Fine-needle aspiration biopsy of axillary lymph nodes: A reliable diagnostic tool for breast cancer staging.

BACKGROUND: Pathologic evaluation of sentinel lymph node biopsy (SLNB) samples is crucial for axillary staging in patients newly diagnosed with breast cancer. Patients with pathologic evidence of nodal metastasis scheduled for upfront surgery typically also undergo axillary lymph node dissection (ALND). Although SLNB is the gold standard method for detecting nodal metastasis, axillary lymph node fine-needle aspiration biopsy (FNAB) utility has not been thoroughly explored. METHODS: Ultrasound-guided axillary lymph node FNAB samples along with concurrent ipsilateral breast tissue samples were searched and reviewed. The control group included histologic findings of axillary dissection or intraoperative SLNB results. RESULTS: A total of 354 axillary lymph node FNAB samples with matched histology were included. Of these, 187 (52.8%) were positive for metastatic carcinoma of breast origin; 143 (40.4%) were negative for metastasis; 12 (3.4%) showed atypical cells; six (1.7%) were suspicious for metastasis; and six (1.7%) were nondiagnostic because of a lack of lymphoid tissue and malignant cells. Of the 143 negative FNAB samples, 22 (15.4%) were positive on either intraoperative SLNB or ALND. When only the positive and negative FNAB samples were accounted for (n = 330; 93.2%), overall diagnostic sensitivity and specificity were 89.4% and 99.2%, respectively. CONCLUSIONS: Although axillary SLNB is the standard procedure for detecting nodal metastasis of breast origin, axillary lymph node FNAB appears to be a suitable alternative in a significant proportion of patients. A standard SLNB should be performed in cases of negative axillary lymph node FNAB findings, particularly nodes with abnormal imaging findings.

Prevalence of Human Papillomavirus Infection and Cervical Abnormalities among Women Attending a Tertiary Care Center in Saudi Arabia over 2 Years.

Human papillomavirus (HPV) genotype distribution varies according to the assessment method and the population targeted. This study aimed to assess HPV infection prevalence in women aged 23 to 82 with abnormal cytology attending King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, using retrospective data collected from January 2021 to December 2022. Cytological distribution included 155 samples of atypical squamous cells of undetermined significance (ASCUS) (n = 83), low-grade squamous intraepithelial lesion (LSIL) (n = 46), high-grade squamous intraepithelial lesion (HSIL) (n = 14), atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) (n = 10), and squamous cell carcinoma (SCC) (n = 2). All samples were submitted to HPV detection and genotyping using Xpert HPV assay specimens. The most prevalent epithelial abnormalities were ASCUS (53.50%). Positive HPV infection results were observed in 52.9% of the samples. The highest prevalence of HPV genotypes, accounting for 31%, was attributed to the other high-risk genotypes, including 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, and 68, followed by high-risk genotype 16, which counted in 11.60% of cases. Individuals who tested positive for HPV 16 were at a high risk of ASC-H, HSIL, and LSIL. Those testing positive for HPV 18-45 exhibited an elevated risk of LSIL, and those with positive results for other high-risk HPV genotypes were at an increased risk of ASCUS and LSIL, suggesting a low oncogenic potential. The results suggest that the percentage of association between samples with abnormal cervical presentation and negative high-risk HPV diagnosis is noticeably increasing. This underscores the need for effective screening programs and an understanding of the impact of specific HPV genotypes on cervical abnormalities.

Anaplastic thyroid cancer: Pathogenesis, prognostic factors and genetic landscape (Review).

Anaplastic thyroid cancer (ATC) is a rare and aggressive form of thyroid malignancy, presenting significant challenges in diagnosis and treatment. The rarity of this cancer and its aggressive nature make an accurate diagnosis difficult, requiring a multidisciplinary approach and various imaging techniques. Treatment involves a personalized multimodal approach, including surgery, adjuvant therapies and risk stratification. Prognostic factors such as age, tumor characteristics and genetic alterations play a crucial role in determining patient outcomes. Despite advancements, gaps remain in understanding the underlying mechanisms of the disease and establishing standardized treatment guidelines. Further research, collaborative efforts and multicenter studies are necessary to improve diagnostic accuracy, develop targeted therapies and biomarkers, and enhance the long-term management. The present review provides a comprehensive overview of ATC, discussing its clinical manifestations, diagnostic approaches, treatment options, prognostic factors and genetic landscape.

Revisiting the cytomorphological features of poorly differentiated thyroid carcinoma: a comparative analysis with indeterminate thyroid fine-needle aspiration samples.

INTRODUCTION: Poorly differentiated thyroid carcinoma (PDTC) is an uncommon high-grade carcinoma of follicular cell origin that is usually overlooked on preoperative fine-needle aspiration (FNA) due to its rarity and cytomorphological overlap with follicular-patterned neoplasms. Definitive diagnosis of PDTC usually requires histologic examination of the resected thyroid tumor. Herein, we describe the cytological and architectural findings of histologically confirmed PDTC cases. MATERIALS AND METHODS: A search for all thyroid FNAs with a corresponding surgical diagnosis of PDTC was performed. Surgical diagnoses were reviewed and confirmed using the Turin criteria. In addition, the control group consisted of indeterminate thyroid nodules (FLUS [follicular lesion of undetermined significance] and FN [follicular neoplasm]) that were either benign or well-differentiated thyroid tumors on resection. The PDTC and control groups were both subjected to cytological assessment using specific cytological and architectural parameters, which included cellularity, growth pattern, mitoses, necrosis, chromatin change, discohesion, and anisonucleosis. RESULTS: A total of 36 thyroid FNAs were included in the study. This consisted of 12 histologically confirmed PDTC FNAs and 24 indeterminate thyroid FNAs (FLUS and FN, 12 each). The most frequent findings among PDTC groups were hypercellularity (75%), trabecular/insular growth pattern (58%), branching capillaries (67%), and cellular discohesion (92%). Necrosis (25%), ≥3 mitoses (50%), and anisonucleaosis (42%) were less frequently observed. A peculiar finding was the presence of adenoid cystic carcinoma-like globules in 50% of PDTC cases. Certain findings such as colloid, necrosis, mitoses, and cellular discohesion were helpful in differentiating the two groups. CONCLUSIONS: Thyroid fine-needle aspiration remains an essential diagnostic/triage tool for most thyroid nodules/tumors. PDTC can be diagnosed or at least suspected preoperatively based on the demonstration of certain architectural and cytological alterations. Although mitoses and necroses are not always readily identified, an elevated Ki-67 labeling expression could provide additional clues to the diagnosis in some cases.

A Rare Case of Metastatic Glioblastoma Diagnosed by Endobronchial Ultrasound-Transbronchial Needle Aspiration.

Glioblastoma is a common primary brain tumor that has a high mortality rate. Reports of intrathoracic metastases are uncommon, with the most commonly reported site for metastases are the lung and pleura. However, involvement of the mediastinum is not well documented, and few reports of confirmed mediastinal metastases diagnosed by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) exist. Herein, we report a rare case of metastatic glioblastoma to the thorax. A lady in her 40s has been previously diagnosed with intracranial glioblastoma with multiple incidences of disease recurrence despite treatment with chemoradiotherapy, adjuvant chemotherapy, and repeated surgical resections. She presented with dyspnea and pleural effusion, for which radiological imaging revealed lung, pleural, and mediastinal lesions. Further diagnostic workup with EBUS and pleural fluid sampling confirmed metastatic disease to both sites. The pleural fluid showed highly atypical cells positive for GFAP, and EBUS-TBNA immunostains were GFAP, S100, and synaptophysin positive, giving an overall picture consistent with metastatic glioblastoma. The patient was referred for palliative care, and unfortunately, she passed away after several months.

Adrenal gland fine needle aspiration: a multi-institutional analysis of 139 cases.

INTRODUCTION: Adrenal gland lesions span a range of entities from benign and malignant primary neoplasms to metastatic tumors. Fine-needle aspiration (FNA) provides a minimally invasive diagnostic tool to stage patients with known malignancy and procure material for molecular testing. This study characterizes the clinicopathologic associations of patients with adrenal gland FNA from 2 large hospitals. MATERIALS AND METHODS: FNAs were identified by query of electronic medical record from 2002-2019. Clinical and pathological information was collated and correlated with corresponding surgical diagnosis when available. RESULTS: Of 139 cases, the majority (n = 127, 91%) were adequate computed tomography-guided FNAs and included the following diagnoses: positive for malignancy (n = 77, 55%), negative for malignancy (n = 32, 23%), neoplastic cells present (n = 16, 12%), nondiagnostic (n = 12, 9%), atypical (n = 1, 1%), and suspicious for carcinoma (n = 1, 1%). The majority (94%, n = 72 of 77) of malignancies were metastatic tumors, most frequently carcinoma (n = 53 of 72, 74%), followed by melanoma (n = 11 of 72, 15%), lymphoma (n = 4 of 72, 6%), and sarcoma (n = 4 of 72, 6%). Metastatic carcinomas included lung (n = 21 of 72, 29%), genitourinary (n = 12 of 72, 17%), and hepatobiliary or gastrointestinal tract (n = 11 of 72, 15%) primaries. Primary adrenal neoplasms (n = 23) included adenomas (n = 11 of 23, 48%), pheochromocytomas (n = 4 of 23, 17%), and myelolipomas (n = 3 of 23, 13%). Thirty-two patients with metastases died of disease after median follow-up of 8 months. CONCLUSIONS: High specimen adequacy (n = 127, 91%) and low indeterminate rates (n = 2, 2%) are achieved with adrenal FNA. Most aspirated lesions represent metastases from primary lung carcinomas, but other primary sites including those below the diaphragm are part of the diagnostic differential. Adrenal metastasis was associated with a poor prognosis, with median survival of 8 months.

Acinar cell induced autolysis is a frequent occurrence in CytoLyt-fixed pancreatic fine needle aspiration specimens: An analysis of 157 cytology samples.

BACKGROUND: Although 10% formalin is a standard preservative in pancreatic FNAs, the effect of CytoLyt on pancreatic tissue preservation has not been systematically explored. METHODS: Smears and cell blocks from CytoLyt-fixed (CF-CBs) and formalin-fixed (FF-CBs) pancreatic FNAs were blindly reviewed without knowledge of the fixative used, and the presence of tissue/tumor autolysis was noted. Controls included FF-CBs from pancreatic FNAs, CF-CBs from nonpancreatic FNAs, and 4 pancreatic FNAs with matched CF-CBs and FF-CBs. RESULTS: We found that 62 of 85 (73%) pancreatic FNAs with CF-CBs showed significant autolysis, which was most pronounced in acinar cells and/or tumor cells with benign acinar cells in the background, compared with 2 of 46 (4%) FF-CBs (P < .0001) and 3 of 26 (12%) CF-CBs from nonpancreatic FNAs (73% vs 12%; P < .0001). Of the 4 pancreatic FNAs with matched CF-CBs and FF-CBs, all 4 CF-CBs showed marked autolysis versus none of the matched FF-CBs. Of the 23 (27%) pancreatic FNAs with CF-CBs that did not show autolysis, 10 had no acinar cells, and 7 had only minute tissue fragments on CB. CONCLUSION: While CytoLyt is a useful fixative for nonpancreatic FNAs it is a suboptimal fixative for pancreatic FNAs and is associated with tissue/tumor autolysis in the majority of cases, influencing morphologic evaluation, and potentially immunocytochemical staining. Autolysis appears to be due to acinar enzymes whose effect is likely interrupted/inhibited by formalin fixation. Cytopathologists and cytotechnologists should be mindful of this pitfall and should avoid using CytoLyt as a fixative for pancreatic FNAs.

Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germline CHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma.

We describe a woman with the known pathogenic germline variant CHEK2:c.1100delC and synchronous diagnoses of both pelvic genital type leiomyosarcoma (LMS) and metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a tumor-suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved in double-strand DNA break repair and cell cycle arrest. The CHEK2:c.1100delC variant is a moderate penetrance allele resulting in an approximately twofold increase in breast cancer risk. Whole-genome and whole-transcriptome sequencing were performed on the leiomyosarcoma and matched blood-derived DNA. Despite the presence of several genomic hits within the double-strand DNA damage pathway (CHEK2 germline variant and multiple RAD51B somatic structural variants), tumor profiling did not show an obvious DNA repair deficiency signature. However, even though the LMS displayed clear malignant features, its genomic profiling revealed several characteristics classically associated with leiomyomas including a translocation, t(12;14), with one breakpoint disrupting RAD51B and the other breakpoint upstream of HMGA2 with very high expression of HMGA2 and PLAG1 This is the first report of LMS genomic profiling in a patient with the germline CHEK2:c.1100delC variant and an additional diagnosis of metastatic invasive ductal breast carcinoma. We also describe a possible mechanistic relationship between leiomyoma and LMS based on genomic and transcriptome data. Our findings suggest that RAD51B translocation and HMGA2 overexpression may play an important role in LMS oncogenesis.

Bone marrow-derived microglia in pilocytic astrocytoma.

Tumour associated macrophages (TAMs) are increasingly recognized as supporters of tumour growth. The present study was undertaken to examine benign pilocytic astrocytomas (PAs) for the presence of M2 macrophages. We have asked the question whether TAMs in PAs share the predominant CD163 immunophenotype with tumour-associated microglia/macrophages of malignant gliomas. In addition, we were interested in the question whether there is evidence that the macrophages in PAs derive from resident microglia in surrounding normal brain or whether cells expressing a macrophage phenotype may invade PAs from the vasculature. The latter question is of great interest with regard to so-called "bone marrow-derived microglia" (BMDM) which may provide a physiological route of entry into the CNS that could be used for novel cell-based treatments of brain cancer. In fact, we have found strong morphological evidence for such macrophage recruitment into PAs. We propose therefore that PAs may be used as a model for the study of macrophage recruitment into gliomas. Importantly, our results also confirm that microglia/macrophage infiltration per se is not associated with malignant glioma behaviour.