Thymolipoma and lipofibroadenoma, two sides of the same coin?
Editorial Commentary

Thymolipoma and lipofibroadenoma, two sides of the same coin?

Michael den Bakker1 ORCID logo, Malgorzata Szolkowska2

1Department of Pathology, Maasstad Hospital, Rotterdam, The Netherlands; 2Department of Pathology, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland

Correspondence to: Michael den Bakker, MD, PhD. Department of Pathology, Maasstad Hospital, PO Box 9100, 3007 AC, Rotterdam, The Netherlands. Email: bakkerma@maasstadziekenhuis.nl.

Keywords: Mediastinum; thymus; lipoma; thymolipoma (TLP)

Received: 19 January 2026; Accepted: 28 April 2026; Published online: 12 June 2026.

doi: 10.21037/med-2026-1-0005

Thymolipoma (TLP) and lipofibroadenoma (LFA) are rare thymic tumours consisting of mature fat tissue and thymic gland tissue. While TLP in the 2021 World Health Organization (WHO) classification is classified as a mesenchymal tumour, LFA is included in the thymoma group, however, it is not referred to as thymoma, and it differs significantly from true thymomas morphologically and biologically. Both from a clinical and histologic standpoint TLP and LFA show considerable overlap and therefore the suggestion arises whether these two entities may not be simply on a spectrum of a single entity.

TLP is the most common lipomatous lesion of the prevascular mediastinum. Numerous case reports and several small series, in total encompassing approximately 300 cases have been published, generally focusing on the large size that these neoplasms may reach. TLP is most common in young adults but has been reported in children and older adults, without gender predilection (1). The tumours are often asymptomatic, when symptoms do occur these usually are a consequence of their large size and consist of shortness of breath and cough. However, a significant proportion, up to fifty percent of patients with TLP, suffer from myasthenia gravis (2). The histology of TLP consists of a combination of mature fat, thymic tissue with cortical and medullary zones, Hassall’s corpuscles and terminal deoxynucleotidyl transferase (TdT) positive immature thymocytes. The proportion of fat and thymic tissue varies from case to case, ranging from 50% to 95% (1). It has been argued that while TLP is characterized by the predominant adipocytic component, the thymic tissue component is also increased beyond normal levels (3,4). Rare TLP cases may have a minor component of myoid cells and/or sebaceous cells and the presence of collagenous tissue in TLP has led to the designation of thymofibrolipoma (TFL) (5,6). Very rarely TLP has been combined with thymoma, combinations with several subtypes have been reported (7). The pathogenesis of TLP is uncertain, postulated etiologies include fatty involution of hyperplastic thymic tissue, hamartoma and neoplasia (1,8,9). The latter either as lipoma combined with normal thymic tissue, combined thymoma and lipoma and involuted thymoma replaced by fatty tissue (4,8,10).

LFA is typically seen in young adults, although the age range is broad (17–64 years; Table 1). Three components are by definition present in LFA: (I) mature fat tissue; (II) hypocellular collagenous connective tissue; and (III) bland epithelial cells arranged in cords, ramifying through the fat and connective tissue. It is the branching aspect of the epithelial component which impart the similarity to fibroadenoma of the breast and hence its name (11). In the current [2021] WHO classification, six LFA cases are referenced, headed under thymic epithelial tumours, in contrast to TLP, which is considered a mesenchymal neoplasm (33). However, additional cases have been published, bringing the total up to 30 cases (Table 1). These cases include four cases that were originally reported as TFLs, which shows identical features to LFA and for all intents and purposes should be considered LFAs (5,6). Similar to TLP, LFA may be associated with thymoma, and patients may have autoimmune symptoms. A single case was reported to have myoid-, apocrine- and sebaceous cells (32). Initially, it was suggested that LFA did not contain immature (TdT positive) T-cells, however, this supposition was based on the six cases reported in the WHO fascicle, with the publication of additional cases it has become clear that thymocytes are usually present in LFA. To date LFA has behaved in a benign fashion without recurrence or metastasis.

Table 1

Cases reported as LFA and TFL

Case number (reference) Original diagnosis Sex Age (years) Symptoms, duration Size (cm); weight (g) Molecular investigations Associations Follow-up [month]
1 (11) LFA/B1 thymoma Male 62 Dyspnea, dizziness, PRCA ND ND PRCA No recurrence of tumor [80], PRCA relapse 2× after removal of tumor
2 (12) LFA Male 32 Incidental finding in work-up for pneumonia, 6 months 3 ND – ND
3 (13) LFA/B1 thymoma Male 56 Cough, expectoration, 2 weeks 4.5 ND – NED [24]
4 (14) LFA/B1 Female 23 Chest pain, dyspnea, 6 months 21; 2,180 ND – NED [12]
5 (15) LFA Male 21 Asymptomatic, incidental finding 10 ND – NED [46]
6 (16) LFA Male 20 Acute onset of fever and cough 23; 670 ND – NED [6]
7 (17) LFA/B1 thymoma Male 29 Cough, expectoration 6 months 6.5 ND – ND
8 (18,19) LFA/TH Female 55 Asymptomatic 4.5 ND – NED [12]
9 (20) LFA Male 29 Asymptomatic 6 ND – ND
10 (21) LFA Male 28 Asymptomatic, incidental finding 9 ND – NED [6]
11 (22) LFA Female 35 Fatigue, cough 26; 5,000 Molecular analysis no fusions (incl HMGA2) identified ANCA-associated vasculitis with renal involvement NED [12]; progressive renal deterioration
12 (23) LFA Female 64 Progressive dyspnea 16; 2,800 ND – NED [48]
13 (24) LFA Male 21 Fever, diarrhea 9.2 ND – NED [12]
14–18 (25) LFA Male 30 Incidental finding 6.8 ND – NED [120]
LFA Female 62 Incidental finding 7.2 ND – NED [60]
LFA Male 19 Incidental finding 9.5 ND – NED [54]
LFA Male 48 Incidental finding 4.0 ND – NED [30]
LFA Male 49 Incidental finding 3.5 ND – NED [12]
19 (26) LFA Male 17 Incidental finding in work-up for pneumonia 12.5 WES, RNA seq: no somatic mutations, copy number variations and gene rearrangements – NED [13]
20–22 (27) LFA Female 59 Chest tightness 3–4 ND – NED [19]
LFA Female 33 Incidental 12 ND – NED [7]
LFA Male 37 Dyspnea 12 ND – NED [30]
23 (28) LFA Female 30 Incidental 10.3 ND – NED [6]
24 (5) TFL Female 43 ND ND FISH: monoallelic 13q14 deletion – ND
25,26 (6) TFL Female 9 Incidental 9 ND – ND
TFL Male 32 Incidental 32 ND – ND
27 (29) TFL Female 9 Incidental 9 ND – ND
28 (30) LFA/TH Male 39 Myasthenia crises 2.3 ND MG ND
29 (31) LFA/TH Male 62 Persistent cough 16 ND – NED [24]
30 (32)† LFA (with myoid and sebaceous and apocrine change) Male 61 Incidental 11 ND – ND

†, poster not presented, not available. ANCA, anti-neutrophil cytoplasmic antibody; FISH, fluorescence in situ hybridization; LFA, lipofibroadenoma; MG, myasthenia gravis; ND, no data; NED, no evidence of disease; PRCA, pure red cell aplasia; RNA seq, RNA sequencing; TFL, thymofibrolipoma; TH, thymic hyperplasia; WES, whole exome sequencing.

Despite the fact that TLP and LFA are considered discrete entities and are listed in different chapters of the WHO classification, a case can be made that these entities are in fact tumours encompassing a single entity with variable histology. The single feature delineating TLP and LFA is the presence of the typical epithelial component in LFA, consisting of strands and cords of small bland plump spindle cells, while TLP typically has a component of organoid thymic tissue with immature thymocytes and plump epithelioid cells. However, in some TLP cases atrophic thymic epithelium forming elongated cords of cells in fatty tissue are reported (8). This typical epithelial component of LFA and in a minority of TLPs is morphologically similar to that seen in thymomas which have undergone regressive changes (formerly known as sclerosing thymoma), suggesting that regressive changes in a subset of TLPs may result in an appearance similar to LFA lending support for a common basis of LFA and TLP. However, the postulated occurrence of regressive changes in TLP is somewhat enigmatic as this does not appear to be correlated with either size or age, very large TLPs may not show any regressive changes while regression would paradoxically be a common occurrence in LFA, which in contrast to TLP do not tend to be as large. Additional histological features are shared between TLP and LFA. Both entities may occur in association with thymoma. Different types of thymoma have been reported in TLP (7), and four of the 27 reported LFA cases were associated with a B1 type thymoma (Table 1). Sebaceous- and in particular myoid cells have been reported in TLP (34), but this has only been reported in a single LFA case (32). The authors have on several occasions seen cases which bridge the spectrum TLP-LFA. A case with features of TLP, LFA and thymoma was reported with mainly organoid thymic tissue (75%), adipose tissue (10%) and an epithelial component of elongated cells embedded in fibrotic stroma (15%) (35). Another tumour (Figure 1, courtesy of Dr. T. Radonic, Department of Pathology, Amsterdam UMC, The Netherlands) which was removed from the mediastinum of a 21-year-old male, and weighing 4.7 kg, showed areas identical to LFA and TLP in a background of hyperplastic organoid thymic tissue. In addition to the histological similarity of TLP and LFA, the clinical features overlap. Both entities are distinctly more common in a younger age group. Although in the reported case, LFA shows a 2:1 male predominance, the number of cases is insufficient to draw firm conclusions. Both TLP and LFA are often asymptomatic and are discovered incidentally; when symptoms do occur these are either caused by the space occupying nature of the tumours, compressing lungs and resulting in cough, dyspnea and vague chest discomfort, or result from paraneoplastic activity. Both TLP and LFA are essentially benign tumours, surgical removal is curative, although paraneoplastic symptoms may persist even after removal of the tumour. The pathogenesis of both TLP and LFA remains enigmatic. Very few cases have been analyzed on a molecular level. A single TLP case was shown to harbor a HMGA2 translocation (10), which is common in lipomas, but this observation has not been repeated. Fluorescence in situ hybridization (FISH) analysis of one TFL/LFA case revealed monoallelic loss of 13q14 (5). Molecular analysis of two LFA cases did not revealed any aberrations (22,26).

Figure 1 Composite image of a case showing the TLP-LFA spectrum. Images of a 4.7 kg mass removed from the prevascular (anterior) mediastinum of a 21-year-old male. (A) Macroscopy image, thinly encapsulated multinodular mass. (B) TLP component with slightly disorganized thymic tissue; HE stained, original magnification 2.5×. (C) Lipofibroadenoma component consisting of strands of epithelial cells with hypocellular connective tissue and fat. HE stained, original magnification 5×. (D) TLP (left side) and LFA (right side) components. HE stained, original magnification 5×. Case courtesy of Dr. T. Radonic, Department of Pathology, Amsterdam UMC, The Netherlands. Reproduced with permission. The image is unpublished and not under copyright elsewhere. All patient information has been anonymized. HE, hematoxylin and eosin; LFA, lipofibroadenoma; TLP, thymolipoma.

Based on the clinical and histological similarity we propose to consider TLP and LFA (including four cases of TFL) a single entity with a histological spectrum, ranging from those cases with a predominant adipose background combined with organoid “bio-active” thymic tissue, complete with medullary and cortical areas and Hassall’s corpuscles, encompassing the TLP extreme of the spectrum, through to those at the LFA end of the spectrum consisting of tumours with atrophic and fibrotic thymic tissue embedded in mature fatty tissue.

Acknowledgments

The authors express their gratidue to Dr. T. Radonic, Department of Pathology, Amsterdam UMC, The Netherlands, for her permission to use Figure 1 in this manuscript.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Mediastinum. The article has undergone external peer review.

Peer Review File: Available at https://med.amegroups.com/article/view/10.21037/med-2026-1-0005/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-2026-1-0005/coif). M.S. serves as an unpaid editorial board member of Mediastinum from January 2026 to December 2027. M.d.B. serves as an unpaid editorial board member of Mediastinum from January 2026 to December 2027. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. The images were provided by Dr. T. Radonic (Department of Pathology, Amsterdam UMC, The Netherlands) with permission. The image was obtained in accordance with institutional ethical standards of the source institution. Written informed consent was obtained from the patient by the original provider, and all identifying information has been anonymized.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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doi: 10.21037/med-2026-1-0005
Cite this article as: den Bakker M, Szolkowska M. Thymolipoma and lipofibroadenoma, two sides of the same coin? Mediastinum 2026;10:32.

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