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Anjali Saqi

Publications and source records attributed to Anjali Saqi.

17 recordsLinked to original sources

Pulmonary fibrosis after COVID-19 is characterized by airway abnormalities and elevated club cell secretory protein-16.

BACKGROUNDThere are no known serum biomarkers that provide mechanistic insight or prognostic enrichment for post-COVID-19 pulmonary fibrosis.METHODSWe tested associations of serum biomarkers with radiographic fibrosis-like abnormalities (reticulation, traction bronchiectasis, or honeycombing) on thoracic computed tomography (CT) scans 4 months, 15 months, and 3 years after hospitalization in an American discovery cohort of severe-to-critical COVID-19 survivors, and externally validated findings in 2 Canadian cohorts of moderate-to-critical COVID-19 survivors. In the discovery cohort, we investigated the dose-response relationship of the biomarker with CT-derived airway-to-lung ratio. We performed single-cell RNA sequencing (scRNA-seq) of transbronchial lung biopsies from COVID-19 survivors obtained 3 years after COVID-19 hospitalization and conducted immunofluorescence analysis of COVID-19 lung explants.RESULTSAmong 150 discovery cohort participants, only higher levels of circulating club cell secretory protein-16 (CC16, encoded by the SCGB1A1 gene) at hospital discharge, 4 months, 15 months, and 3 years were associated with thoracic CT fibrosis-like abnormalities in cross-sectional and longitudinal analyses. Higher CC16 levels were associated with thoracic CT fibrosis-like abnormalities in 2 validation cohorts (n = 56 and n = 37). CC16 levels were linearly associated with increased airway-to-lung ratio. scRNA-seq revealed increased proportions of epithelial cells expressing SCGB1A1 and SCGB1A1/MUC5B in COVID-19 survivors with fibrosis. Immunofluorescence analysis of COVID-19 lung explants demonstrated increased numbers of SCGB1A1-expressing epithelial cells only in small (<100 &#x3bc;m) airways, with 3-fold more CC16/MUC5B-coexpressing cells in respiratory bronchioles..CONCLUSION. Higher CC16 levels are associated with CT fibrosis-like abnormalities for up to 3 years following moderate-to-critical COVID-19. Increased CC16 reflects dysregulated small airway epithelial progenitor cell remodeling and increased expansion of CC16+MUC5B+ epithelial cells in respiratory bronchioles after COVID-19.TRIAL REGISTRATIONNot applicable.FUNDINGDepartment of Defense, NIH, and Japan Society for the Promotion of Science for Young Scientists.

Humans↗

High-risk human papillomavirus DNA testing: a marker for atypical glandular cells.

Cervical/endocervical cytology screening has decreased morbidity and mortality, and implementing adjunctive human papilloma virus (HPV) DNA testing for atypical squamous cells of undetermined significance has improved the specificity for detecting premalignant squamous lesions. Currently, there are no guidelines to perform HPV DNA testing on cervical/endocervical ThinPreps with atypical glandular cells (AGC). To assess the potential role of HPV DNA testing on AGC cases, Hybrid Capture 2 (Digene Corp.) testing was performed on 144 cervical/endocervical AGC specimens. One hundred three of 144 cases had follow-up; 60/103 (58.3%) were high-risk HPV negative and 43/103 (42.3%) were high-risk HPV positive. Of 43 HPV-positive patients, 37 had adenocarcinoma in situ (AIS), atypical squamous cells of undetermined significance (ASCUS), or cervical squamous intraepithelial neoplasia, while only one patient without high-risk HPV had a squamous intraepithelial neoplasia. Furthermore, most high-risk HPV positive AGC cases harbored high-grade squamous intraepithelial lesion (HSIL) rather than AIS. Our data support HPV DNA testing of all AGC specimens to detect cervical, especially squamous, neoplasia.

Adenocarcinoma↗

Cervical chordoma masquerading as a thyroid neoplasm: a case report.

Chordomas are rare neoplasms of notochord derivation that arise along the craniospinal axis. Their incidence along the cervical spine and close proximity to the thyroid can pose diagnostic pitfalls. We report a case of a paraspinal mass juxtaposed adjacent to the thyroid with intranuclear inclusions of papillary carcinoma, abundant eosinophilic cytoplasm of an oncocytic lesion, and pleomorphism of anaplastic carcinoma that expressed thyroglobulin and emulated a malignant thyroid neoplasm. However, subsequent histological examination revealed a chordoma with perithyroidal soft-tissue invasion. This case highlights the significance of including chordoma in the differential diagnosis of a thyroid neoplasm and interpreting thyroglobulin reactivity warily, because its inadvertent tracking during fine-needle aspirates (FNAs) can produce false positive staining of nonthyroidal cells.

Aged↗

Utility of CD138 (syndecan-1) in distinguishing carcinomas from mesotheliomas.

CD138 (Syndecan-1) is a transmembrane heparan sulfate proteoglycan present on the surface of plasma cells and epithelial cells. CD138 is also expressed in some hematopoietic neoplasms and has recently been observed in carcinomas. We characterized CD138 expression in cell-block preparations of fluids/effusions, focusing on the distinction between carcinoma and mesothelioma. One hundred formalin-fixed, paraffin-embedded cell-block sections of fluids/effusions consisting of 58 metastatic carcinomas, 24 mesotheliomas, 11 reactive mesothelial cell proliferations, 3 lymphomas, 3 metastatic sarcomas, and 1 metastatic melanoma were stained with a monoclonal antibody against CD138. CD138 staining was observed in 32/58 (55%) metastatic carcinomas and 2/24 (8%) mesotheliomas; all reactive mesothelial cells, lymphomas, sarcomas, and melanoma were negative. CD138 is a highly specific marker in the differential diagnosis of carcinoma vs. mesothelioma. Distinct membranous staining without background staining of most inflammatory cells makes CD138 an ideal marker for cell-block preparations of fluids/effusions. It should be an integral component of the epithelial-mesothelial antibody panel.

Biomarkers, Tumor↗

Metastatic mammary carcinomas with endocrine features: potential diagnostic pitfalls.

Mammary carcinomas with endocrine differentiation (MCED) are an uncommon subtype of breast carcinomas that are morphologically indistinguishable from low-grade endocrine neoplasms arising in other organs. Aspirates of MCED yield relatively monotonous cells with eccentrically placed nuclei containing characteristic "salt and pepper" chromatin. In the breast, these features represent MCED. In extramammary sites, the differential is more extensive, and diagnosing MCED metastases to the lung, a common location for primary and metastatic endocrine tumors, can be a challenging task, with significant clinical implications. Although primary MCED have been described extensively in the cytology literature, secondary pulmonary MCED have not been reported to the best of our knowledge. We report three cases of MCED metastatic to the lung and present the cytological and immunohistochemical features.

Aged↗

Usefulness of CDX2 and TTF-1 in differentiating gastrointestinal from pulmonary carcinoids.

Carcinoids of different organs appear morphologically indistinguishable. We studied the usefulness of differential expression of CDX2 and thyroid transcription factor-1 (TTF-1) in 78 gastrointestinal and pulmonary carcinoids and their metastases (n = 10). CDX2 staining of gastric biopsy specimens with neuroendocrine hyperplasia (n = 11) and various gastritides (n = 10) was also performed. All ileal (6/6 [100%]), 6 (86%) of 7 appendiceal, 3 (75%) of 4 duodenal, 1 (50%) of 2 ampullary, 12 (33%) of 18 rectal, 6 (30%) of 20 pancreatic, and 1 (17%) of 6 gastric carcinoids expressed CDX2 with variable intensity; none of the pulmonary carcinoids stained. Of 15 pulmonary carcinoids, 8 (53%) stained with TTF-1, but none of the gastrointestinal carcinoids did. CDX2 and TTF-1 staining profiles of primary and metastatic carcinoids were similar. CDX2+ gastric endocrine cells had a distribution similar to that of gastrin and enterochromaffin cells but not enterochromaffin-like cells. Our results suggest that CDX2 and TTF-1 have high specificity for gastrointestinal and pulmonary carcinoids, respectively.

Adolescent↗

Adenoid cystic carcinoma of the breast diagnosed by fine-needle aspiration.

Fine-needle aspiration cytology remains a useful tool for preoperative diagnosis of breast lesions. We describe a case of adenoid cystic carcinoma (ACC) of the breast detected by ultrasound-guided fine-needle aspiration (FNA). Subsequent histopathology corroborated the diagnosis. ACC is a rare but distinctive neoplasm of the breast that can be accurately diagnosed by FNA. Its infrequent presentation, favorable prognosis, and relatively conservative management in the breast prompt us to reinforce its features.

Aged↗

Metastatic epithelioid angiosarcoma of the heart in peritoneal fluid.

Angiosarcoma is the most common malignant neoplasm of the heart. Recurrent pericardial effusions are a common manifestation of cardiac angiosarcomas. The diagnosis of metastatic disease in effusions is often established histologically; few cases have been described in exfoliative cytology. We report a case of metastatic cardiac epithelioid angiosarcoma in peritoneal fluid.

Adult↗

Columnar cell lesions: fine-needle aspiration biopsy features.

Columnar cell lesions (CCLs) have been described histologically. Frequently, they are noted in biopsies performed for calcifications and are associated with an increased risk of malignancy in the presence of atypia. We sought to characterize the cytological features of CCLs in fine-needle aspirations (FNAs). Twenty FNAs with subsequent histology diagnoses of CCL without carcinoma were reviewed retrospectively. Eighteen of 20 cases were classified as "atypical" on cytology; they had cohesive three-dimensional clusters of enlarged polygonal epithelial cells intermixed with myoepithelial cells in the centers and palisading columnar cells peripherally. Five of these had cytological or architectural atypia on subsequent biopsies, but no significant differences were noted among the 18 aspirates. Calcifications (2/18), snouts (9/18), and bipolar nuclei (11/18) were also identified. The remaining 2/20 FNAs were interpreted as negative because of scant cellularity. In conclusion, CCLs have characteristic cytological traits, and because they may be associated with carcinoma, their recognition is important.

Adult↗

Pulmonary tumor embolism: a review of the literature.

Dyspnea in a patient with cancer may have several causes, including infection, thromboembolism, metastases, and therapeutically induced cardiopulmonary disease. Pulmonary tumor embolism is an uncommon cause. Occlusion of the pulmonary microvasculature by tumor cells and associated thrombi can produce a subacute and progressive clinical picture that resembles thromboembolic disease. Unfortunately, microscopic tumor embolism is recognized rarely before death because of difficulty in establishing the diagnosis. We provide a review of the literature about the evaluation and diagnosis of this rare clinical entity.

Dyspnea↗

Recurrent eosinophilic mastitis.

Systemic diseases rarely present with manifestations in the breast. Disorders such as sarcoidosis and pyoderma gangrenosum have been described to produce signs and symptoms in the breast. Peripheral eosinophilia is a systemic disease associated with a finite group of conditions including asthma, allergic or atopic disease, collagen vascular disease, and parasitic infection. In addition it has been described in association with several malignancies. A 50-year-old woman with a history of asthma and significant eosinophilia presented with an enlarging breast mass. Complete excision of the mass revealed eosinophilic mastitis. Two years later the patient again presented with a large mass in the same breast. Repeat excision demonstrated the same pathology. The clinical significance of this lesion is important because it presents as an enlarging, painless, dominant mass. Excision is necessary for management and to conclusively rule out malignancy. Its recurrence despite excision to negative margins, however, may indicate that control of the eosinophilia--and possibly the underlying disorder--is important to prevent further recurrence.

Breast↗

Cytomorphologic features of fine-needle aspiration of metastatic and recurrent melanoma.

Melanoma is an aggressive malignancy with a growing prevalence. Although early detection and excision offer a potential cure, recurrences and metastases are not uncommon. Fine-needle aspiration (FNA) can play a vital role in their detection as a relatively noninvasive, rapid, and economical alternative for tracking disease evolution. Prior clinical history and classic cytological features of melanoma (loosely cohesive smear pattern and single cells with large nuclei, prominent nucleoli, and melanin pigment) aid in cytological diagnoses. However, not all melanomas contain melanin pigment or characteristic cytologic features. We examined a large series of melanoma cases to determine the incidence of melanin pigment, the most common cell morphology, and the presence or absence of apoptosis/necrosis associated with this highly aggressive neoplasm.

Adult↗

Overexpression of p16INK4A in liquid-based specimens (SurePath) as marker of cervical dysplasia and neoplasia.

Human papillomavirus (HPV) is recognized as a causal agent for cervical carcinomas. Assimilation of HPV oncogenes E6 and E7 into the host DNA promotes upregulation of cyclin dependent kinase inhibitor (CDKI) p16(INK4A), detectable by monoclonal antibody in the developing cervical cancer cells. The aim of this study was to 1) develop a protocol for p16(INK4A) immunocytochemical staining on SurePath preparations, and 2) determine its utility as an HPV marker on a spectrum of cervical reactive and neoplastic lesions. Seventy-two specimens consisting of 28 nonneoplastic/nondysplastic cases (NN), one reactive glandular cells (RGC), 27 low-grade squamous intraepithelial lesions (LSIL), 10 high-grade squamous intraepithelial lesions (HSIL), one squamous cell carcinoma (SCCA), four atypical glandular cells (AGUS), and two adenocarcinomas (ADCA) were reprepped by SurePath and antibody to p16(INK4A) applied at 1:100 dilution using the Dako Envision + System on the Dako Autostainer. Expression of p16(INK4A) within the nucleus principally and cytoplasm of at least 10-15 cells was considered positive. All initial Papanicolaou-stained discrepant cases (p16(INK4A) positivity of NN and RGC cases and lack of reactivity in LSIL, HSIL, and AGUS) were reviewed. Nine of ten (90%) HSIL, one (100%) SCCA, 21/27 (78%) LSIL, and some reactive and inflammatory specimens demonstrated the presence of p16(INK4A). Reevaluation of discrepant cases revealed that several were underinterpreted (four NN were LSIL, one RGC was AGUS) or overinterpreted (one LSIL was NN). Following reassessment, false-positive staining was present in only 1/25 (1.4%) NN. Six of 30 (20%) LSIL lacked p16(INK4A) positivity. One of 10 (10%) HSIL had no staining. Two of four AGUS did not react with p16(INK4A) antibody. Both SCCA (1) and ADCA (2) had positive expression. This study confirms the intimate relationship between p16(INK4A) and HPV cytopathic effect. The p16(INK4A) immunocytochemical stain can be applied to liquid-based cervical preparations. This technique offers a more objective approach to deciphering "gray areas" of gynecologic cytopathology.

Adult↗