BACKGROUND: Salivary gland lesions possess diagnostic challenges on fine-needle aspiration (FNA) material. They are relatively uncommon, yet present with a wide spectrum of cytomorphology. Herein, we review common salivary gland neoplasms, their cytomorphologic features, their diagnostic pitfalls, and ancillary studies helpful in achieving an accurate diagnosis.
CONCLUSIONS: There are many cytomorphologic overlaps between benign and malignant salivary gland entities. Moreover, metaplasia, cystic changes, and degenerative changes are common findings adding to diagnostic dilemmas. These complicating factors contribute to a minute risk of malignancy in salivary gland lesions that are interpreted as benign on FNA. In rare cases, even malignant salivary gland neoplasms are misinterpreted as benign on aspirated material due to the many cytomorphologic overlaps. For example, benign and malignant neoplasms containing stroma such as myoepithelioma and adenoid cystic carcinoma may be misinterpreted as pleomorphic adenoma. Moreover, diagnosis of salivary gland neoplasms with basal cell features can be confusing on FNA materials; for example, basal cell adenoma can be misinterpreted as adenoid cystic carcinoma. Mucoepidermoid carcinomas have many different appearances on aspirated material due to variable amounts of mucin, degree of nuclear atypia, cellular content, and squamous metaplasia. Acinic cell carcinoma exhibits large cells with abundant cytoplasm on FNA, which can be mistaken for oncocytic cells in oncocytoma or Warthin tumor. Salivary duct carcinoma shows distinct features of malignancy and thus can be mistaken for secondary tumors involving the salivary glands or other malignant salivary gland tumors. The presence of tumor-associated lymphocytes is another underlying cause of misdiagnosis, especially when considering the differential diagnosis of an intraparotid lymph node. Ancillary studies such as immunohistochemistry and molecular studies are gaining more attention to be utilized on FNA cases. PLAG1 immunostaining, CD117, DOG1, mammaglobin, and androgen receptor (AR) are examples of commonly used immunostains in diagnosis of salivary gland lesions. MYB gene fusion, rearrangements of the MAML2 gene, and ERBB2/HER2 are examples of molecular alterations useful in diagnosis of salivary gland neoplasms. In conclusion, the aim of salivary gland cytology is to differentiate benign entities from the malignant ones and to prevent unnecessary aggressive treatments.
CONCLUSIONS: The diagnostic pitfalls are enormous in salivary gland cytology. Familiarity with cytomorphology of different entities and their cytomorphologic overlaps, and application of ancillary studies improves the diagnostic yield, patient management and prevents unnecessary aggressive procedures.

BACKGROUND: Papillary thyroid carcinoma accounts for the most common type of thyroid cancer of well-differentiated type. Papillary thyroid carcinoma is featured by biologically low-grade and less aggressive tumors with a survival rate of 10 years in most of the diagnosed cases. Papillary thyroid carcinoma can be presented with the involvement of cervical lymph nodes in about 50% of the patients, yet distant spread is very uncommon.
METHODS: Herein, we discuss a Saudi male patient in his early 50s with a history of papillary thyroid carcinoma who presented to the emergency department complaining of shortness of breath and a radiological finding of hydrothorax. Cytologic examination together with immune-histochemical staining and molecular studies of pleural effusion aspiration concluded the definitive diagnosis of metastatic papillary thyroid carcinoma in the pleural space.
CONCLUSIONS: Papillary thyroid carcinoma seldom causes metastatic niches in the pleural space; this is a rare clinical presentation, nevertheless, a differential diagnosis of thyroid metastasis needs to be excluded. A definitive diagnosis of metastatic papillary thyroid carcinoma can be made using clinical presentation, cytologic examination, immunohistochemical investigation, and molecular testing. The most common mutation found in papillary thyroid carcinoma cases is the V600E mutation found in the BRAF gene, yet these patients have a relatively low probability of cancer recurrence. Patients with papillary thyroid carcinoma who have the BRAF mutation frequently experience metastases and relapses of the disease after the cancer has progressed aggressively. To help with therapy planning and the introduction of BRAF inhibitors, genetic testing for BRAF mutation may therefore prove to be a useful tool, especially in cases of aggressive subtypes of TC.

BACKGROUND: Thyroid malignancy is one of the most common types of cancer in developed nations. Currently, fine-needle aspiration cytology (FNAC) is the most practical screening test for thyroid nodules. However, cytologically indeterminate samples comprise approximately 15%-30% of cases. These include cases classified as atypia of undetermined significance (AUS), follicular neoplasm (FN), and suspicious for malignancy (SFM). Indeterminate cases can be sent for molecular testing for more definitive classification to help guide management and prevent overtreatment of benign thyroid nodules. We conducted a retrospective review on molecular testing of indeterminate thyroid FNAC and reviewed subsequent histologic diagnoses in resection specimens to assess how molecular testing supported a diagnosis and its effect on clinical management of patients at our institution.
METHODS: A retrospective chart review was performed on all thyroid FNAC specimens, corresponding molecular testing, and subsequent surgical resection specimens over a 6-year period.
RESULTS: A total of 10,253 thyroid FNAC were performed in our hospital system during our study period, of which 10% (n = 1102/10,253) had indeterminate FNAC results. Molecular testing was performed in 16% (n = 178/1102) of indeterminate cytology cases. Genetic alterations were identified in 39% (n = 69/178) of the cases sent for molecular testing. The majority of cytologically indeterminate cases sent for molecular testing were follicular-patterned lesions and their corresponding resection specimens revealed mostly low grade follicular derived neoplasms (i.e., follicular adenoma, non-invasive follicular thyroid neoplasm with papillary-like nuclear features, and follicular variant of papillary thyroid carcinoma). Of the cases with identified genetic alterations, 75% (n = 52/69) were treated surgically. In cases with no genetic alterations identified, only 18% (n = 20/109) were treated surgically.
CONCLUSIONS: Molecular testing on cytologically indeterminate thyroid nodules can help provide a more accurate risk of malignancy assessment in patients with lesions that are difficult to diagnosis based solely on FNAC morphology. The types of genetic alterations identified in the resected thyroid lesions were consistent with what has been previously described in the literature. Additionally, we found that in the patients with indeterminate thyroid FNAC with adjunct molecular testing, more than half did not undergo surgical resection. This finding emphasizes the value of adding molecular testing in patients, particularly when attempting to reduce unnecessary surgical intervention.

BACKGROUND: The occurrence of extragonadal germ cell tumors (EGGCTs), either as primary tumors or metastatic disease, is rare. Forms of cytologic sampling, including fluid analysis, fine-needle aspiration, and/or small-core needle biopsy, have been shown to be reliable methods for the diagnosis of germ cell tumors. This study aims to investigate the utility of cytopathologic techniques in the diagnosis of EGGCTs at the authors\' institution.
METHODS: The laboratory information system was queried over a period of 10 years (2012-2022) to identify all cytology cases diagnosed on fluid cytology, FNA, and/or small-core biopsy as germ cell tumors in extragonadal locations. Patient demographics, tumor location, serum tumor marker levels, cytopathologic diagnosis, and follow-up surgical resection data were reviewed and correlated.
RESULTS: A total of 35 cases from 32 patients (all males) were identified. Thirty specimens contained satisfactory material for diagnosis (86%) and five were less than optimal for evaluation (14%). Despite this, all cases had clinically useful cytopathologic diagnoses. A total of 19 cytology cases (16 patients) had follow-up resection specimens available. Of these, 11 patients underwent preoperative chemotherapy. Nine patients showed no evidence of residual tumor and two showed histologic concordance. Of the five patients who did not have preoperative chemotherapy, all showed concordant histologic diagnoses.
CONCLUSIONS: Cytology can provide a reliable, accurate method for diagnosing EGGCTs. The practice of preoperative (neoadjuvant) chemotherapy places an extreme importance on the initial cytopathologic diagnosis because the majority of patients with follow-up resection in this series showed no residual tumor.

Introduction Endometrial aspiration cytology (EAC) is a noninvasive, rapid, and cost-effective procedure for diagnosing gynecological disorders. This study aimed to validate endometrial aspiration as a routine, safe, and efficient outpatient diagnostic procedure, correlating its findings with histopathology evaluations to facilitate early surgical planning for patients with abnormal uterine bleeding. Materials and methods This cross-sectional study involved patients of reproductive, menopausal, and postmenopausal age groups who presented with diverse gynecological concerns that required dilatation and curettage. Endometrial aspiration was performed using a Karman cannula (Angiplast Pvt. Ltd., Vatva, India), and the obtained material was prepared into smears and stained for evaluation. Sampling adequacy, the nature of glandular and stromal cells, phasing of the endometrium, and other abnormalities were assessed and correlated with histology to examine the diagnostic utility of endometrial cytology. Results EAC showed 90.66% sampling adequacy with the Karman cannula. The sensitivity of EAC for diagnosing benign and malignant conditions was 88.7% and 100%, respectively. Conditions including secretory endometrium, proliferative phase, tuberculous endometritis, and glandular hyperplasia were diagnosed using EAC and confirmed by histopathology. Six malignancies were successfully diagnosed on cytology smears, while challenges in differentiation and sampling errors were recognized as limitations of the technique. Conclusions This study established EAC as a highly sensitive, minimally invasive preliminary diagnostic tool for gynecological disorders, particularly effective in diagnosing malignancy. Despite certain limitations, the procedure\'s ease, cost-effectiveness, and safety underscore its potential for routine use by surgeons.

Aspirates of liver abscess are frequently encountered in routine practice and are often of a low index of suspicion. However, necrotic liver metastasis clinically and radiologically mimics liver abscesses, and malignant cells can be obscured in an inflammation-rich background on cytology. It is important to recognise malignant neoplasms in this scenario, in particular uncommon conditions such as metastatic mucosal melanoma.

Ectopic adrenal cortical tissue has been reported in several locations, most often involving the retroperitoneal fat close to the adrenal gland. The reported cases presenting adjacent or proximal to the stomach are rare and mostly diagnosed on histology. To our knowledge, the cytologic features of ectopic adrenal cortical tissue diagnosed on fine needle aspiration are not well documented in the cytology literature. We describe the cytologic features of ectopic adrenal cortex which initially presented on imaging study as an enlarged gastrohepatic ligament \"lymph node\" on a patient with gastric signet ring cell carcinoma. The aspirates showed small clusters and cords of uniform cells with abundant vacuolated to densely compact cytoplasm, occasionally stripped nuclei, and delicate frayed cytoplasmic membranes dispersed in a bubbly, vacuolated background. Immunohistochemical stains performed on the corresponding cell block showed these cells were positive for SF-1 and negative for PAX 8. The corresponding biopsy showed similar findings in addition to immunoreactivity to inhibin. Because the cytologic features of ectopic adrenal cortical tissue especially on unusual sites could easily mimic malignant neoplasms, familiarity with the cytologic features in conjunction with immunohistochemical stains are key in arriving at the correct diagnosis and avoiding misdiagnosis.

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Anal malignancies are rare, and of these squamous cell carcinoma and basaloid squamous cell carcinoma are the most common types. Anal basaloid squamous carcinoma (BSC) can show a variety of patterns including unusual variants with cribriform areas resembling adenoid cystic carcinoma (ACC). BSC is reported more frequently in elderly females. Although the histopathology of BSC is characteristic, its cytomorphology is rarely described in the anorectal region. Due to overlapping morphological features, it is challenging to distinguish between ACC and BSC. Immunohistochemistry (IHC) is mandatory for this distinction and definite diagnosis, as it is a highly aggressive tumor with a tendency for distant metastasis. An interesting and rare case of BSC with ACC-pattern arising in the anal canal with liver metastasis in a middle-aged male is reported here. The aim is to highlight its cytological features, correlation with histology, IHC and its differential diagnoses.

UNASSIGNED: Endobronchial ultrasound (EBUS)-guided fine-needle aspiration cytology (FNAC) is recommended for diagnosing bronchial neoplasms and evaluating mediastinal lymph nodes. However, it may not be possible to subtype or definitely categorize many bronchial neoplasms on FNAC smears alone. Obtaining adequate diagnostic material is often a problem. In such cases, cell blocks made from FNAC material may serve as a useful adjunct. Aim: To study the value and limitations of cell blocks in adding diagnostic information to EBUS guided FNAC smears.
UNASSIGNED: One hundred and eighty-five cases of EBUS guided FNAC having concomitant cell blocks were reviewed. The cases were evaluated for the extent of adequacy, of definite benign/malignant categorization and of definite subtyping in malignant tumors in these cases. The proportion of cases in which cell blocks added information to FNAC smears alone for the above parameters were calculated.
UNASSIGNED: Cell blocks provided additional information in 31 out of 185 cases. Cell blocks were necessary for subtyping 24/59 malignant tumors, definite categorization into benign and malignant in 10/140 adequate samples, and increasing adequacy in 6/185 total samples. A total of 45 samples were inadequate in spite of adding information from cell blocks to smears.
UNASSIGNED: Cell blocks added clinically significant information to EBUS guided FNAC and should be used routinely. To make it more useful, alternative methods of cell block preparation (including proprietary methods) may be evaluated.