{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T22:35:50Z","timestamp":1780612550970,"version":"3.54.1"},"reference-count":24,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T00:00:00Z","timestamp":1644105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["KL2 TR002015"],"award-info":[{"award-number":["KL2 TR002015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Enlarged lymph nodes are a common complaint in a Pediatrician\u2019s office. Diagnosis of reactive lymphadenopathy secondary to infectious, inflammatory, immune dysregulation calls for clinical investigation, including a thorough history, physical exam, imaging, and less often, a biopsy of the lymph node. Here we discuss a rare presentation of extensive generalized, chronic, waxing, and waning lymphadenopathy diagnosed as Progressive Transformation of Germinal Centers (PTGC) and the course of illness over eight years follow up period. Discussion: Progressive Transformation of Germinal Centers (PTGC) is considered a benign condition, but extensive recurrent generalized lymphadenopathy in a very young child has not been reported before. This case demonstrates the importance of long-term follow-up and tailoring the diagnostic work-up and management based on new signs and symptoms. Here we focus on the clinical considerations and management of complex presentation of a common clinical finding.<\/jats:p>","DOI":"10.3390\/children9020214","type":"journal-article","created":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T20:36:47Z","timestamp":1644179807000},"page":"214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Chronic Generalized Lymphadenopathy in a Child\u2014Progressive Transformation of Germinal Centers (PTGC)"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0356-3071","authenticated-orcid":false,"given":"Carson","family":"Wills","sequence":"first","affiliation":[{"name":"Department of Graduate Education, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Mercer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozef","family":"Malysz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidys","family":"Rivera Galvis","sequence":"additional","affiliation":[{"name":"Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4582-820X","authenticated-orcid":false,"given":"Chandrika","family":"Gowda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/hed.21448","article-title":"Sonographic assessment of cervical lymphadenopathy: Role of high-resolution and color Doppler imaging","volume":"33","author":"Gupta","year":"2011","journal-title":"Head Neck"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.suc.2010.10.012","article-title":"Positron emission tomography for benign and malignant disease","volume":"91","author":"Visioni","year":"2011","journal-title":"Surg. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/S0022-3468(99)90101-X","article-title":"Predictors of malignancy in childhood peripheral lymphadenopathy","volume":"34","author":"Soldes","year":"1999","journal-title":"J. Pediatr. Surg."},{"key":"ref_4","first-page":"764","article-title":"PET positive progressive transformation of germinal centers masquerading as relapsed Hodgkin lymphoma post-autograft","volume":"47","author":"Grigg","year":"2006","journal-title":"Leuk Lymphoma"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.2214\/AJR.12.8629","article-title":"Imaging of cervical lymphadenopathy in children and young adults","volume":"199","author":"Ludwig","year":"2012","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_6","first-page":"288","article-title":"Benign lymphadenopathies in children and adolescents","volume":"12","author":"Segal","year":"1995","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1542\/pir.29.2.53","article-title":"Evaluation and management of lymphadenopathy in children","volume":"29","author":"Friedmann","year":"2008","journal-title":"Pediatr. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.otc.2014.06.012","article-title":"Pediatric cervical lymphadenopathy","volume":"47","author":"Rosenberg","year":"2014","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pecora, F., Abate, L., Scavone, S., Petrucci, I., Costa, F., Caminiti, C., Argentiero, A., and Esposito, S. (2021). Management of Infectious Lymphadenitis in Children. Children, 8.","DOI":"10.3390\/children8100860"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1080\/08880010600856907","article-title":"Evaluation of peripheral lymphadenopathy in children","volume":"23","author":"Oguz","year":"2006","journal-title":"Pediatr. Hematol. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.otc.2014.09.010","article-title":"Pediatric inflammatory adenopathy","volume":"48","author":"Penn","year":"2015","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s003300101102","article-title":"Imaging of lymphadenopathy in the neck","volume":"12","author":"Castelijns","year":"2002","journal-title":"Eur. Radiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ijporl.2013.12.011","article-title":"When does an enlarged cervical lymph node in a child need excision? A systematic review","volume":"78","author":"Locke","year":"2014","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_14","first-page":"567","article-title":"Paediatric cervical lymphadenopathy: When to biopsy?","volume":"21","author":"Nolder","year":"2013","journal-title":"Curr. Opin. Otolaryngol. Head Neck Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1309\/UUEPLF2PHYXQDJNQ","article-title":"Follicular hyperplasia, follicular lysis, and progressive transformation of germinal centers. A sequential spectrum of morphologic evolution in lymphoid hyperplasia","volume":"120","author":"Chang","year":"2003","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0165-5876(02)00176-3","article-title":"Progressive transformation of germinal centers: Review of histopathologic and clinical features","volume":"65","author":"Hicks","year":"2002","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/pbc.24234","article-title":"Progressive transformation of germinal centers in children and adolescents: An intriguing cause of lymphadenopathy","volume":"60","author":"Shaikh","year":"2013","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1097\/00125480-200203000-00004","article-title":"Dismantling the germinal center: Comparing the processes of transformation, regression, and fragmentation of the lymphoid follicle","volume":"9","author":"Jones","year":"2002","journal-title":"Adv. Anat. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/pbc.24296","article-title":"A pediatric translational perspective on the entity \u201cprogressive transformation of germinal centers (PTGC)\u201d","volume":"60","author":"Miles","year":"2013","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1097\/00000478-198404000-00002","article-title":"Differential diagnostic features of nodular L & H Hodgkin\u2019s disease, including progressive transformation of germinal centers","volume":"8","author":"Burns","year":"1984","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_21","first-page":"135","article-title":"Progressive transformation of germinal centers: Comparison of 23 pediatric patients to the adult population","volume":"5","author":"Osborne","year":"1992","journal-title":"Mod. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/j.humpath.2015.07.006","article-title":"Immunoarchitectural patterns of progressive transformation of germinal centers with and without nodular lymphocyte-predominant Hodgkin lymphoma","volume":"46","author":"Hartmann","year":"2015","journal-title":"Hum. Pathol."},{"key":"ref_23","first-page":"547","article-title":"Classical Hodgkin lymphoma occurring in clusters of nodal marginal zone B-lymphocytes in association with progressive transformation of germinal center. A case report","volume":"199","author":"Kojima","year":"2003","journal-title":"Pathol. Res. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1097\/00000478-199203000-00005","article-title":"Florid progressive transformation of germinal centers. A syndrome affecting young men, without early progression to nodular lymphocyte predominance Hodgkin\u2019s disease","volume":"16","author":"Ferry","year":"1992","journal-title":"Am. J. Surg. Pathol."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/2\/214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:15:12Z","timestamp":1760134512000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/2\/214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,6]]},"references-count":24,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["children9020214"],"URL":"https:\/\/doi.org\/10.3390\/children9020214","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,6]]}}}