Diagnostic value of GLUT-1 immunoreactivity to distinguish benign from malignant cystic squamous lesions of the head and neck in fine-needle aspiration biopsy material

The distinction of cystic squamous-cell carcinoma (SCC) from benign cystic squamous lesions (BCSLs) of the head and neck can be problematic on fine-needle aspiration biopsy (FNAB) material, particularly when BCSLs display epithelial reactive atypia or when SCC is well differentiated. Glucose transporter 1 (GLUT-1), a facilitative cell surface glucose transport protein, is aberrantly expressed in many cancers including oral and hypopharyngeal SCC. We evaluated the expression of GLUT-1 by immunochemistry on FNAB material to determine its value in distinguishing cystic SCC from BCSL of the head and neck. A 5-yr retrospective review of all head and neck cystic squamous lesions having FNAB specimens with cell block material, radiological studies, and histological confirmation was performed at our institution. Cell block material from 24 cystic squamous lesions, including 8 (33%) BCSL (7 branchial cleft cysts and 1 thyroglossal duct cyst[TDC]) and 16 (67%) metastatic SCCs with cystic/liquefactive degeneration, was retrieved and immunostained with anti-GLUT-1. GLUT-1 expression was considered positive when at least 10% of squamous cells exhibited distinct cell membrane reactivity. Positive GLUT-1 immunostaining was detected in all 16 SCCs and in none of the 8 BCSLs. In the carcinoma cases, the majority of malignant cells exhibited GLUT-1 reactivity; only a minor population of well-differentiated SCC cells displaying keratinization and arranged as squamous pearls did not express GLUT-1. GLUT-1 expression in cell block material can help to distinguish cystic SCCs from BCSLs of the head and neck. In conjunction with clinical and radiological correlation, GLUT-1 immunoreactivity can be an important diagnostic aid when the cytological findings are ambiguous.     

Sources of diagnostic error in the fine-needle aspiration diagnosis of Warthin's tumor and clues to a correct diagnosis

Squamous metaplasia and cystic degeneration in Warthin's tumor (WT) are not uncommon. A recent case of WT misdiagnosed as metastatic squamous carcinoma with cystic change prompted us to review our experience with fine-needle aspiration (FNA) of WT, with special attention given to potential sources of diagnostic pitfalls. Aspirations from 16 cases of histologically confirmed WT were retrospectively evaluated for cellularity, cell composition, and background. The FNA review diagnosis was compared with the previous FNA and corresponding tissue findings. All tumors presented in the parotid gland. The initial cytologic diagnoses were: WT in 13 cases, oncocytoma vs. low-grade mucoepidermoid carcinoma in 1, squamous carcinoma vs. branchial cleft cyst in 1, and squamous carcinoma in 1. On review, 13 cases (81%) showed typical features associated with WT: Moderate to abundant oncocytic epithelium, lymphoid stroma, background debris, and mild squamous metaplasia. In the remaining cases, one lacked a lymphoid stroma and could not be further classified (initially called “oncocytoma vs. low-grade mucoepidermoid carcinoma”). The other 2 cases contained moderate to abundant atypical squamous cells and extensive necrotic/mucoid debris, and review diagnoses were consistent with the initial cytologic diagnoses (squamous carcinoma in one, and branchial cleft cyst vs. squamous carcinoma in the other). In our series, typical features of WT were seen in 81% of cases. Atypical features are largely present as individual metaplastic squamous cells. Diagnostic errors are caused by a lack of typical features and the presence of individual atypical squamous cells in a necrotic background mimicking carcinoma. An awareness of the morphologic variation present on cytologic preparations and correlation with clinical findings should prevent erroneous interpretation in the FNA setting. Diagn. Cytopathol. 1997;17:230–234. © 1997 Wiley-Liss, Inc.     

Cytokeratin7 expression in histologic and cytologic specimens of cystic neck metastasis from HPV positive squamous cell carcinoma of the tonsil: A case report

The majority of cystic squamous cell carcinomas (SCCs) of the neck have been shown to be metastatic tumors from tonsillar SCCs associated with high‐risk human papillomavirus (HR HPV). Recent studies have demonstrated cytokeratin (CK)7 involvement in the development of HPV positive SCC, but no report has been issued on its simultaneous expression in primary tonsillar and metastatic tumor with cystic change. We present a case of HPV positive tonsillar SCC of a 42‐year‐old male that initially manifested as a cystic neck mass expressing CK7, CK19, and p16 in primary and metastatic tumors. Immunohistochemical examination revealed diffuse CK19 and p16 expression, and patchy CK7 expression in the solid components of primary and metastatic tumors. However, in cystic components of metastatic tumors the expression of CK7 and CK19 was preserved but p16 expression was absent, which was consistent with immunocytochemical findings of fine‐needle aspirates from cystic neck mass. In immunocytochemistry performed on aspirates of a branchial cleft cyst for the comparison of cystic SCC and benign cyst, CK19 staining was positive but CK7 and p16 staining was negative. These results suggest that CK7 immunocytochemistry on aspirated material from cystic neck mass may be a useful adjunct for distinguishing cystic metastasis of tonsillar SCC from branchial cleft cyst, although a larger scale study would be required.     

Squamous cells in needle aspirates of subcutaneous lesions: a diagnostic problem

Analysis of 1,000 cases of fine-needle aspiration biopsies of subcutaneous lesions revealed 430 cases diagnosed as malignant. Squamous cell carcinoma represented 37% of the malignant neoplasms, and many of these cases were highly differentiated tumors. Although the presence of keratinized squamous cells in superficial aspirates is strongly suggestive of squamous cell carcinoma, other lesions may produce atypical squamous cells on aspiration biopsy and should be considered in the differential diagnosis. These include acanthotic ameloblastomas, metaplastic adenocarcinomas and Warthin's tumors, branchial cleft cysts, odontogenic keratocysts, and epidermal inclusion cysts. Two-needle aspirates from these cases were incorrectly interpreted as squamous cell carcinoma. The cytologic and some of the histologic characteristics of these lesions that may pose a diagnostic problem are presented. Careful evaluation of nuclear and cytoplasmic features, cellular background, clinical findings, and history is essential to avoid a false positive diagnosis of squamous cell carcinoma.     

Sun-exposure- and aging-dependent p53 protein accumulation results in growth advantage for tumour cells in carcinogenesis of nonmelanocytic skin cancer

 Three hundred and sixteen patients with nonmelanocytic skin cancer, including 46 cases of Bowen’s disease (BOD), 134 cases of squamous cell carcinoma (SCC), and 136 cases of basal cell carcinoma (BCC), were examined immunohistochemically using monoclonal antibody DO-7 to assess p53 protein accumulation related to sun exposure and ageing, and growth and differentiation of skin cancer and its precursors. The rates of p53 immunostaining of BOD, SCC and BCC were 80.4%, 76.1% and 70.6%, respectively. p53-positive cells were present not only in cancer nests, but also in dysplastic and even morphologically normal epidermis adjoining cancers. Sun exposure was statistically correlated with the p53 immunostaining scores in morphologically normal epidermis of the three skin cancers and in cancer nests of SCC and BCC. The positivity and score of p53 protein often differed significantly among the three types of cancer, especially in regions of dysplasia. Interestingly, differentiation of SCC was correlated with individual p53 scores for dysplasia and cancer nests, especially for dysplasia. BOD, as the precursor of SCC, demonstrated the strongest p53 expression. Furthermore, 12.3% cases with p53 negative cancer nests showed p53-positive reaction in dysplasia and in morphologically normal epidermis. It seems that the accumulation of p53 protein plays a part in precancerous lesions and in the genesis of more highly differentiated types of skin cancer and affects mainly the growth of tumour cells rather than their differentiation. For BCC, however, age was significantly related to p53 expression. Our findings suggest that overexpression of p53 in normal skin and cancer nests of SCC and BCC is significantly related to sun exposure, that the expression of p53 in BCC is an age-dependent process, and that the early accumulation of p53 protein may be a useful predictor for the detection of nonmelanocytic skin cancer. Received: 7 July 1998 / Accepted: 5 November 1998     

A case of second branchial cleft cyst with oropharyngeal presentation

Second branchial cleft cysts are the most common type of branchial abnormalities and usually found high in the neck. Oropharyngeal presence of branchial cleft cyst is very rare. We report a case of oropharyngeal branchial cleft cyst in 2-yr-old girl with about 1 x 1 cm sized cystic mass, which had not any specific symptom. It was removed completely under impression of mucocele and did not have tract-like structure. However, cyst had a squamous epithelium-lined wall with lymphoid aggregation in histopathologic study, which was characteristic finding of branchial cleft cyst. Patient discharged without any complication and there was no evidence of recurrence for 18 months follow-up. We review reported oropharyngeal or nasopharyngeal presentation of these cases in English literature and embryological explanation.     

Malignant first branchial cleft cysts presented as submandibular abscesses in fine-needle aspiration: report of three cases and review of literature

Malignant branchial cleft cyst is a rare entity. To the best of our knowledge, there have been one case of malignant first branchial cleft cyst and 13 cases of malignant second branchial cleft cysts in the literature that fulfill Khafif's modified criteria since 1982. We have encountered three such cases, presenting as unilateral submandibular abscesses, refractory to antibiotics, from men of 52, 53, and 61 years of age. Fine-needle aspiration was reported as "abscess" in the first case, "atypical squamous cystic lesion" in the second case, and "atypical first branchial cleft cyst" in the third case. Histopathology showed Type II malignant first branchial cleft cysts with in situ squamous-cell carcinoma in one patient and in situ and invasive squamous-cell carcinoma in the other two patients. Patients are alive and disease-free 3-4.5 years post-surgery and -radiation. Awareness of this extremely rare entity can potentially avoid underdiagnosis by the cytopathologist and overtreatment by the surgeons.     

Metastatic squamous cell carcinoma of the gingiva appearing as a solitary branchial cyst carcinoma: diagnostic role of PET/CT

We herein present a case of a left cervical cystic mass, for which the initial pathological diagnosis was branchial cleft cyst carcinoma (following complete mass excision). Thorough postoperative examinations, including with FDG positron emission tomography/computed tomography (PET/CT), revealed a primary tumor in the retromolar region of the left mandible. A 52-year-old female presented with a 2-month history of a painless, progressively enlarged left-sided neck mass. Fine-needle aspiration biopsy suggested a branchial cleft cyst. Physical examination revealed a 3 × 3-cm smooth, tender mass in the upper-left neck and anterior border of the sternocleidomastoid muscle. Examination using nasendoscopy and a strobolaryngoscope revealed no abnormalities of the nasal cavity, nasopharynx, oropharynx, hypopharynx or larynx. MRI of the neck revealed a solitary, round, cystic mass under the left parotid gland. The mass was excised completely. Pathologic results indicated a branchial cleft cyst carcinoma. According to the diagnostic criteria for a branchial cleft cystic carcinoma, PET/CT was performed to detect the occult primary site. PET/CT revealed high FDG uptake in the tooth root of the left mandible. Frozen sections of the mass were indicative of moderate, differentiated squamous cell carcinoma. The carcinoma in the retromolar region of the left mandible was locally excised under general anesthesia. A partial left maxillectomy, partial mandibulectomy, and left radical neck dissection were performed. The patient received postoperative concurrent chemoradiotherapy, and was disease-free at the 8-month follow-up. True branchial cleft cyst carcinoma is rare: once diagnosed, it should be distinguished from metastatic cystic cervical lymph and occult primary carcinoma. FDG PET/CT is useful in the identification of occult primary tumor.     

Cytomorphologic diagnosis and HPV testing of metastatic and primary oropharyngeal squamous cell carcinomas: a review and summary of the literature

A significant proportion of squamous cell carcinomas (SCC) of the oropharynx are associated with high-risk human papillomavirus (HPV). These HPV-related carcinomas are prognostically and therapeutically different from traditional SCC of the head and neck. Cervical metastases from head and neck primary SCC are frequently investigated by fine-needle aspiration (FNA). HPV testing of cytologic samples from these lesions would potentially simplify diagnosis and therapeutic planning. This review summarizes current methodologies for HPV testing of FNA specimens and the role of HPV typing in diagnosis, prediction of prognosis, and selection of therapy.     

Primary pure squamous cell carcinoma of the breast diagnosed by fine-needle aspiration cytology: a case study using liquid-based cytology

Pure primary squamous cell carcinoma (SCC) is an extremely rare type of breast tumor. We report one of such cases in a 32-year-old woman, diagnosed by fine-needle aspiration cytology (FNAC). Aspiration smears were characterized by squamous cells, both isolated and in aggregates, at various stages of maturation. The tumor was excised, and the histologic sections confirmed the cytologic diagnosis. Pure primary SCC of the breast has a distinctive cytomorphologic appearance, and diagnosis of this tumor by FNAC is possible. For its diagnosis, the exclusion of SCC of local cutaneous structures and metastasis of distant squamous carcinoma are mandatory.     

The cytology of pediatric masses: a differential diagnostic approach.

In the United States, fine-needle aspiration biopsy (FNAB) and other cytodiagnostic methods have been underutilized in the evaluation of masses in the pediatric age group. Cytopathologists and cytotechnologists are therefore relatively unfamiliar with the cellular features of lesions that occur in children. On the basis of the cytologic findings from 64 pediatric cases, including 56 FNABs and 8 intra-operative imprints, a differential diagnostic approach to lesions in this age group is presented. The majority of cases can be placed into 1 of 5 cytomorphologic categories: (1) round-cell pattern, (2) mixed inflammatory pattern, (3) spindle-cell pattern, (4) epithelial pattern, and (5) cystic pattern. Once a cytomorphologic category is determined, evaluation for unique cellular features, special studies, and clinical correlation allows a specific diagnosis to be made in most cases. Pitfalls in pediatric cytopathology are illustrated by discussion of the following cases: a renal Burkitt's lymphoma mimicking a Wilms' tumor, a traumatic neuroma masquerading as a recurrent malignant schwannoma, Langerhans-cell histiocytosis resembling granulomatous inflammation, and a cystic granuloma that mimicked a branchial cleft cyst. Consideration of these problems and use of the recommended diagnostic approach will aid in interpretation in this difficult area.     

Diagnosis of foregut and tailgut cysts by endosonographically guided fine-needle aspiration

Foregut, hindgut, and tailgut cysts are uncommon developmental anomalies. Clinical and radiological diagnosis can present many challenges, especially in adult patients or when the lesions are in unique locations. Thus, diagnosis has traditionally been provided upon surgical resection. We describe the diagnoses of a gastric foregut cyst and a retrorectal tailgut cyst by endosonographically guided fine-needle aspiration in two adults. The common cytologic features of the specimens are ciliated epithelial cells, proteinaceous material with degenerated debris, histiocytes, and benign appearing epithelium of squamous and/or gastrointestinal type that lack cytologic atypia. The identification of ciliated columnar cells is the key finding. Cytologic diagnosis via endosonographically guided fine-needle aspiration of foregut/hindgut cyst is accurate and less traumatic than surgical biopsies.     

Accuracy of fine-needle aspiration of thyroid

CONTEXT: Fine-needle aspiration has become an accepted and cost-effective procedure for rapid diagnosis of thyroid lesions. The routine use of fine-needle aspiration has reduced the rate of unnecessary surgery for thyroid nodules. OBJECTIVES: To determine the accuracy of fine-needle aspiration biopsy diagnosis and to discuss the possible pitfalls. Design, Setting, and Participants.-Reports of 6226 fine-needle aspiration biopsies of the thyroid performed during a period of 16 years (1982-1998) were reviewed. Computerized reports of the fine-needle aspiration biopsies were sent to the physicians who performed the procedures, and clinical follow-up information regarding the patients was requested. Twenty-four clinicians participated in the study. Histologic diagnoses were available for 354 cases. The cytopathologic diagnoses were correlated with the histologic findings or clinical outcomes. RESULTS: The cytologic diagnoses were as follows: 210 (3.4%) malignant, 450 (7.2%) suspicious, 3731 (60%) benign, and 1845 (29.5%) unsatisfactory. Most of the cases with negative or unsatisfactory aspirates were followed clinically or by repeat fine-needle aspiration. We identified 11 false-negative and 7 false-positive diagnoses. For aspirates considered sufficient for diagnosis, the sensitivity and specificity levels were 93% and 96%, respectively. CONCLUSIONS: Fine-needle aspiration of the thyroid gland is highly accurate and has a low rate of false-negative and false-positive diagnoses. The major diagnostic problems are caused by diagnosis using a marginally adequate specimen, diagnosis of malignancy based on just 1 or 2 atypical cytologic features, or overlapping cytologic features of follicular neoplasm with those of follicular variant of papillary carcinoma.     

Needle biopsy of the adrenal gland: Retrospective review of 54 cases

A retrospective review of 54 cases of adrenal gland needle biopsy in 53 patients is presented. The cases included 43 fine-needle aspirations (FNA), six core-needle biopsies, and five cases in which both types of needle biopsy were done. Clinical or histologic follow-up was available in 28 of the 36 specimens deemed adequate for evaluation. Metastatic malignancies represented the largest group of cases (19), with lung being the most common primary site (8). The series included four cases of metastatic hepatocellular carcinoma. Probable adrenocortical adenoma was the next most common diagnosis (12 cases). Cases causing diagnostic confusion included a case of metastatic well-differentiated hepatocellular carcinoma which was initially confused with an adrenocortical adenoma and a probable adrenocortical adenoma which was mistaken for a metastatic small round cell malignancy. (This case is unproved because of lack of clinical or histologic follow-up). By evaluating only those cases with histologic confirmation or clinical follow-up greater than one year, the sensitivity of needle biopsy for the presence of malignancy was 95% and the specificity was 100%. The cytologic findings are described with attention to the potential problem of confusing primary adrenocortical neoplasms with metastases from hepatocellular carcinoma. Diagn Cytopathol 1996;14:126–134. © 1996 Wiley-Liss, Inc.     

p53 and erbB-2 are not associated in matched cases of primary and metastatic ovarian carcinomas

Ovarian cancer has a high mortality rate largely due to the limited number of ovarian carcinomas detected at an early stage. Understanding the molecular changes occurring during the progression of ovarian carcinoma would aid in the development of therapies that may inhibit or target metastasis. Primary and metastatic lesions from 54 and 40 patients with advanced ovarian carcinoma, respectively (including matched primary and metastatic lesions from 30 patients) were evaluated for nuclear accumulation of p53 (clone BP53-12-1) and cytoplasmic and membranous immunostaining of p185 erbB-2 (clone 3B5) by immunohistochemistry. No differences in the immunostaining of p53 and p185erbB-2 (cytoplasm or membrane) were observed between primary and metastatic lesions of the matched cases. Similarly, no differences in the proportion of positive cases of p53 between primary and metastatic lesions of the matched cases was observed. Thus, novel therapies that target p53 or p185erbB-2 can utilize specimens from either primary or metastatic lesions to characterize these targets prior to therapy. Spearman correlations between p53 and p185erbB-2 (cytoplasm or membrane) immunohistochemistry scores were insignificant for the matched cases, all primary lesions, and all metastatic lesions. Also, no significant associations occurred between nuclear accumulation of p53 (positive versus negative) and phenotypic expression of p185erbB-2 (cytoplasm or membrane) immunostaining scores for the matched cases, all primary lesions, and all metastatic lesions. Thus, the nuclear accumulation of p53 and immunostaining of p185erbB-2 in the cytoplasm or on the cellular membranes are independent.     

Malignant branchiogenic cyst--fact or fiction?

A case of a cystic metastasis of squamous cell carcinoma of palatine tonsil in a 54-year-old male is reported, clinically presenting as a branchiogenic cyst. The grade of differentiation of the squamous cell epithelium lining the cyst was very variable: in some areas it was extremely well differentiated, thus resembling common benign branchial cleft cyst; transition to dysplastic areas with features of carcinoma in situ was visible and finally, in one small focus, invasion of the epithelial structures into the lymphoid tissue was observed. Despite its metastatic nature, the tumor fulfilled histological criteria of a so called malignant branchiogenic cyst (branchiogenic carcinoma). The authors discuss the existence of primary malignant branchiogenic cyst and the criteria necessary for its diagnosis.