Cystic neck lesions: clinical, radiological and differential diagnostic considerations

Solitary cystic masses of the lateral neck in an adult patient can pose a diagnostic dilemma. Malignancy must be ruled out since metastases arising from H&N cancers may mimic the presentation of benign cystic masses. Only a small number of studies have investigated the diagnostic management and malignancy rate of clinically benign solitary cervical cystic lesions. There are no established guidelines for the diagnostic evaluation. Retrospective review of the clinical, cytological, radiological, and pathological records of all adult patients (> 18years) operated on for second branchial cleft cysts (BrCC) between 1/2008-2010/2016. Patients with apparent primary H&N malignancy, history of H&N cancer or irradiation, preoperative fine needle aspiration (FNA) of highly suggestive or confirmed malignancy, missing pertinent data, or age less than 18years were excluded from analysis. 28 patients were diagnosed as having BrCC. The diagnosis was based on clinical findings, FNA cytology, and typical sonographic features. The histologic analysis determined an overall rate of malignancy of 10.7% (3/28): two patients had metastatic papillary thyroid carcinoma, and one patient had metastatic tonsillar squamous cell carcinoma. Purely cystic features on pre-operative ultrasound was the only significant predictor for true BrCC on final histology (p = .02). Occult malignancy is not rare among adult patients presenting with a solitary cystic mass of the lateral neck. A diagnostic algorithm is proposed. Further studies are needed to establish the appropriate workup and management of an adult patient presenting with a solitary cystic mass of the lateral neck.

SummaryWe report a case of metastatic papillary thyroid carcinoma presenting with a recurrent right-sided cervical lymph node necrotic cyst. A 55-year-old woman presented with a 3-month history of a right-sided upper neck mass following an upper respiratory tract infection. Past medical history includes a right-sided nephrectomy secondary to a benign renal tumor and hypertension. She was evaluated by Otolaryngology, and fine-needle aspiration was performed. The mass recurred 2 months following aspiration. Ultrasound of the neck showed a 2.2 × 1.4 × 1.9 cm right cervical lymph node with a small fatty hilum but a thickened cortex. Neck computed tomography (CT) scan showed a well-defined 2.3 cm mass in the right upper neck corresponding to a necrotic cervical lymph node at level IIA. It also revealed a 7 mm calcified left thyroid nodule. Cytology revealed a moderate collection of murky fluid with mildly atypical cells presumed to be reactive given the clinical history of infection. The cyst had re-grown 2 months following aspiration. Excisional biopsy was performed and revealed metastatic classic papillary thyroid carcinoma (PTC). Subsequently, a total thyroidectomy and right neck dissection was performed. Pathology confirmed metastatic unifocal classic PTC of the right thyroid lobe and two lymph node metastases out of a total of 17 resected lymph nodes. The patient underwent radioactive iodine ablation. Subsequent I-131 radioiodine whole-body scan showed no evidence of metastases. In conclusion, metastatic PTC should be considered in the differential diagnosis of a recurrent solitary cystic cervical lymph node.Learning points:Metastatic PTC should be considered in the differential diagnosis of a recurrent solitary cystic cervical lymph node.A dedicated thyroid ultrasound is the preferred modality for identifying thyroid lesion over computed tomography.There is a risk of non-diagnostic cytology following FNA for cystic neck lesions, largely predicted by the cyst content of the nodule.

Cystic Metastatic Nasopharyngeal Carcinoma Presenting as Branchial Cleft Cyst: Report of Two Cases and Review of the Literature

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Squamous papilloma arising from within a branchial cleft cyst

Patients with previously resected papillary thyroid carcinoma (PTC) are monitored for disease recurrence/metastasis by ultrasound surveillance and fine-needle aspiration (FNA) cytology. However, accurate diagnosis in lesions with cystic degeneration may be difficult due to scant cellularity. In the current study, the authors evaluated thyroglobulin in FNA (Tg-FNA) for detecting metastatic and/or recurrent PTC in patients with cystic neck lesions after thyroidectomy. The pathology records were retrospectively searched for patients with previously resected PTC and subsequent Tg-FNA on a cystic neck mass. Tg-FNA was measured in needle rinses using a Tg assay. The ultrasound findings, Tg-FNA concentrations, and cytological and follow-up histological diagnoses were correlated. A total of 21 FNA specimens of cystic lesions from 19 patients were identified. Of 7 cases with cytologic and subsequent histologic diagnoses of metastatic PTC, the median Tg-FNA level was 100,982 ng/mL. Of 8 cytologically benign cases, 7 cases had Tg-FNA levels < 0.2 ng/mL, and 1 aberrant case demonstrated elevated Tg-FNA of > 1000 ng/mL. For 6 cytologically equivocal cases, including 3 classified as atypical/suspicious for carcinoma, 2 classified as insufficient/acellular debris, and 1 classified as spindle cell neoplasm, 4 patients demonstrated markedly elevated Tg-FNA levels (> 150 ng/mL) with subsequent surgical confirmation of metastatic PTC, whereas 2 patients had Tg-FNA levels of < 0.2 ng/mL with negative follow-up. Using a cutoff value of 0.2 ng/mL, Tg-FNA demonstrated a sensitivity of 100% and specificity of 87.5%. Tg-FNA is a useful ancillary test that improves the detection of cystic PTC metastases. Particularly in cytologically nondiagnostic cases, the measurement of Tg-FNA helps to distinguish benign from malignant cystic lesions.

Second branchial cleft cysts are the most common type of branchial cleft cysts as they make up approximately 95% of all cases. These are congenital conditions that occur in the upper lateral neck just anterior to the sternocleidomastoid muscle and caused by fluids filling spaces during early embryonic development. We present a case of atypical presentation of second branchial cleft cysts in 40 year’s patient, A surgical intervention was performed with complete excision of the cysts. Many of branchial cleft cysts would go unnoticed. However, upper respiratory tract infection can cause a sudden and significant increase in the size of the cyst because of the lymphoid tissue beneath the epithelium, The Differential diagnosis would include lymphadenopathy, lipoma, nerve sheath tumor, inflammatory lesions, carotid body tumor, external laryngocele, cystic hygroma, metastatic squamous cell carcinoma, tuberculosis-related, HIV-related lymphadenopathy, sarcoidosis, cat-scratch disease, lymphoma, and papillary thyroid carcinoma metastasis. Surgical excision is the only known treatment for second branchial cleft cysts; moreover, a complete removal of second bronchial cyst cleft is of paramount importance since it is key to preventing any recurrence of the disease.

Papillary thyroid carcinoma (PTC) in a branchial cleft cyst (BCC) is exceedingly rare. This case report describes a 53-year-old male with a BCC containing PTC. Despite normal preoperative thyroid imaging, total thyroidectomy revealed multifocal bilateral micropapillary thyroid carcinoma with a contralateral metastatic lymph node, suggesting an aggressive disease course. This finding supports the likelihood that thyroid gland carcinoma metastasized to the BCC. However, the possibility of a primary tumor arising from ectopic thyroid tissue within the cyst cannot be excluded. To our knowledge, this is the 11th reported case of papillary thyroid cancer noted in a BCC. The patient underwent successful treatment, including radioiodine ablation, highlighting the importance of thorough diagnostic evaluation and management in such rare presentations. While most BCCs are benign, PTC can very rarely present within BCC. Metastatic PTC with a necrotic lymph node is often misdiagnosed as BCC, both radiographically and histologically. Since PTC arising as a primary tumor from ectopic thyroid tissue within a BCC is extremely rare, total thyroidectomy should be considered even in patients with radiographically normal thyroid to rule out micropapillary primary thyroid tumors. A thyroglobulin assay from the needle washout of a fine-needle aspiration of a BCC may help preoperatively identify differentiated thyroid cancers. Micropapillary thyroid cancers (<1 cm) are usually indolent, but some may show nodal metastases and clinical progression.

The separation of branchial cleft cysts from metastatic cystic squamous cell carcinomas in adults can be clinically and cytologically challenging. Diagnostic accuracy for separation is reported to be as low as 75% prompting some authors to recommend frozen section evaluation of suspected branchial cleft cysts before resection. We evaluated 19 cytologic features to determine which were useful in this distinction. Thirty-three cases (21 squamous carcinoma and 12 branchial cysts) of histologically confirmed cystic lesions of the lateral neck were graded for the presence or absence of 19 cytologic features by two cytopathologists. The cytologic features were analyzed for agreement between observers and underwent multivariate analysis for correlation with the diagnosis of carcinoma. Interobserver agreement was greatest for increased nuclear/cytoplasmic (N/C) ratio, pyknotic nuclei, and irregular nuclear membranes. Recursive partitioning analysis showed increased N/C ratio, small clusters of cells, and irregular nuclear membranes were the best discriminators. The distinction of branchial cleft cysts from cystic squamous cell carcinoma is cytologically difficult. Both digital image analysis and p16 testing have been suggested as aids in this separation, but analysis of cytologic features remains the main method for diagnosis. In an analysis of 19 cytologic features, we found that high nuclear cytoplasmic ratio, irregular nuclear membranes, and small cell clusters were most helpful in their distinction. Diagn. Cytopathol. 2016;44:561-567. © 2016 Wiley Periodicals, Inc.

Branchial Cleft Cyst as the Initial Impression of a Metastatic Thyroid Papillary Carcinoma: Two Case Reports

Solitary cystic neck lesions as the only presenting feature in adult patients may present diagnostic challenges as the aetiology may be malignant or non-malignant entities. Investigation is usually through radiology and tissue sampling. Subsequent diagnosis of malignancy requires thorough exploration for localization of primary tumour for complete treatment. We report 2 cases of solitary cystic neck lesion subsequently diagnosed as malignancy. First case is a 70-year-old man presented clinically with left branchial cyst. Excision of the cyst revealed papillary thyroid carcinoma. He underwent total thyroidectomy, central and left neck dissection despite no obvious nodule on physical examination or ultrasound. Histologically, no tumour was found on the thyroid or lymph node specimen. The second case is a 48-year-old man presented with painless right neck swelling. Excision showed squamous cell carcinoma arising in a right branchial cyst. Extensive examination did not show any other mass within the head and neck region. However, one year later his right neck swelling recurred. Histological examination confirmed metastatic squamous cell carcinoma to the neck lymph node. He underwent bilateral tonsillectomy and modified radical neck dissection following the finding of occult malignancy. Primary tumour was identified at the tonsil. Malignant cystic neck lesions are not uncommon. Solitary, painless lateral neck cyst in an adult warrant careful and detailed work-up. Aspiration of lateral neck cyst is an effective primary investigation tool prior to embarking on more costly or invasive examination.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S9

IntroductionBranchial cleft cysts (BCC) are congenital cystic lesions of the lateral neck resulting from incomplete obliteration of the branchial clefts during embryogenesis. They are typically located anterior to the sternocleidomastoid muscle and are benign in nature. Papillary thyroid carcinoma (PTC) is the most common histological subtype of thyroid malignancies. Due to its propensity for cervical lymph node metastasis, it may mimic cystic lesions of the lateral neck, posing a diagnostic challenge in adults.Clinical CaseA 35-year-old female presented to the otolaryngology clinic with a painless neck swelling. Physical examination revealed a 3cm lesion in the right level IV region. There was no history of autoimmune thyroid disease, radiotherapy, or family history of thyroid cancer. Ultrasonography showed a normal sized thyroid with a 10×8 mm isohyperechoic nodule in the left lobe, with a regular margin, halo, and peripheral vascularization. In addition, a 30×15 mm anechoic cystic lesion was detected anterior to the sternocleidomastoid muscle and was initially considered as BCC. Fine-needle aspiration biopsy was nondiagnostic. Contrast-enhanced MRI revealed a 17×22 mm well-circumscribed, dense-content lesion, again suggestive of BCC. The patient underwent surgery with this presumptive diagnosis. Histopathological examination demonstrated papillary thyroid carcinoma invasion in the cyst wall, consistent with metastatic PTC. Following multidisciplinary tumor board evaluation, total thyroidectomy with bilateral central and right lateral neck dissection was performed. Postoperative pathology revealed a 0.8 cm oncocytic variant papillary microcarcinoma in the right lobe, with capsular invasion within 0.1 cm, and metastasis in three central lymph nodes. The patient was classified as high-risk and received 150 mCi of radioactive iodine (RAI). Post-therapy I-131 scintigraphy showed uptake confined to the thyroid bed, with no evidence of distant metastasis. During follow-up, TSH was suppressed below 0.1 mIU/L. Stimulated thyroglobulin was 7 µg/L with negative anti-Tg antibodies. At the latest follow-up, thyroglobulin was 0.6 µg/L, consistent with a biochemical indeterminate response.Cystic lymph node metastases of PTC can easily be misdiagnosed as BCC, especially in adults. Several cases in the literature have reported lesions initially excised under the presumptive diagnosis of BCC that were later confirmed as metastatic PTC. Therefore, in adult patients with lateral cervical cystic lesions, careful evaluation is essential, and suspicious radiologic findings must be followed by thorough histopathological analysis. Clinical history, imaging features, and, when necessary, repeat biopsies are crucial for accurate diagnosis.ConclusionPapillary thyroid carcinoma can present as cystic lymph node metastases mimicking branchial cleft cysts; thus, this diagnosis must be considered in adults with lateral neck masses

Mutations of the p53 tumor suppressor gene, with consequent nuclear p53 protein accumulation, are among the most common genetic abnormalities in human cancers. The purpose of this study was to determine the utility of p53 immunostaining as an adjunct to the diagnosis of malignancy in fine-needle aspirations of squamous lesions of the neck. Using a monoclonal antibody to the p53 protein and a standard avidin-biotin complex technique, immunostaining was performed on paraffin-embedded cell blocks of 20 cases with the following cytologic diagnoses: (1) metastatic squamous cell carcinoma (SCC) (7 cases); (2) atypical squamous cells, SCC cannot be excluded (7 cases); and (3) cytologic findings consistent with branchial cleft cyst (6 cases). Tissue or clinical follow-up was available in all cases. Five (71%) of 7 cases with an unequivocal cytologic diagnosis of metastatic SCC were positive for p53 protein. Tissue follow-up confirmed metastatic SCC in all of these 7 cases. Of the 7 cases with cytologic diagnosis of atypical squamous cells, 2 were negative and 5 (71%) were positive for p53 protein. Subsequent excisional biopsies in these cases revealed metastatic SCC (6 cases) and branchial cleft cyst (1 case). The squamous cells in all 5 cases with cytologic findings consistent with branchial cleft cyst were negative for p53 protein; tissue follow-up confirmed the diagnoses of branchial cleft cyst in 4 cases. In the remaining 2 cases excision was not performed, as the cystic lesion was completely decompressed and, clinically, no recurrences were identified at 14 and 8 months of follow-up. Our findings suggest that p53 immunostaining is helpful in differentiating benign and malignant squamous lesions. While negative staining for p53 does not exclude malignancy, positive immunostaining may aid in accurate fine-needle aspiration diagnosis of malignancy in cytomorphologically equivocal squamous lesions of the neck.

We investigated p16(INK4A) expression in branchial cleft cysts and its utility in distinguishing branchial cleft cysts from metastatic head and neck squamous cell carcinomas (SCCs) in fine-needle aspiration biopsies (FNABs). A study set comprising 41 resections (15 SCC and 26 branchial cleft cysts) and a test set of 15 FNABs (11 SCC and 4 branchial cleft cysts) were analyzed with p16(INK4A) immunohistochemistry and human papillomavirus (HPV) polymerase chain reaction (PCR)/pyrosequencing. Cases with discrepant p16(INK4A) and PCR/pyrosequencing results were further evaluated with HPV in situ hybridization (ISH). SCCs were divided into keratinizing SCC and nonkeratinizing SCC groups and site of origin. Metastatic oropharyngeal nonkeratinizing SCC in the study set exhibited diffuse, strong p16(INK4A) (7 of 7) and HPV16 DNA positivity (6 of 6), while keratinizing SCC from the larynx and oral cavity was negative for p16(INK4A). p16(INK4A) reactivity in the branchial cleft cyst study set was characterized by focal, strong staining (6 of 21) involving the superficial squamous epithelium. HPV DNA was identified in 7 of 19 branchial cleft cyst study set cases by PCR/pyrosequencing, but these cases were negative by HPV ISH. In the test set, oropharyngeal nonkeratinizing SCC exhibited diffuse, strong p16(INK4A) (3 of 3) and HPV16 DNA (2 of 2), while metastatic keratinizing SCC was negative for p16(INK4A) and HPV DNA. All 4 FNABs of branchial cleft cysts were negative for p16(INK4A). Diffuse, strong p16(INK4A) correlated with oropharyngeal origin (P=.001) and nonkeratinizing morphology (P=.0001). Branchial cleft cysts can exhibit focal strong reactivity limited to the superficial squamous epithelium and glandular epithelium. Although p16(INK4A) immunohistochemistry may be helpful in distinguishing oropharyngeal nonkeratinizing SCC from branchial cleft cysts in FNAB specimens, it is not helpful in cases of keratinizing SCC because these cases are typically negative for p16(INK4A).

Cystic change in metastatic lymph nodes of papillary thyroid carcinoma (PTC) is a diagnostic challenge for fine needle aspiration (FNA) because of the scant cellularity. The aim of this study was to evaluate the measurement of thyroglobulin in fine needle aspirate (Tg-FNA) for detecting metastatic PTC in patients with cystic neck lesions and to validate the optimal cutoff value of Tg-FNA. A total of 75 FNA specimens of cystic lesions were identified, including 40 of metastatic PTC. Predetermined threshold levels of 0.04 (minimum detection level), 0.9, 10.0, and 77.0 ng/mL (maximum normal serum-Tg level) were used to evaluate the diagnostic accuracy of Tg-FNA for metastatic PTC detection. The areas under the receiver operating characteristic curve for diagnosing metastatic PTC of Tg-FNA values of 0.04, 0.9, 10.0, and 77.0 ng/mL were 0.5 (95% confidence interval [CI], 0.382–0.618), 0.645 (95% CI, 0.526–0.752), 0.945 (95% CI, 0.866–0.984), and 0.973 (95% CI, 0.907–0.996), respectively. With a cutoff value of 77.0 ng/mL, the combination of Tg-FNA and FNA cytology showed superior diagnostic power (97.5% sensitivity and 100% specificity) compared to FNA cytology alone (80% sensitivity and 100% specificity). We recommend a Tg-FNA cutoff of 77.0 ng/mL, the maximum normal serum-Tg level, for cystic neck lesions.