ABSTRACT Background Liquid biopsy—here, the analysis of blood—has often focused on counting solitary circulating tumor cells (CTCs), a readout that omits the multicellular architecture governing metastasis. We summarize a hierarchical morphological taxonomy built on the circulating tumor microenvironment (cTME), then ask what an isolation method must deliver before that taxonomy can be applied at the microscope. Methods We appraised the literature on label‐free size‐selection (membrane filtration) of whole blood, comparing suction‐driven, microfluidic, and gravity‐driven platforms for recovery of intact multicellular units and for readability of the resulting preparations by routine cytologic stains and multiplex immunocytochemistry. The critique is paired with the authors' own single‐center experience, reported in labeled subsections. Results Circulating tumor‐associated cells (C‐TACs) form the functional cellular tier of the cTME: a “mobile niche” comprising a malignant core—solitary CTCs and circulating tumor emboli (CTE)—together with non‐malignant supporting partners. Antigen‐dependent capture disrupts these units and misses non‐epithelial partners, whereas size‐selection retains them by size and deformability, independently of surface phenotype. We propose the driving force, and hence the shear imposed on captured cells, as the primary axis for classifying these platforms—a testable hypothesis rather than an established result. Chemo‐response profiling of the intact collective by an independent group showed 97% concordance with radiological response in therapy‐naïve patients; in our own series, perioperative CTE detection stratified adjuvant chemotherapy benefit in non‐small cell lung cancer. Conclusion Size‐selection converts a liquid biopsy into a cytology slide, placing interpretation of the circulating tumor ecosystem within the existing competence of the diagnostic laboratory.
ABSTRACT Background Fine‐needle aspiration (FNA) cytology is frequently employed as the first‐line diagnostic approach for thyroid nodules and plays a crucial role in the identification of primary thyroid lymphoma (PTL). This study aimed to elucidate the clinical and cytopathological characteristics, as well as the diagnostic challenges associated with PTL as determined by FNA. Methods A retrospective analysis was conducted on data collected from January 2014 to December 2025 from patients diagnosed with thyroid lymphoma or suspected lymphoma via FNA cytology at Xijing Hospital. The analysis encompassed clinical presentations, radiological findings, cytomorphological and histomorphological features, ancillary studies, treatment modalities, and follow‐up outcomes. Results Of 23 patients, 16 women and 7 men, with a median age of 68 (range, 21–86) years were included. Among the 23 cases identified as lymphoma or suspicious for lymphoma through thyroid FNA cytology, 19 had corresponding histological diagnoses, including 4 thyroid core needle biopsies, 5 thyroidectomies, 5 cervical lymph node core needle biopsies, and 5 cervical lymph node excisions. Concordance between cytologic and histologic diagnoses was observed in 84.2% (16/19) of cases, while 3 cases exhibited discordance. Cytological and/or histological evaluations identified three extranodal marginal zone lymphomas of mucosa‐associated lymphoid tissue (MALT lymphoma), six diffuse large B‐cell lymphomas (DLBCL) subdivided into three germinal center B‐cell (GCB) and three non‐GCB subtypes, one high‐grade B‐cell lymphoma with MYC and BCL2 rearrangements, two follicular lymphomas, and three Hodgkin lymphomas. Furthermore, four cases of B‐cell lymphoma and two cases of suspected lymphohematopoietic neoplasms lacked definitive histological subtyping. All patients exhibited a symptomatic enlarging thyroid mass, with or without associated local and regional lymphadenopathy, and had no prior history of lymphohematopoietic disorders. Thyroid ultrasonography revealed hypoechoic nodules in 14 cases, mixed‐echoic nodules in 2 cases, and heterogeneous nodules in one case. Four patients had only a thyroidectomy, nine received only chemotherapy, two underwent surgery plus either radiotherapy or chemotherapy, two had chemotherapy combined with either autologous hematopoietic stem cell transplantation (Auto‐HSCT) or radiotherapy, and one was treated with rituximab. The follow‐up period ranged from 2 to 126 months, with 18 patients remaining alive, 2 deceased, and 3 lost to follow‐up. Conclusion PTL is a rare condition mainly affecting elderly women and usually of B‐cell origin. Accurate cytological diagnosis of aggressive B‐cell lymphoma is crucial to avoid unnecessary surgeries. While ancillary studies aid in distinguishing Hashimoto's thyroiditis from MALT lymphoma, diagnosis remains challenging due to the limited cellularity of FNA samples.
ABSTRACT Background Basaloid Squamous cell carcinoma (BSCC) is a rare subtype of squamous cell carcinoma whose cytomorphologic features on lung fine needle aspiration (FNAB) can mimic small cell lung carcinoma (SCLC), creating a diagnostic dilemma. As the distinction is critical for patient management and prognosis, this study aimed to determine if published cytological criteria can reliably differentiate these entities. Methods A 10‐year retrospective search of cytology archives yielded six cases of BSCC. These were compared to 15 confirmed SCLC cases. Key cytomorphologic parameters, including dispersal patterns, tissue fragment characteristics, architecture, and background elements, were systematically evaluated. Results BSCC cases consistently showed a predominantly cohesive tissue fragment pattern ( n = 6, 100%) with sharp, straight edges and peripheral palisading ( n = 6, 100%). Pseudorosettes ( n = 5, 83.3%) and keratinous debris ( n = 2, 33.3%) were also noted in BSCC. In contrast, SCLC cases typically showed discohesive cells and tissue fragments with irregular borders that lacked peripheral palisading. Conclusions Although no single feature is pathognomonic, a combination of architectural findings is useful in distinguishing BSCC from SCLC. The presence of cohesive tissue fragments with sharp edges and peripheral palisading strongly favors a diagnosis of BSCC.
Background Leptomeningeal carcinomatosis (LC) in patients with disseminated cancer has a grave prognosis and limited therapeutic options. Diagnosis is delayed due to low CSF volume and scant cellularity. This quality improvement project was undertaken to evaluate the diagnostic performance of CSF cytology in cases with radiologic evidence and the utility of immunohistochemical (IHC) testing in stratifying atypical cases.Methods A 5 years retrospective review of CSF cytology, oncology notes, and MRIs from patients with non-hematologic malignancy and clinical evidence of LC was performed. A total of 39 CSF samples from 28 patients with carcinomas were identified. Cytospins were prepared, and IHC was ordered at the discretion of the pathologist. Root cause analysis was applied to examine factors contributing to equivocal results.Results Of the 39 CSF samples, 49% were classified as positive for malignancy on CSF cytology, 12 as atypical/suspicious, and 8 as negative. Sixteen samples underwent IHC analysis, 11 of which confirmed the positive cytology results. IHC stains were performed only in 2 of the 12 atypical cases. Root cause analysis identified several contributors to diagnostic limitations: (1) small CSF volumes divided across multiple tests; (2) hypocellularity; (3) absence of standardized protocols for IHC use; and (4) pathologist reluctance to order IHC on cytology smears. In all cases where performed, IHC findings correlated with clinical and radiologic impressions.Conclusions This project highlights limitations of CSF cytology alone in diagnosing LC and demonstrates that adjunctive IHC testing improves diagnostic accuracy. Incorporation of IHC into routine evaluation of equivocal cases should be considered.
Chondromyxoid fibroma (CMF) is a rare, benign cartilaginous tumor composed of myxoid and fibrous components, accounting for approximately 1% of all bone tumors. It typically arises in the metaphysis of long bones, with epiphyseal involvement of the short tubular bones of the hand and foot being uncommon. We report the case of a 14-year-old girl who presented with pain and a gradually progressive swelling of the left great toe, occurring after a fracture sustained 2.5 years earlier. Radiological findings were suggestive of an aneurysmal bone cyst or giant cell tumor. Fine-needle aspiration cytology (FNAC) revealed hypercellular smears comprising pleomorphic oval to spindle-shaped cells along with dense, pink osteochondroid material; the cytological diagnosis was rendered equivocal, and malignancy could not be excluded. Subsequent histopathological examination showed a well-circumscribed tumor with a lobular architecture composed of alternating hypocellular and hypercellular areas of myxomatous stroma and immature cartilaginous cells, confirming a diagnosis of chondromyxoid fibroma. Although a low-grade tumor, CMF may show nuclear atypia histologically and can mimic chondrosarcoma; distinguishing between the two is of paramount importance to avoid over-diagnosis and unnecessarily aggressive treatment of this benign entity. Complete surgical resection with long-term follow-up remains the mainstay of management, given the relatively high rate of recurrence.
