Adenocarcinoma arising in branchioma with a KRAS and TP53 mutation.

Branchioma is a rare benign neoplasm occurring in the lower neck. Occurrence of malignant neoplasms arising in branchioma is extremely rare. Here, we report a case of adenocarcinoma arising in branchioma. A 62-year-old man had a right supraclavicular mass measuring 7.5 cm in diameter. The tumor contained an adenocarcinoma component encapsulated in a benign branchioma component. The adenocarcinoma component consisted of high- and low-grade components, with the former accounting for 80% of the adenocarcinoma. The high-grade component was immunohistochemically characterized by diffuse strong p53 expression, while the low-grade component and branchioma component were negative for p53. Targeted sequencing analysis for the branchioma and adenocarcinoma components revealed that the adenocarcinoma component harbored pathogenic mutations in KRAS and TP53. No definitive oncogenic drivers were detected in the branchioma component. Based on these immunohistochemical and molecular findings, we suggest that the KRAS mutation contributed to the pathogenesis of the adenocarcinoma, and the TP53 mutation played a key role in the transition from low-grade to high-grade adenocarcinoma.

Surgical Management of an Intrathoracic Branchial Cyst in a Yellow-crested Cockatoo (Cacatua sulphurea).

A 40-year-old, female lesser crested cockatoo (Cacatua sulphurea) was presented with a complaint of hyporexia and sudden onset of sneezing and wheezing. Physical examination revealed mild stertorous inhalation, and the apex of the heart was palpable caudoventral to the distal tip of the sternum. Projection radiographic images showed a soft tissue mass displacing the heart and the thoracic portion of the trachea. A subsequent computed tomography series revealed a single, large, and predominantly encapsulated soft-tissue mass. The mass was contained within the cranial thoracic region and occupied most of the anatomic location of the thoracic portion of the clavicular air sac, extending around a portion of the trachea. A surgical exploratory procedure was performed, with a thoracic inlet thoracotomy, and the mass was found to be cystic and deeply attached to surrounding tissues at its caudal-most aspect. Complete excision was not possible, and the mass was drained and an incomplete resection was accomplished with approximately one-half of the cystic structure removed and submitted for histopathology. The mass was found to be benign, epithelial-lined, dense, fibrous connective tissue that would be consistent with a branchial cyst.

Branchial cleft-like cysts in Hashimoto's thyroiditis: A case report and literature review.

We report an extremely rare case of branchial cleft-like cysts in Hashimoto's thyroiditis. The patient was a 77-year-old man with a growing mass in the anterior neck. Ultrasonography and computed tomography revealed a cystic lesion with septum in the left thyroid and multiple small cystic lesions in the right thyroid. Lymph node swelling of the cervical region, supraclavicular fossa and submandibular region was also observed. Left thyroidectomy and lymph node dissection were performed. Histologically, cysts were lined by stratified squamous epithelium and dense lymphoid tissue having conspicuous follicle formation surrounded the epithelial lining. Solid cell nest (SCN)-like aggregations were seen in the thyroid parenchyma adjacent to the cyst walls and a small number of thyroid follicles were observed in the fibrous wall. Immunohistochemically, it is suggested that both the cyst lining and SCN-like aggregations are originally from thyroid follicles. Although, the exact histogenesis of branchial cleft-like cysts remains unclear, there are probably two different processes for its development, one is of branchial cleft origin and the other is mere squamous metaplasia, while in our case the latter is suggested. Herein, we report our new case and update information about branchial cleft-like cysts that appears in the literature.

Branchioma: immunohistochemical and molecular genetic study of 23 cases highlighting frequent loss of retinoblastoma 1 immunoexpression.

Branchioma is an uncommon benign neoplasm with an adult male predominance, typically occurring in the lower neck region. Different names have been used for this entity in the past (ectopic hamartomatous thymoma, branchial anlage mixed tumor, thymic anlage tumor, biphenotypic branchioma), but currently, the term branchioma has been widely accepted. Branchioma is composed of endodermal and mesodermal lineage derivatives, in particular epithelial islands, spindle cells, and mature adipose tissue without preexistent thymic tissue or evidence of thymic differentiation. Twenty-three branchiomas were evaluated morphologically. Eighteen cases with sufficient tissue were assessed by immunohistochemistry, next-generation sequencing (NGS) using the Illumina Oncology TS500 panel, and fluorescence in situ hybridization (FISH) using an RB1 dual-color probe. All cases showed a biphasic morphology of epithelial and spindle cells with intermingled fatty tissue. Carcinoma arising in branchioma was detected in three cases. The neoplastic cells showed strong AE1/3 immunolabeling (100%), while the spindle cells expressed CD34, p63, and SMA (100%); AR was detected in 40-100% of nuclei (mean, 47%) in 14 cases. Rb1 showed nuclear loss in ≥ 95% of neoplastic cells in 16 cases (89%), while two cases revealed retained expression in 10-20% of tumor cell nuclei. NGS revealed a variable spectrum of likely pathogenic variants (n = 5) or variants of unknown clinical significance (n = 6). Loss of Rb1 was detected by FISH in two cases. Recent developments support branchioma as a true neoplasm, most likely derived from the rudimental embryological structures of endoderm and mesoderm. Frequent Rb1 loss by immunohistochemistry and heterozygous deletion by FISH is a real pitfall and potential confusion with other Rb1-deficient head and neck neoplasms (i.e., spindle cell lipoma), especially in small biopsy specimens.

Branchial cleft cyst and branchial cleft cyst carcinoma, or cystic lymph node and cystic nodal metastasis?

BACKGROUND: Lateral cervical cysts are usually considered as of branchial cleft origin, despite many studies showing that branchial cysts do not arise from the remnants of the branchial apparatus. In the same way, some authors still consider that a true clinicopathological entity such as 'branchial cleft cyst carcinoma' could exist, at least in theory. Despite insufficient evidence in support of the branchial theory, a number of publications continue to emphasise this concept. METHODS: A literature review of articles in Medline and PubMed databases was carried out to retrieve papers relevant to the topic. RESULTS AND CONCLUSION: The evidence from lateral cervical cyst studies and knowledge about cystic metastasis of Waldeyer's ring could be applicable for both diagnoses. Terms such as 'branchial cleft cyst' and 'branchial cleft cyst carcinoma' are confusing and misleading, and it is questionable as to whether their usage is still tenable.

Lateral cystic neck masses in adults: a ten-year series and comparative analysis of diagnostic modalities.

BACKGROUND: In adults, the solitary lateral cystic neck mass remains a diagnostic challenge with little solid material to target for cytology and few clues on imaging modalities to suggest underlying malignancy. METHOD: This study was a retrospective review of patients presenting with a lateral cystic neck mass to a tertiary academic head and neck centre over a 10-year period. RESULTS: A total of 25 of 157 cystic lesions were subsequently malignant on paraffin section histopathology, with the youngest patient being 42 years. In the age cohort over 40 years, 30 per cent of males and 10 per cent of females were diagnosed with malignancy. The ipsilateral palatine tonsil was the most common primary site (50 per cent). A total of 85 per cent of cases demonstrated integrated human papillomavirus infection. Age, male sex and alcohol were significant risk factors on univariate analysis. Ultrasound-guided fine needle aspiration cytology and magnetic resonance imaging represented the most accurate pre-open biopsy tests. CONCLUSION: The authors of this study advocate for a risk-stratified, evidence-based workup in patients with solitary lateral cystic neck mass in order to optimise timely diagnosis.

Branchioma with a nested/organoid morphology: molecular profiling of a distinctive potentially misleading variant and reappraisal of potential relationship to CD34-positive/Rb1-deficient tumors of the neck.

Branchioma (previously called ectopic hamartomatous thymoma, branchial anlage mixed tumor, or thymic anlage tumor) is a rare lower neck lesion with an adult male predominance and an uncertain histogenesis. Except for 4 cases, all branchiomas described in the literature were benign. Recently, HRAS mutation was detected in one case, but still little is known about the molecular genetic background of this rare entity. We herein report the histological, immunohistochemical, and molecular genetic analysis of a branchioma with a nested/organoid (neuroendocrine-like) morphology in a 78-year-old man. Histology revealed classical branchioma areas merging with nested/organoid cellular component lacking conventional features of malignancy. Immunohistochemistry was positive for high-molecular-weight cytokeratins. CD34 was expressed in the spindle cell component. Moreover, the tumor cells showed near-complete loss of retinoblastoma (RB1) expression (<1% of cells positive). All neuroendocrine markers (synaptophysin, chromogranin, and INSM1) were negative. Next-generation sequencing (TSO500 Panel) revealed 5 pathogenic/likely pathogenic mutations including 1 mutation in KRAS and 2 different mutations in each of MSH6 and PTEN. FISH and DNA sequencing were negative for RB1 gene alterations. To our knowledge, this is the first report of a branchioma showing misleading nested/organoid morphology and the first report on Rb1 immunodeficiency in this entity, in addition to multiple gene mutations revealed by NGS.

Persistent brachial cleft as an infrequent cause of infraglottic stridor and airway obstruction in a 24 year old woman. A case report.

BACKGROUND: We present the case of a 24-year-old woman with respiratory distress associated with a cyst of the fourth branchial cleft that displaced and compressed the upper airway, so the cervical mass was surgically resected, the patient recovered completely. CASE PRESENTATION: We present the case of a 24 year old female no other pertinent medical history who presents to the emergency department of way outpatient to respiratory distress associated with a cervical mass. A computed tomography (CT) scan shows a right cervical cystic mass that was displacing and compressing the upper airway. A total resection of the cystic mass was performed, after which the patient recovered completely. The histopathological analysis indicated a branchial cleft cyst which, due to its location, was thought to be the fourth branchial cleft, a rare congenital anomaly. CONCLUSIONS: Fourth branchial cleft cysts are rare malformations. They should be taken into consideration in the differential diagnosis of cervical masses in young adults, especially in situations of potentially life threatening airway compromise where an emergent procedure should be performed to guarantee the patient's life, the diagnosis is based on an adequate history and physical examination, with the support of imaging studies, with CT scan imaging being preferred as it provides information for surgical planning. Treatment is based on complete resection of the cystic mass, which relieves the symptoms of mass effect and decreases the risk of recurrence.

Identification of a branchial cleft anomaly via handheld point-of-care ultrasound.

Aim of the study: Branchial anomalies result from incomplete obliteration of the branchial arch structures during embryogenesis. Second branchial arch anomalies are commonly found on the lower third of the neck, with an opening at the anterior border of the sternocleidomastoid muscle, and may drain secretions or purulent material. This case demonstrates the use of handheld point-of-care ultrasound to aid in the diagnosis of a branchial anomaly. Case description: The patient presented with a "hole" in the neck with intermittent drainage from the site. A 2 mm defect in the skin was noted anterior to the sternocleidomastoid muscle. A handheld ultrasound system was used to identify a well-defined, hypoechoic, cyst-like structure. Given the history, physical findings, and point-of-care ultrasound imaging, the diagnosis of a second branchial cleft sinus was made. Conclusions: The use of point-of-care ultrasound and knowledge of the sonographic characteristics of these lesions can assist the physician in the diagnosis of branchial arch anomalies.

Cervical Thymic Cyst with parathyroid tissue - a diagnostic conundrum.

Cervical thymic cysts are relatively rare benign cystic lesions that tend to be diagnosed clinically as branchial cysts, which usually present as painless, enlarging neck masses. They can occur anywhere along the normal path of descent of thymic primordia from the angle of the mandible to the sternal notch, with mediastinal extension observed in approximately 50% of cases. They are usually seen in the first decade of life on the left side with a male predominance. Here we report a case of a 15-year-old boy who presented to the hospital with left-sided neck swelling for about 2 months. The neck's contrast-enhanced computed tomography (CECT) revealed a large, well-defined cystic swelling in the left neck region, showing peripheral enhancement, seen from the submandibular region to the superior mediastinum extending into the retrosternal region. Direct fine needle aspiration (FNA) was done, which showed a benign lesion with inflammatory and cystic characteristics, leading to the possibility of a branchial cyst. The cyst was completely excised surgically. Histopathology showed a thymic cyst with parathyroid tissue. The presence of thymic tissue with Hassall's corpuscles is essential for the diagnosis. Knowledge of the clinical presentation, cyto-histological findings, and differential diagnosis of cystic cervical lesions in the pediatric population is important to diagnose this rare entity. Hence, though uncommon, when one comes across a cystic cervical region mass in children, a diagnosis of cervical thymic cyst should be kept in mind. Nonetheless, a definitive diagnosis depends on imaging findings as well as intraoperative findings and histopathological examination.

Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: The Neck and Lymph Nodes, Metastasis, and Melanocytic Tumors.

The changes made in the fifth edition of the WHO Classification of Head and Neck Tumors demonstrate the recent diagnostic, histopathological, and molecular advances in the field, and this updated information will hopefully lead to improved and standardized tumor subtyping. This review summarizes the changes related tumors and tumor-like lesions of the neck and lymph nodes (Chapter 11), metastasis to the head and neck region (Chapter 15), and melanocytic tumors (Chapter 10).

The first Korean case of cutaneous lung tissue heterotopia.

Cutaneous lung tissue heterotopia is a very rare disorder where mature lung tissues develop in the skin. This is only the second known report of cutaneous lung tissue heterotopia, with the first by Singer et al. in 1998. A newborn infant had a hemangioma-like, freely movable mass connected to the anterior aspect of the sternal manubrium. Pathologic findings showed mature lung tissues with bronchi, bronchioles, and alveoli through the dermis and subcutis, and it was diagnosed as cutaneous lung tissue heterotopia. Cutaneous lung tissue heterotopia is hypervascular, so grossly it looks like a hemangioma. It can be differentiated from pulmonary sequestration, teratoma, bronchogenic cyst, and branchial cleft cyst by histology and the location of the mass. We describe the clinical, radiologic, and pathologic findings of a cutaneous lung tissue heterotopia, the first reported in Korea.

Biphenotypic Branchioma: A Better Name Than Ectopic Hamartomatous Thymoma for a Neoplasm with HRAS Mutation.

Ectopic hamartomatous thymoma is a rare neck lesion originally thought to represent a non-neoplastic hamartoma, even though thymic origin has been questioned, and there is uncertainty about whether the lesion is a neoplasm. We investigated the genetics by performing targeted next generation sequencing (NGS). Three cases were identified from the authors' consultation files. A custom, targeted NGS panel including 1385 pan-cancer-related genes was performed on all cases. Three patients included 2 males and 1 female, aged 50, 58 and 70 years, respectively (mean 59.3 years), with tumors arising in the low anterior neck. All cases showed classical histologic features of EHT, with one case showing intraductal carcinoma in association with the EHT. By targeted NGS, one case harbored a hotspot HRAS mutation (p.Gln61Lys), while the other two cases only showed non oncogenic variants. Dual mesoderm and endoderm derivation/differentiation (biphenotypic) has been previously recognized, with epithelial and myoepithelial components, and arising from the apparatus contributing to neck development (branchial apparatus). Thus, EHT has been shown to have genetic alterations in HRAS. These findings, without evidence of thymic derivation or an ectopic tissue location, strongly support that EHT is a true neoplasm. The name biphenotyic branchioma more correctly reflects the true nature of this dual mesoderm and endoderm derived tumor occurring in the lower neck.

Branchial cleft cyst in the parotid gland in a human immunodeficiency virus-negative patient.

In branchial lymphoepithelial cyst (BLEC), which is also known as branchial cleft cyst, the remnants of a branchial arch develop into a cyst, causing swelling. The first case of BLEC in the parotid gland was reported by Hildebrant in 1895. Since then, BLEC in the parotid gland has continued to be reported, but in rare cases. A 45-year-old man presented to our hospital with a swelling of the left cheek of approximately 6 months' duration. The patient underwent a superficial parotidectomy and was pathologically diagnosed with BLEC. Of note, this was the first case of non-human immunodeficiency virus (HIV)-related BLEC of the parotid gland in South Korea. BLEC is a benign condition, but its treatment depends on the presence of HIV infection. In HIV-negative patients, BLEC does not require a further work-up to evaluate metastasis. Our case report describes the diagnosis and treatment of BLEC in a patient without HIV.

Incidence and clinical predictors of cystic squamous cell carcinoma metastases in lateral cervical cysts.

OBJECTIVE: This study aimed to determine the incidence of metastatic squamous cell carcinoma in patients with an isolated cervical cystic mass, and to describe the clinical features that might predict the origin of cystic tumours. METHOD: Adult patients with isolated lateral cervical cystic masses who were scheduled for surgery from 1st January 2010 to 31st August 2016 in two tertiary care referral centres in Slovakia were analysed retrospectively. RESULTS: The incidence of cystic metastases in the whole cohort and in patients aged over 40 years were 9.9 per cent and 18.5 per cent, respectively. The incidence in patients aged over 40 years (18.5 per cent) was statistically significant (p = 0.003). CONCLUSION: The incidence of cystic squamous cell carcinoma metastases in lateral cervical cysts in patients aged over 40 years is high enough to call for excisional biopsy with frozen section, panendoscopy with direct biopsies, tonsillectomy and even neck dissection in cases of histologically confirmed carcinoma.

Ectopic Warthin's Tumour Masquerading As Infected Branchial Cyst.

Salivary gland tumours are relatively uncommon but they present globally regardless of age. Most of these tumours are benign and involve the parotid gland. Though strictly confined to the parotid gland, Warthin's tumours can exceptionally present at an ectopic site of head and neck. Of particular significance is its striking similarity with a lymph node, an inclusion cyst, branchial cyst or a malignant mass, especially when it presents in the upper cervical region.

Ectopic Hamartomatous Thymoma: A Review Of The Literature With Report Of New Cases And Proposal Of A New Name: Biphenotypic Branchioma.

Ectopic hamartomatous thymoma (EHT) is a rare benign neoplasm of the lower neck suggesting branchial origin. Despite use of the term thymoma in the nomenclature, there is no evidence of thymic origin or differentiation. It affects middle-aged adults with a remarkable male predominance. To date less than 80 cases have been reported in the English literature. We present here two additional cases of EHT. The first is a benign case in a 31-year-old man, showing typical histological features. The second is a malignant case in a 70-year-old woman, showing intraductal carcinoma arising in intimate association with an EHT. These cases are presented in the context of a review of cases reported in the English literature. The exact origin has not been identified, but is considered to be of branchial apparatus, creating a quandary about the best terminology. Recently, the designation "branchial anlage mixed tumor" or "thymic anlage tumor" were proposed, but do not quite reflect the true nature of the neoplasm. To avoid taxonomic confusion, international consensus on terminology is desired. As this entity is a neoplasm that shows dual mesoderm and endoderm derivation/differentiation, we propose a new name "biphenotypic branchioma."

Cervical Thymic Cyst with parathyroid tissue - a diagnostic conundrum

Cervical thymic cysts are relatively rare benign cystic lesions that tend to be diagnosed clinically as branchial cysts, which usually present as painless, enlarging neck masses. They can occur anywhere along the normal path of descent of thymic primordia from the angle of the mandible to the sternal notch, with mediastinal extension observed in approximately 50% of cases. They are usually seen in the first decade of life on the left side with a male predominance. Here we report a case of a 15-year-old boy who presented to the hospital with left-sided neck swelling for about 2 months. The neck's contrast-enhanced computed tomography (CECT) revealed a large, well-defined cystic swelling in the left neck region, showing peripheral enhancement, seen from the submandibular region to the superior mediastinum extending into the retrosternal region. Direct fine needle aspiration (FNA) was done, which showed a benign lesion with inflammatory and cystic characteristics, leading to the possibility of a branchial cyst. The cyst was completely excised surgically. Histopathology showed a thymic cyst with parathyroid tissue. The presence of thymic tissue with Hassall's corpuscles is essential for the diagnosis. Knowledge of the clinical presentation, cyto-histological findings, and differential diagnosis of cystic cervical lesions in the pediatric population is important to diagnose this rare entity. Hence, though uncommon, when one comes across a cystic cervical region mass in children, a diagnosis of cervical thymic cyst should be kept in mind. Nonetheless, a definitive diagnosis depends on imaging findings as well as intraoperative findings and histopathological examination.

Cisto branquial da 4ª fenda ­ relato de caso / Branchial cyst 4th cleft ­ case report

Introdução: Os cistos branquiais são tumores congênitos laterais, resultantes de defeitos de desenvolvimento embrionário que afetam os arcos branquiais.1 As anomalias congênitas cervicais são mais comumente diagnosticadas nos primeiros anos de vida. Objetivo: Informar, discutir e analisar condutas para tratamento desse tipo de cisto congênito. Método:Relato de caso e análise de dados, diagnósticos e conduta baseada na literatura referente a Cisto Branquial da 4° Fenda. Resultados:Os cistos podem se manifestar tardiamente, mas as fístulas são, quase sempre, diagnosticadas ao nascimento ou na infância.São extremamente raros, estima-se que 95% das anomalias das fendas branquiais sejam da 2ª fenda; das 5% restantes, quase todas são da 1ª ou 3ª fenda.O diagnóstico é primariamente clínico, mas a ultrassonografia pode auxiliar no diagnóstico diferencial de um cisto branquial. O tratamento das anomalias branquiais é a excisão cirúrgica. Lactente sexo feminino, 9 meses de idade em acompanhamento de cisto branquial com conduta conservadora. O surgimento da massa se deu logo ao nascimento, havendo drenagem espontânea do cisto para o esôfago alguns dias depois. Após nove meses paciente retorna devido aumento progressivo da lesão que correlacionando com exame físico, exames de imagem levaram ao diagnóstico de cisto de 4º fenda branquial. Realizada cirurgia para remoção de Cisto juntamente com retirada de lobo esquerdo da tireoide (tireoidectomia parcial). Conclusão:Após a exerese da lesão paciente evoluiu satisfatoriamente sendo encaminhado para enfermaria e posteriormente alta com acompanhamento ambulatorial com pediatra geral.

Introduction: Branchial cysts are congenital tumors, resulting from embryonic defects that affect the branchial arches. Congenital cervical abnormalities are usually diagnosed in the first years of life. Objective: To inform, discuss and analyze treatment approaches for this type of congenital cyst. Method: Case report and analysis of data, diagnoses and approaches based on the literature addressing Fourth Branchial Cleft Cysts. Results: Cysts can manifest late, but fistulas are almost always diagnosed at birth or in childhood. They are extremely rare: it is estimated that 95% of branchial cleft anomalies involve the second cleft; of the remaining 5%, almost all arise from the first and third clefts. There are about 45 cases of fourth cleft cysts reported in the literature. The diagnosis is primarily clinical, but the ultrasound can be used for the differential diagnosis of a branchial cyst. Computed tomography will show air-fluid level in the anterior portion of the neck, in front of the thyroid and trachea, which may compress the trachea, causing respiratory distress in childhood. The treatment of branchial anomalies is surgical excision. A 9-month old female patient was being followed up after conservative treatment of a cervical mass (branchial cyst). The cyst appeared immediately after birth, but there was there was spontaneous drainage of the cyst into the esophagus a few days later. After nine months, the patient returned due to a progressive increase of the lesion, which, after physical examination and imaging exams, led to the diagnosis of a fourth branchial cleft cyst. A surgical procedure was performed to remove the cyst along with the left thyroid lobe (partial thyroidectomy). Conclusion: After the excision of the lesion, the patient made a good recovery. She was then referred to the infirmary and later discharged with outpatient follow-up by a general pediatrician.

Case report of a p16INK4A-positive branchial cleft cyst.

OBJECTIVE: To report the occurrence of a concurrent oropharyngeal papilloma and branchial cleft cyst linked by p16(INK4A) and human papillomavirus immunohistochemistry. CASE REPORT: A 42-year-old woman presented with a 1-month history of a left lateral neck mass. Contrast enhanced computed tomography showed a hypodense lesion 20 mm in diameter anteromedial to the left sternocleidomastoid muscle. Ultrasound-guided fine needle aspiration suggested a branchial cleft cyst. Panendoscopy was performed at the time of neck mass removal, and a papillomatous lesion was removed from the left hypopharynx. Histopathological analysis showed the neck lesion to be a branchial cyst containing lymphoid tissue, and the oral lesion to be a squamous papilloma. Immunohistochemical analysis showed both the branchial cleft cyst and papilloma to be positive for p16(INK4A) expression and human papillomavirus DNA. CONCLUSION: Histological and immunohistochemical analyses support the cystic transformation of lymph nodes, or the 'Inclusion Theory', as the aetiology of branchial apparatus anomalies, and raise the possibility that human papillomavirus infection may play a much larger role in disease of the head and neck than previously supposed.