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.

Branchiogenic cyst ‒ a rare finding in vascular surgery.

Branchiogenic cysts are benign lesions caused by anomalous development of the branchial cleft. They are typically detected in individuals aged between their twenties and forties. Ultrasonography is the first-line imaging method of choice. Surgical excision is the sole treatment modality (Tab. 1, Fig. 6, Ref. 25). Keywords: branchiogenic cyst, extirpation, ultrasonography, computed tomography.

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.

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.

Ectopic Salivary Gland - A Possible Differential Diagnosis of a Branchial Cleft Cyst.

Background: Branchial cleft cysts or fistulae are common in pediatric surgical pathology and are cured by surgery. Lesions in this area may not show the classical features of a cyst or duct lined by squamous or respiratory epithelium and other differential diagnoses should be considered. Case report: A seven-year-old otherwise healthy boy presented with bilateral swelling of the lower neck and reported intermittent secretion of clear fluid on the right side. Excision of the right sided lesion revealed an ectopic salivary gland, the excision of the left showed only subtle fibrosis. Conclusion: Ectopic salivary glands may occur in the distribution of branchial cleft remnants. Clear fluid drainage (saliva) may be a clinical clue that these are not branchial cleft cremnants.

[Malignant transformation of a branchial cleft cyst]. / Rosszindulatúan elfajult nyaki branchiogen cysta.

Branchial cleft cyst is the most common birth defect involving the neck. Malignant transformation is known, however, differentiating from a neck metastasis of a squamous cell carcinoma of unknown primary is challenging. Even though there are strict criterias, the diagnosis of this entity remains controversial. We present the case of a 69-year-old woman, who presented with a swelling under the left side of the mandible. After diagnostic workup, fine-needle aspiration biopsy raised the suspicion of a cystic squamous cell carcinoma metastasis, therefore we performed panendoscopy and modified radical neck dissection. The pathological examination confirmed branchial cleft cyst carcinoma. After surgery, the patient received adjuvant radiation and chemotherapy. During the case workup, we present the difficulties of the diagnostic process, differential diagnostic problems, and the review of the international literature. In the case of a solitary, cystic mass on the neck without a primary tumor, we should consider the possibility of a branchiogenic carcinoma. Orv Hetil. 2023; 164(10): 388-392.

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.

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.

Nasopharyngeal Presentation of a Pharyngeal Cleft Cyst in a Dog.

A 2 yr old castrated male shih tzu was presented for assessment of worsening chronic snoring since first detected at 3 mo of age. An upper respiratory endoscopic examination and a computed tomographic scan showed a well-circumscribed, fluid-filled nasopharyngeal mass located in the median plane on the nasal side of the soft palate. This lesion was removed using a ventral approach to the nasopharynx by blunt-sharp dissection from the submucosal tissues of the soft palate. Histopathology revealed a cystic lesion lined by a single layer of a pseudostratified columnar ciliated epithelium, characteristic of a pharyngeal cyst. Follow-up 5 mo after surgery revealed complete resolution of the clinical signs with no evidence of local recurrence. Pharyngeal cysts are developmental abnormalities of the branchial apparatus. Most derive from the second branchial arch and cause cysts, sinuses, and fistulae to develop in the neck region. In our case, the lesion was located in the nasopharynx, leading to snoring and exercise intolerance. This condition should be included in the differential diagnosis of suspected nasopharyngeal obstruction.

Head and Neck Cystic Lesions: A Cytology Review of Common and Uncommon Entities.

BACKGROUND: Cystic lesions of the head and neck are a diagnostic challenge since they are seen in the clinical presentation of a wide variety of conditions. Herein, common and uncommon entities that present as cystic lesions in the head and neck are reviewed. SUMMARY: In this study, peer-reviewed articles were selected using the database PubMed, Google, Google Scholar, and Scopus. Emphasis was placed on peer-reviewed articles that discuss the cytomorphology and differential diagnosis of entities that present as cystic lesions of the head and neck. In the anterior neck, both benign and malignant neoplasms can present, including papillary thyroid carcinoma (PTC), thyroid adenomatoid nodule, parathyroid cysts, and thyroglossal cysts. In the lateral neck, branchial cleft cyst, PTC, ectopic thyroid cyst, and squamous cell carcinomas (human papilloma virus and non- human papilloma virus-related) are common. Age over 40 years raises the possibility of malignancy. In the deep neck, mostly benign cystic entities occur such as a pleomorphic adenoma, paraganglioma, schwannoma, branchial cyst, epidermal inclusion cyst, and lymphoepithelial cyst. Lesions with squamous cell features can pose diagnostic dilemmas. CONCLUSION: Cytologic examination of head and neck cysts can provide valuable information regarding the nature of the cystic lesions. Information about anatomic site and clinical history can assist with the differential diagnoses. Ancillary studies can improve the diagnosis in some cases. Each case should be evaluated very carefully since there are a wide variety of congenital conditions, infectious/inflammatory conditions, benign neoplasms, and primary and secondary malignancies presenting as a cystic mass in the head and neck.

Current approach to branchial remnants in the neck.

Congenital branchial fistulas and cysts are an interesting subject in cervical pathology. There are congenital malformations with late expression in young adults that require correct diagnosis and appropriate treatment. We review essential notions of cervical embryology to understand the mechanism of occurrence of these malformations and their clinical expression. The most common cases present vestiges from the second branchial arch, with the appearance of a cystic tumor or a fistulous orifice on the anterior edge of the sternocleidomastoid muscle, at the level of the hyoid bone. Performant imagery is mandatory for appropriate diagnosis, so we recommend a cervical computed tomography (CT) scan or cervical magnetic resonance imaging (MRI) to evaluate the relations with great vessels of the neck or other lesions. The treatment implies complete surgical excision because otherwise there is a high risk of recurrence of the lesion. The differential diagnosis includes cystic lymphangioma, dermoid cyst, tuberculous adenopathy, cystic hygroma, lateral cervical cystic metastases. Histological examination is mandatory for a definite diagnosis. Also, there is a small percentage of malignancy of these malformations, but it is very important to check that all the histological diagnostic criteria for a primary branchiogenic carcinoma are accomplished. Therefore, although it is a benign cystic cervical pathology, the diagnosis and treatment must be made very accurately for a complete cure, and this review aims to summarize the current approach to branchial remnants of the neck.

First branchial arch cyst in an elderly patient: diagnostic dilemma and subsequent management.

The branchial system plays a significant role in the embryological development of the many internal and external human body structures. Failure of normal development of these systems may result in branchial system anomalies. Anomalies of the first branchial cleft are rare and account for 1-8% of all branchial anomalies. They have an incidence of 1 per 1 million births, most of which are diagnosed in early childhood. We present an unusual case of a first branchial arch cyst in an elderly gentleman: a 65-year-old man who presented with a persistent swelling in the left pre-auricular region with no associated sinus, fistulae or lymphadenopathy and with an intact facial nerve. Investigations including fine needle aspiration, ultrasound and magnetic resonance imaging led to the diagnosis of a lesion of salivary origin and an extracapsular dissection was undertaken. The histological appearance on excision was, however, in keeping with a first arch branchial cyst. In conclusion, the nonspecific clinical and radiological presentation of first branchial arch anomalies may lead to difficulty and often delay in the diagnosis of these lesions, particularly in elderly patients as it is more often associated with childhood and adolescence. A high level of suspicion is mandatory to prevent inappropriate management in the form of incision and drainage, which further increases the risk of recurrence and facial nerve injury at the time of formal excision due to scarring.

Prevalence of cystic metastases in a consecutive cohort of surgically removed branchial cleft cysts.

BACKGROUND: Solitary cystic lesion of the neck may often be the only initial presenting symptom for branchial cleft cysts and cystic metastases. AIMS/OBJECTIVES: To analyse the malignancy rate detected in patients undergoing surgical treatment for lateral branchial cleft cyst. MATERIAL AND METHODS: The records of all patients with surgical procedure code ENB40 (Excision of lateral branchial cleft cyst- or fistula) between 2003 and 2019 were reviewed. After excluding 150 patients, 436 patients were included for final analysis. Re-evaluation of the cytology including HPV-analysis was performed in those who had a malignant cyst. RESULTS: Cystic metastases were demonstrated histologically after surgical excision in 13 patients (3%). In patients over 18 years of age, the prevalence of cystic metastasis regardless of the primary tumour type was 3.3%. CONCLUSION AND SIGNIFICANCE: When the investigation protocol for solitary cystic lesions of the neck is followed, the negative predictive value for malignancy is 97%. All adult patients with a cytologic verified diagnosis of branchial cyst should be examined with HPV-analysis of the cystic sample before excision of the cyst. Failure of predicting a malignancy is often associated with cytology of poor cellularity which may be improved by more frequent use of ultrasound guided fine-needle aspiration cytology (FNAC).

Branchiogenic carcinoma with rapid growth and skin involvement: a case report.

ABSTRACT: Branchiogenic carcinoma (BC) is an extremely rare and still controversial clinic entity with few cases reported in literature. This malignant squamous epithelial wall degeneration of a pre-existing second branchial cleft cyst (SBCC) was first described by Von Volk-mann in 1882. Here we present a case of cervical cystic mass that was histologically diagnosed as a primary branchial cleft cyst carcinoma. This is the first documented cases of primary BC presenting with skin involvement on initial examination.

Primary branchiogenic carcinoma: malignant degeneration of a branchial cyst, a case report.

BACKGROUND: Primary branchiogenic carcinoma (PBC) is an extremely rare and poorly documented disease developed from a brachial cleft cyst. CASE: A 51-year-old patient was referred to our unit for an upper neck mass. PBC was confirmed in accordance with Kahfif's diagnostic criteria. Prophylactic selective neck dissection was performed in a second-stage surgery to ensure the complete removal of the neoplasm. Branchiogenic origin with lymphoid tissue was confirmed in the "host cyst" after histological examination and no other tumors were found elsewhere. Regular follow up documented no relapse 12 months after surgery. CONCLUSIONS: Although rare, PBC must be suspected in presence of cervical masses, especially in patients older than 40 years. A standardized treatment algorithm still lacks, but prophylactic selective neck dissection could be considered as the first line choice after the diagnosis has been confirmed.

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.

[Voluminous parotid cyst of the first branchial arch: a case report]. / Enorme kyste parotidien du premier arc branchial: à propos d´un cas.

Parotid branchial cysts are rare and poorly known congenital malformations of the first branchial cleft. They are characterized by three types of manifestations which may be associated to it or isolated, including inflammatory swelling of the subauricular and inferior portion of the parotid with or without cervico-cutaneous fistula projecting into the cervico-mandibular area and a fistula in the floor of the external auditory canal with or without otorrhea, with or without pretimpanic bridle on otoscopy. They often go unnoticed, except for superinfections. Diagnosis is based on interview, the occurrence of recurrent abscesses or superinfections. No complementary imaging examination should be systematically performed. In atypical forms, ultrasound as well as magnetic resonance imaging (MRI) could be necessary, particularly in patients with parotid swellings, in order to confirm cystic structure. Abscesses and recurrent superinfections are the most common complications. Treatment is based on surgical resection. We report the case of a patient with voluminous parotid cyst of the pharyngeal arch.