% of all head and neck squamous cell carcinomas (HNSCCs). Moreover, optimal therapy for patients with MCCUP is still controversial. The treatment options range from neck dissection alone to irradiation of the bilateral neck, with or without irradiation of plausible primary sites as well. In future, precision medicine should improve the diagnosis and methods of therapy for MCCUP patients.

Metastatic Epithelial-Myoepithelial Carcinoma in a Female Presenting with Neck Mass and Lytic Lesion in Acetabulum: A Diagnostic Challenge on Cytology.

Epithelial-myoepithelial carcinoma (EMC) is a rare, low-grade, malignant salivary neoplasm. Establishing an accurate cytological diagnosis is often challenging owing to its rarity, bland cytologic appearance and variable representation of cell populations in the smears. The diagnostic struggle is more so when the aspiration is from a metastatic site with an unknown primary, as in such cases the list of differential diagnoses expands further. A 58-year-old female presented with a low-back pain from last one month. On examination, she also had a level III, right cervical swelling for the last 20 years. Radiology revealed a lytic lesion in the left acetabulum. She had undergone surgery 35 years ago for a right-sided upper neck swelling, the medical records of which were not available. Fine needle aspiration (FNA) from the cervical swelling was performed. The smears were cellular and showed predominantly dispersed, round to polygonal tumor cells with mild pleomorphism, eccentric nuclei, coarse chromatin, occasional nucleoli and moderate cytoplasm with some showing vacuolations. The cell-block section revealed tumor cells arranged in the form of tubules lined by dual layer of tumor cells without any chondromyxoid stroma. On immunocytochemistry, the luminal cells showed positivity for CK7 (epithelial marker) and the abluminal cells showed positivity for p63 (myoepithelial marker). Based on these features, a final diagnosis of metastatic epithelial-myoepithelial carcinoma was rendered. The present report highlights the characteristic cytomorphological and immunocytochemical features of EMC and reiterates the diagnostic accuracy of FNAC for diagnosis of such challenging cases.

Neck subcutaneous nodule as first metastasis from broad ligament leiomyosarcoma: a case report and review of literature.

BACKGROUND: Leiomyosarcoma usually develops in the myometrium and is characterized by a high recurrence rate, frequent hematogenous dissemination, and poor prognosis. Metastasis is usually to lungs, liver, and bone, and occasionally to the brain, but seldom to the head and neck region. Primary leiomyosarcoma very rarely arises in the broad ligament. CASE PRESENTATION: A 54-year old woman presented to the otolaryngology department with a mass in the right posterior region of the neck 4 years after surgery for a primary leiomyosarcoma of the right broad ligament. The neck mass was removed and found to be a metastatic leiomyosarcoma. Leiomyosarcoma localizations in lungs and liver were absent. Morphological examination showed both the primary and the secondary leiomyosarcomas to have features of low-grade tumors. One year after excision of the neck mass, the patient presented with tachycardia. Echocardiography detected two intracardiac nodules suggestive of metastatic tumors. Chemotherapy was administered; the disease has been stable since then. CONCLUSIONS: We report the first case of broad ligament leiomyosarcoma with the neck subcutaneous region being the first site of secondary involvement. We speculate that the Batson venous plexus might have been the pathway of dissemination.

Metastatic Mimics of Primary Cutaneous Lesions: Averting Diagnostic Pitfalls With Significant Repercussions.

Cutaneous metastases by solid malignancies often signify advanced disease and portend severely limited survival. Appropriate diagnosis of these lesions is particularly hampered when they closely resemble primary cutaneous tumors. In this article, we present two diagnostically challenging cases of metastatic lesions to the scalp bearing striking histologic resemblance to primary cutaneous neoplasms. One case of a metastatic urothelial carcinoma showed epidermotropism as well as histologic and immunohistochemical features virtually indistinguishable from those of a poorly differentiated squamous cell carcinoma. Next generation sequencing was performed on both the primary urothelial carcinoma and scalp malignancy revealing an identical BRAF p. S467L somatic mutation, confirming the diagnosis. Another case of metastatic renal cell carcinoma showed clinical and histomorphologic features highly reminiscent of a pyogenic granuloma. These cases demonstrate the potential of metastatic lesions to assume a myriad array of innocuous disguises and underscore the vigilance required to avoid misdiagnosis. In addition, we highlight the emerging role of molecular strategies in resolving these problematic cases.

Mandibular metastasis as a presenting feature of a clival chordoma.

Chordomas are rare tumors which arise from the embryological remnants of the notochord. These tumors can potentially arise from any region within the craniospinal axis and often clinically present as a diagnostic challenge. Chordomas are rare in patients younger than 40 years of age. The most common primary cancers that metastasize to the jaw bones are the ones originating from the breast, lung, kidney adrenal, colo-rectum, or prostate. Mandibular metastasis from a primary chordoma is an extremely rare occurrence with only five prior reports, three originating from primaries in the sacrococcygeal region, one from a lumbar spine primary and the other from a primary arising from the spheno-occipital region. A literature review did not reveal any prior reports of mandibular metastasis at presentation from a clival chordoma. We possibly report the first case of such an unusual clinical scenario in a 7-year-old male child and further discuss the evaluation and management of these rare tumors.