{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:16:48Z","timestamp":1790907408613,"version":"4.1.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy that frequently relapses after initial chemoradiotherapy. Bone marrow involvement in SCLC has been reported previously, but relapse confined predominantly to the marrow may be difficult to recognize when skeletal imaging remains negative. We report a diagnostically discordant presentation of relapsed SCLC characterized by rapidly progressive thrombocytopenia, marked biochemical progression without corresponding radiographic evidence of skeletal disease, and pathological confirmation of bone marrow metastasis supported by immunophenotypic and molecular findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case description<\/jats:title>\n                    <jats:p>A 76-year-old Chinese man was diagnosed with limited-stage right upper-lobe SCLC in August 2025. Initial positron emission tomography\/computed tomography showed a right upper-lobe lesion with mediastinal and right hilar lymph node involvement, without definite distant or skeletal metastasis; brain magnetic resonance imaging showed no intracranial metastasis. He received six cycles of etoposide plus carboplatin followed by thoracic radiotherapy to the right lung and mediastinum. Approximately 3 months after radiotherapy, he was admitted with fatigue and dyspnea. No antitumor therapy was administered between May 19 and June 6, 2026. During the final hospitalization, the platelet count decreased rapidly from 88\u00d710^9\/L to 18\u00d710^9\/L, accompanied by anemia, nucleated red blood cells, elevated lactate dehydrogenase and ferritin, and markedly increased tumor markers, including neuron-specific enolase, pro-gastrin-releasing peptide, carbohydrate antigen 125, and carbohydrate antigen 19-9. Chest and abdominal imaging and bone scintigraphy did not reveal definite bone metastasis. Bone marrow aspiration and biopsy performed on June 1 confirmed metastatic SCLC. Immunohistochemistry showed epithelial and neuroendocrine differentiation, mutant-type p53 expression, and loss of RB. Flow cytometry detected CD45-negative abnormal epithelial cells expressing CD326, CD56, and CD117. Targeted next-generation sequencing of the residual bone marrow specimen identified TP53 and RB1 alterations. Despite supportive treatment, the patient deteriorated rapidly and died on June 6, 2026.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This case highlights a clinically aggressive but radiographically occult pattern of SCLC relapse in which rapidly progressive cytopenias and biochemical progression preceded detectable skeletal abnormalities. Negative bone scintigraphy and the absence of destructive bone lesions should not delay bone marrow examination when the clinical and laboratory findings suggest marrow infiltration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1926902","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:49:22Z","timestamp":1787719762000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Radiographically occult bone marrow metastasis in relapsed small cell lung cancer presenting with rapidly progressive thrombocytopenia: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Jingli","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Shaoxing People\u2019s Hospital","place":["Shaoxing, Zhejiang, China"]},{"name":"School of Medicine, Shaoxing University","place":["Shaoxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Shaoxing People\u2019s Hospital","place":["Shaoxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijia","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Shaoxing People\u2019s Hospital","place":["Shaoxing, Zhejiang, China"]},{"name":"School of Medicine, Shaoxing University","place":["Shaoxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Shaoxing People\u2019s Hospital","place":["Shaoxing, Zhejiang, China"]},{"name":"School of Medicine, Shaoxing University","place":["Shaoxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Shaoxing People\u2019s Hospital","place":["Shaoxing, Zhejiang, China"]},{"name":"School of Medicine, Shaoxing University","place":["Shaoxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Shaoxing People\u2019s Hospital","place":["Shaoxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Center, Shaoxing People\u2019s Hospital","place":["Shaoxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Shaoxing People\u2019s Hospital","place":["Shaoxing, Zhejiang, China"]},{"name":"School of Medicine, Shaoxing University","place":["Shaoxing, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00235-0","article-title":"Small-cell lung cancer","volume":"7","author":"Rudin","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202413445","article-title":"Nuclear to cytoplasmic transport is a druggable dependency in HDAC7-driven small cell lung cancer","volume":"12","author":"Qin","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17020255","article-title":"Recent advances in the clinical translation of small-cell lung cancer therapeutics","volume":"17","author":"Das","year":"2025","journal-title":"Cancers"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-024-00914-x","article-title":"Emerging advances in defining the molecular and therapeutic landscape of small-cell lung cancer","volume":"21","author":"Sen","year":"2024","journal-title":"Nat Rev Clin Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202013122","article-title":"Mechanisms of small cell lung cancer metastasis","volume":"13","author":"Ko","year":"2021","journal-title":"EMBO Mol Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097-0142(19960501)77:9<1947::Aid-cncr27>3.0.Co;2-z","article-title":"The National Cancer Data Base report on lung cancer","volume":"77","author":"Fry","year":"1996","journal-title":"Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19890215)63:4<763::aid-cncr2820630426>3.0.co;2-f","article-title":"Bone marrow involvement in small cell lung cancer. 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