Pulmonary Metastasizing Ameloblastomas Can Masquerade as Certain Bronchiolar Adenoma‐Like Tumor With Squamous Epithelial Metaplasia

ABSTRACT

Bronchiolar adenoma (BA) is a generally benign peripheral lung neoplasm with a bilayered structure of basal and luminal cells. Recently, an increasing number of bronchiolar adenoma—like tumor with squamous epithelial metaplasia (BATSM) have been reported, raising the question of whether they represent variant subtypes of BA or potentially novel tumor entities. Pulmonary metastasis of ameloblastoma (MA) shares morphological similarities with BATSM, exhibiting TTF‐1/Napsin A‐positive luminal cells and P40/P63‐positive basal cells; this overlap can lead to misdiagnosis of MA as BATSM. We collected 5 MA and 10 BATSM cases, analyzing their morphology, immunohistochemistry, elastic fiber staining and molecular pathology. MA presents as well‐circumscribed bronchiole‐unrelated nodules with alveolar destruction, intraluminal serous secretions, and Calretinin‐positive stellate reticulum‐like cells. BATSM is bronchiole‐associated, preserves alveolar architecture, and is Calretinin‐negative with weak basal TTF‐1 positivity. 80% of MA cases harbored BRAF V600E mutations; 30% of BATSM cases exhibited EGFR exon 20 insertions. This study highlights the need for integrating clinical history, morphology, immunohistochemistry and molecular testing to avoid misdiagnosing MA as BATSM.

We found that those with histomorphology resembling so‐called “bronchiolar adenoma with squamous metaplasia” are in fact more akin to pulmonary metastases of ameloblastoma in terms of morphology, molecular profile harboring BRAF V600E mutations, and clinical characteristics be linked to a prior history of ameloblastoma.

1. Introduction

Bronchiolar adenoma (BA) is a rare benign tumor arising from the bronchial mucosal epithelium, first proposed in recent years [1]. It encompasses distal and proximal subtypes [2]. In 2021, this tumor was incorporated into the 5th edition of the WHO Classification of Thoracic Tumors, with an ICD‐O code of 8140/0 [3]. While the diagnosis of classic BA is typically achievable with immunohistochemical confirmation, some cases present variations—including partial basal cell loss or metaplasia, significant increases in luminal cell atypia, and malignant transformation [4, 5, 6, 7]. Consequently, controversy persists regarding whether certain cases represent BA subtypes or entirely independent entities.

Numerous studies have reported tumors exhibiting BA‐like morphology accompanied by basal cell squamous metaplasia [5, 7]. Teng et al. [7] described cases with frequent BRAF V600E mutations, proposing them as a distinct BA subtype‐bronchiolar adenoma with squamous metaplasia (BASM). Zheng et al. [5] reported 10 cases of frequent EGFR exon 20 insertion in the so‐called peripheral‐type squamous cell neoplasm of uncertain malignant potential (PSCN‐UMP). In addition, we have found that some cases exhibit typical BA morphology accompanied by focal squamous metaplasia. In this study, we used the term ‌bronchiolar adenoma ‐ like tumors with squamous epithelial metaplasia (BATSM)‌. This BATSM concept includes BASM and PSCN ‐ UMP mentioned in the cited literature, as well as some cases with typical BA morphology accompanied by focal squamous metaplasia.

We found that pulmonary metastasizing ameloblastoma (MA) has morphological overlap with the BATSM, which can easily lead to misdiagnosis. To address this diagnostic challenge, the present study enrolled 5 cases of MA and 10 cases of BATSM. We comprehensively analyzed and compared these cases based on morphological features, immunophenotypes, molecular profiles, and clinical characteristics.

2. Materials and Methods

2.1. Case Data

We collected 5 cases of MA and 10 cases of BATSM diagnosed at Shanghai Pulmonary Hospital Pathology Department (January 1, 2012 to December, 31, 2025). Of the 10 BATSM cases, 6 were identified as PSCN‐UMP, including 4 previously reported by Zheng et al. [5], and the remaining 4 were classic BA with focal squamous metaplasia. Clinicopathological and imaging data were collected and summarized in Table 1.

Table 1.

Clinical data, immunohistochemistry, and molecular results of 15 cases.

Group	Case no.	Sex	Age	Size (mm)	Medical history of ameloblastoma	Histology				Immunohistochemistry					EEFc	Molecular
						Near small airways/arteries	Clear boundaries	Squamous metaplasia patterns	With adenoid structure and lumen gel‐like secretions	Luminal cells TTF‐1/napsin A	Basal cells calretinin	Basal cells TTF‐1 positive	Basal cells P40/P63	Ki67 (%)
MAa	1	M	47	4–8 Multiple	Yes (18 years ago)	(−)	(+)	Diffuse	(+)	(+)	Stellate reticulum‐like (+)	(−)	(+)	5	No Intact	Wild Type
	2	F	44	9–34 Multiple	Yes (40 years ago)	(−)	(+)	Diffuse	(+)	(+)	Stellate reticulum‐like (+)	(−)	(+)	2	No Intact	BRAF Exon15 V600E
	3	F	35	35	Yes (5 years ago)	(−)	(+)	Diffuse	(+)	(+)	(−)	(−)	(+)	10	No Intact	BRAF Exon15 V600E
	4	M	52	9	Yes (4 years ago)	(−)	(+)	Diffuse	(+)	(+)	(−)	(−)	(+)	1	No Intact	BRAF Exon15 V600E
	5	F	58	3–9 Multiple	Yes (8 years ago)	(−)	(+)	Diffuse	(+)	(+)	Stellate reticulum‐like (+)	(−)	(+)	5	No Intact	BRAF Exon15 V600E
BATSMb	6	F	68	10	No	(+)	(−)	Diffuse	(−)	(+)	(−)	Weekly (+)	(+)	1	Intact	EGFR 20ins
	7	F	70	8	No	(+)	(−)	Diffuse	(−)	(+)	(−)	Weekly (+)	(+)	NA	Intact	EGFR 20ins
	8	M	68	15	No	(+)	(−)	Diffuse	(−)	(+)	(−)	Weekly (+)	(+)	NA	Intact	Wild Type
	9	F	65	21	No	(+)	(−)	Diffuse	(−)	(+)	(−)	Weekly (+)	(+)	1	Intact	Wild Type
	10	F	65	18	No	(+)	(−)	Diffuse	(−)	(+)	(−)	(−)	(+)	1	Intact	Wild Type
	11	F	67	10	No	(+)	(−)	Diffuse	(−)	(+)	(−)	Weekly (+)	(+)	2	Intact	EGFR 20ins
	12	M	78	21	No	(+)	(−)	Focal	(−)	(+)	(−)	(−)	(+)	5	Intact	Wild Type
	13	M	67	13	No	(+)	(−)	Focal	(−)	(+)	(−)	Weekly (+)	(+)	NA	Intact	Wild Type
	14	F	61	6	No	(+)	(−)	Focal	(−)	(+)	(−)	Weekly (+)	(+)	2	Intact	NA
	15	M	47	5	No	(+)	(−)	Focal	(−)	(+)	(−)	(−)	(+)	5	Intact	NA

^a MA: Metastasizing ameloblastoma.

^b BATSM: So‐called BA with squamous epithelial metaplasia.

^c EEF: Expression of elastin fiber.

2.2. Methods

Specimens were fixed in 4% neutral buffered formalin, paraffin‐embedded, sectioned (4 μm), and hematoxylin‐eosin staining (H&E staining). Immunohistochemistry (IHC) used the EnVision method with antibodies: CD10, Ki‐67, P63, thyroid transcription factor‐1 (TTF‐1, 8G7G3/1), CK5/6, SMA, S‐100 and Calretinin(DAK‐calret1) (All the above antibodies and kits were purchased from Dako, Denmark); P40 and Calponin (Beijing Zhongshan Golden Bridge Biotechnology Co. Ltd.), CK(AE1/AE3) (Shanghai Changdao Biotechnology Co. Ltd.). Cases with a BRAF V600E mutation detected by molecular testing were additionally subjected to BRAF V600E IHC staining. Staining was performed on a Dako Autostainer Link 48 platform with controls. The elastic fiber staining is carried out using the victoria blue (VB) staining. For VB staining, the tissue slices were submerged in a solution of VB for 10−24 h, differentiated with 95% ethanol for 10 s until no further color removal, rinsed with running tap water, counter stained with Van Gieson stain, dehydrated with 95% anhydrous ethanol, cleared with xylene, and sealed with neutral resin adhesive.

2.3. PCR‐Based Gene Detection for Lung Tumors

The specific operation steps for detecting mutations in 10 common genes of lung cancer (including EGFR, ALK, ROS1, KRAS, BRAF, Her2, C‐MET, RET, PIK3CA, and NRAS) follow the “Ed Mutation Gene Detection Kit (Fluorescence PCR Method) Manual.”

3. Results

3.1. Clinical Data

Five cases of MA, three were female and two were male. The age of the patients ranged from 35 to 58 years, with a median age of 47 years. Among them, all cases had a history of ameloblastoma, and the distance from the discovery of pulmonary nodules ranged from 4 to 40 years. 10 cases of BATSM, 6 were female and 4 were male. The age of the patients ranged from 47 to 78 years, with a median age of 66 years (Table 1).

3.2. Imaging Examination

MA: Imaging suggested the maximum diameter range of the lesion was 3 to 35 mm, with an average of 14 mm. Among them, three cases were multiple (Figure 1A,E) and two cases were single.

Figure 1.

The chest CT manifestations, histopathological and immunohistochemical features of pulmonary MA. Case 2 (A–D): In group MA case 2, scattered multiple nodular shadows were seen in both lungs (indicated by the yellow arrow) (A). The tumors appear as multiple well‐circumscribed nodules that are clearly demarcated from the surrounding lung parenchyma (B), lack obvious alveolar framework, and contain numerous glandular/papillary structures lined with columnar or cuboidal cells. Some serous secretions are present in lumens (C), with spindle/oval tumor cells between glands (D); no cellular atypia, mitoses, or necrosis. Case 5 (E–H): In group MA case 5, scattered multiple nodular shadows were seen in both lungs (indicated by the yellow arrow) (E). Tumors have clear boundaries with surrounding lung tissue with necrosis within the cavity (F). The cellular nests among the glandular/papillary structures contained mostly spindle or ovoid tumor cells with a poorly defined cytoplasm (G). Focal squamous metaplasia could be observed (H). Immunohistochemical of MA case 2 (I–L): Basal cells focally positive for Calretinin, luminal columnar cells negative for Calretinin (I). Basal cells diffusely positive for BRAF, type II alveolar epithelial cells in the lumen negative for BRAF (J). TTF‐1 positivity in type II alveolar epithelial cells lining the lumen (K). Basal cells diffusely positive for P40 (L). ○ indicates the epithelial squamous metaplasia area; the red → indicates the luminal cells; * indicates the basal cells.

BATSM: Imaging suggested the maximum diameter range of the lesion was 5 to 21 mm, with an average of 13 mm. All of the 10 cases were single (Figure 2A,E).

Figure 2.

The chest CT manifestations and histopathological features of pulmonary lesions with BATSM. Case 11 (A–D): In group BATSM case 11, a single nodular shadow was observed in the right lower lobe (A) (indicated by the yellow arrow). Tumors show continuity with normal alveoli, are closely connected to bronchiolar artery bundles or penetrated by fibrous bundles under low magnification (B). All have biphasic components: luminal cells are flat to cuboidal (similar to type II pneumocytes) with sparse eosinophilic cytoplasm and small nuclei; basal cells show mild squamous metaplasia (C). The hyperplastic squamous epithelium appears as solid, sheet‐like structures (D). Case 13 (E–H): In group BATSM case 13, a single nodular shadow was observed in the left lower lobe, and there is a cavity formed in the middle of the nodule (E) (indicated by the yellow arrow). Tumors show continuity with normal alveoli and are closely related to bronchovesicular bundles (F). Histologically, they have a double‐layered structure of basal and luminal cells (G), with sheet‐like spindle‐polygonal cells with significant squamous metaplasia (H). △ indicates the connected bronchus; ○ indicates the epithelial squamous metaplasia area.

3.3. Pathological Characteristics

3.3.1. Gross Features

Upon gross pathological examination, all tumors were relatively well‐circumscribed. The tumors were greyish‐tan to yellow, as observed on cut tissue sections.

3.3.2. Histological Findings

All cases showed a double‐layered morphology under the microscope, and the basal layer was accompanied by varying degrees of squamous epithelial metaplasia. According to the comparison of histomorphology, cases of MA showed no significant association with the bronchioles and accompanying pulmonary arteries, had a clear boundary with the surrounding lung parenchyma, lacked a distinct alveolar structure framework, and showed formed numerous adenoid structures. The tumor cells were all well circumscribed and interspersed with any glandular/papillary structures and cellular cords or nests. The glandular/papillary elements consisted of columnar or cuboidal epithelial cells in the lumens. The cellular nests interspersed within these structures contained mostly spindle or ovoid tumor cells with a poorly defined cytoplasm. Focal squamous metaplasia was also noted. There were also gelatinous intraluminal secretions in the lumen of the tumor (Figure 1) (Figure S1: comparative H&E staining features of case 3 metastasizing ameloblastoma vs. primary ameloblastoma). BATSM: They were close to the bronchioles or accompanying pulmonary arteries, and the tumors had a clear alveolar structure framework and a certain continuity with the surrounding normal alveoli. The basal layer of the tumors was composed of relatively bland non‐keratinized stratified squamous cells, the squamous epithelium showed varying degrees of metaplasia (Figure 2). Among them, six cases have relatively diffuse squamous epithelial metaplasia ‌(Figure 2B–D) (Figure S2); four cases have relatively localized squamous epithelial metaplasia, accompanied by classic BA areas ‌(Figure 2F–H) (Figure S3). The proliferated squamous epithelium was presented as; scale‐like, inverted papillary or solid nest‐like (Figure 2D,H).

3.3.3. Immunohistochemistry and Elastin Fiber Staining

We conducted immunohistochemistry and elastin fiber staining analyses. The cohort contained 15 tumors, including 10 BATSM and 5 MA specimens, all of which demonstrated a consistent bilayered immunophenotype. Luminal cells were diffusely positive for TTF‐1 and Napsin A. Basal cells stained positively for P40 and P63, while they were negative for Napsin A, Calponin, S‐100, and SMA (Figure 3). Basal cells were uniformly TTF‐1‐negative in all 5 MA cases. In contrast, basal cells from 7 of the 10 BATSM cases displayed weak TTF‐1 positivity diffusely. Additionally, 3 cases of MA were positive for calretinin (3/5), and all 10 cases of BATSM showed negative expression of calretinin. The calretinin positive tumor areas all corresponded to the squamoid/stellate reticulum‐like component of MAs, while all columnar cells were negative. Among the 2 calretinin‐negative MA cases, tumor cells were predominantly columnar cells, with no obvious squamoid/stellate reticulum‐like component. Moreover, calretinin expression was negative in all 10 BATSM cases. The Ki‐67 proliferation index was low, ranging from 1% to 10% (Table 1). The BRAF V600E immunohistochemical detection in four cases from group MA showed all cases with basal cell positivity and luminal cell negativity ‌(Figure 1J). In group of pulmonary MAs, the elastic fibers in the tumors were significantly reduced, with only a few remnants remaining, and the remaining elastic fibers were discontinuous and not connected to each other. In contrast, the elastic fibers in the BATSM were continuous and intact, and had a clear continuity with the surrounding normal alveolar epithelium (Figure 3).

Figure 3.

Immunohistochemical and elastic fibers staining of MA and BATSM. Group MA (A–C): Basal cells diffusely positive for P40 (A); luminal cells diffusely positive for TTF‐1 (B); elastic fibers significantly reduced, remaining ones discontinuous and disconnected (C). Group BATSM of diffuse squamous metaplasia (D–F): Basal cells diffusely positive for P40 (D); luminal cells diffusely positive for TTF‐1, basal cells diffusely weak positive for TTF‐1 (E); elastic fibers continuous and intact (F). Group BATSM of local squamous metaplasia (G–I): basal cells focally positive for P40 (G); luminal cells diffusely positive for TTF‐1 (H); elastic fibers continuous and intact (I).

3.3.4. Molecular Testing

Among the five cases MA, four cases harbored the BRAF V600E mutation, and 1 case had a wild‐type gene. While, among the 10 cases BATSM, 3 cases had an EGFR 20 exon insertion with diffuse squamous epithelial metaplasia, 5 cases had wild‐type genes, and 2 cases were not performed (Table 1). The immunohistochemical and molecular findings are summarized at the group level (Table 2).

Table 2.

Immunohistochemical and molecular findings in MA and BATSM.

Features	MA (n = 5)	BATSM (n = 10)
Immunohistochemistry
Basal cells Calretinin positive	60% (3/5)	0% (0/10)
Basal cells TTF‐1 positive	0% (0/5)	70% (7/10)a
Basal cells P40/P63 positive	100% (5/5)	100% (10/10)
Luminal cells TTF‐1/Napsin A positive	100% (5/5)	100% (10/10)
Expression of elastin fiber integrity	0% (0/5)	100% (10/10)
Molecular Findings
BRAF V600E mutation	80% (4/5)	0% (0/10)
EGFR exon 20 insertion	0% (0/5)	30% (3/10)

Abbreviations: BATSM, bronchiolar adenoma‐like tumor with squamous epithelial metaplasia; MA, metastasizing ameloblastoma.

^a Weak positivity in basal cells.

4. Discussion

BA‐like morphology accompanied by basal cell squamous metaplasia have sparked ongoing debate regarding their classification as distinct tumor entities. In this study, we adopted the term bronchiolar adenoma‐like tumor with squamous epithelial metaplasia (BATSM) to unify previously reported BASM [7], PSCN‐UMP [5], and BA cases with focal squamous metaplasia. Notably, pulmonary metastasizing ameloblastoma (MA) closely mimics BATSM morphologically, leading to frequent misdiagnosis in routine practice. Our study therefore aimed to define the distinguishing features between these two lesions. Although all 15 cases shared a similar bilayered morphology, careful evaluation identified distinct differentiating features. Pulmonary MA showed no association with bronchioles or pulmonary arteries, featured well‐defined borders and absent alveolar architecture, and had markedly decreased, discontinuous elastic fibers. These changes indicate destruction of native alveolar structures and support a metastatic origin. Prior studies reported analogous lesions misdiagnosed as primary lung tumors, largely due to their bilayered structure and TTF‐1/Napsin A positivity in luminal cells [8, 9]. Notably, extrapulmonary metastases often infiltrate beneath the alveolar epithelium while sparing resident alveolar cells; Our immunohistochemical analyses confirmed BRAF immunoreactivity is observed in basal cells but the TTF‐1‐positive epithelial cells are negative for BRAF (Figure S1), verifying the latter as residual alveolar epithelial cells rather than bona fide tumor cells. In contrast, BATSM lesions were closely adjacent to bronchioles and pulmonary arteries, retained intact alveolar frameworks and continuity with adjacent normal alveoli, along with continuous elastic fibers, confirming their primary bronchiolar origin [10]. Another potential differential diagnostic point is that obvious columnar cells are present in all metastatic MAs, and these columnar cells can be detected on both the side adjacent to the alveolar lumen and the side adjacent to the stroma. On the side adjacent to the alveolar lumen, columnar cells grow mixed with invaginated alveolar epithelium, so they are easily mistaken for non‐neoplastic alveolar epithelium and overlooked. Double staining for P40/TTF‐1 can confirm the coexistence of the two cell types (Figure S4). On the other hand, the columnar cells on the stroma‐adjacent side are confirmed as neoplastic cells of MA by their definite P40 positivity and TTF‐1 negativity. At least some of these columnar cells correspond to the peripheral palisading columnar cells characteristic of ameloblastoma, particularly when they show a P40‐positive/TTF‐1‐negative phenotype. These distinct P40‐positive and TTF‐1‐negative columnar cells were not detected in any of the other BATSM cases in this study. Additionally, in our study, the presence of ‌multiple nodules, calretinin expression and intraluminal secretions‌ is more supportive of a diagnosis of MA. For BATSM, the combined pattern of weak TTF‐1 expression and diffuse P40 expression in multilayered tumor nests serves as a core immunophenotypic marker to distinguish it from MA.

Beyond clinical and morphological characteristics, molecular changes vary in different tumors, a feature that aids in determining tumor origin. There are diverse types of gene mutations in BA, with BRAF mutations being the most prevalent. The other common types include EGFR [11], KRAS [10], and ALK [2]. In the group of pulmonary MAs, up to 80% (4/5) of the cases had BRAF V600E mutation. The BRAF V600E mutation is not organ ‐ specific and can be detected in both intra ‐ and extra ‐ pulmonary tumors, including BA. As a whole, the MA group had a much higher BRAF mutation rate than typical BA. According to literature review, the BRAF mutation rate in cases of BA is approximately 30%–38% [1, 10, 12]. In the cases reported by Teng et al. [7] with BA‐like features and basal squamous metaplasia, 100% of the cases had BRAF mutations, which raised concerns about whether these cases might be pulmonary MA rather than a specific variant subtype of BA. In our study, 30% (3/10) of the cases were detected with EGFR exon 20 insertion mutations in BATSM cases. No case with BRAF V600E mutation was found. Both BA and ameloblastoma are histologically benign. Ameloblastoma rarely metastasizes (2%–5%) [13], and there are no histologic features that would predict metastases. However, when it does metastasize, lung is one of the most common metastatic sites. It is important for pathologists to be aware of this morphologic pitfall, particularly given the tumor's rarity, the metastasis tends to occur decades after the primary tumor, and it is morphologically similar to BATSM. Currently, there is no established guideline for the management of MA due to its extreme rarity, but there are case reports of treatment with chemotherapy and radiation. In contrast, adjuvant treatment is typically not required for BA [14, 15], highlighting the clinical importance of accurate distinction.

The reasons for the easy misdiagnosis of pulmonary MA include: (1) The pulmonary and maxillofacial surgery are relatively independent, and specialists in the pulmonary specialty have fewer opportunities to encounter ameloblastoma cases, and they are less familiar with the histological morphology of ameloblastoma [16, 17]; (2) Since the biological behavior of most ameloblastomas is relatively indolent, even aggressive cases tend to recur locally rather than metastasize distantly, leading to the possibility of metastasis being easily overlooked by clinical physicians and pathologists during the collection of clinical history [18]; (3) As reported in the literature, the recurrence time of metastasis is long, with an average of 14–18 years [19]. The duration of our cases ranges from 4 years to 40 years. In some cases, the disease onset occurred in the childhood. Since the patients lack recall of the event, confirmation relies on parental reports of the medical history; (4) Before the concept of BA emerged, some cases with similar morphology, apart from the special primary tumors in the lungs, might have prompted pathologists to more actively explore the disease history in order to avoid misdiagnosis. After the concept of BA emerged, since these tumors have overlapping pathological morphology with BA, they are more likely to be simply classified as a specific variant subtype of BA. It should be noted that while imaging (often multiple lesions), medical history (with a history of ameloblastoma), and molecular markers (frequent BRAF mutations) can help confirm that some tumors are pulmonary MA. Some pulmonary MA may also appear as solitary lesions. Additionally, BA can also exhibit BRAF mutations, and more importantly the history of ameloblastoma may sometimes be difficult to uncover, all of which increase the risk of misdiagnosis. Comprehensive evaluation of clinical history, imaging, histology, immunohistochemistry and molecular testing is therefore mandatory. In conclusion, since the description of BA concept, some cases with BA‐like morphology accompanied by varying degrees of squamous epithelial metaplasia were reported. It is worth noting that the pulmonary MA shows overlapping pathological manifestations with this type of tumor. Given their different biological behaviors and clinical management strategies, we emphasize a multimodal diagnostic workflow to avoid misdiagnosis. When encountering BA‐like morphology accompanied by basal cell squamous metaplasia, pathologists and clinicians should maintain a high level of vigilance to rule out metastatic ameloblastoma.

Author Contributions

Shengnan Zhao: conceptualization, methodology, writing – original draft. Jianjun Li: conceptualization, methodology, writing – original draft. Likun Hou: data curation, formal analysis, investigation. Yan Huang: data curation, formal analysis, investigation. Zhengwei Dong: data curation, formal analysis, investigation. Wei Wu: resources, visualization. Wei Zhang: resources, visualization. chunyan wu: writing – review and editing, supervision, project administration. Huikang Xie: writing – review and editing, supervision, project administration. All authors have read and agreed to the published version of the manuscript.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Figure S1: H&E staining of the metastatic lesions of ameloblastoma (A‐C): The tumors had a clear boundary with the surrounding lung tissue (A), lacked a distinct alveolar structure framework, and showed numerous adenoid structures (B). The intercellular bases of the glands showed stratified spindle‐shaped or oval‐shaped squamous cells (C). H&E staining of the primary lesions of ameloblastoma (D–F): The H&E staining of the primary lesion and the metastatic lesion of the ameloblastoma is similar.

Figure S2: H&E staining and immunohistochemical of group BATSM of diffuse squamous metaplasia: Tumors show continuity with normal alveoli under low magnification (A). They were close to the bronchioles or accompanying pulmonary arteries (B). The hyperplastic squamous epithelium appears as solid, sheet‐like structures (C). Immunohistochemical basal results indicate basal cells diffusely positive for P40 (D) and CK5/6 (E); luminal cells diffusely positive for TTF‐1 (F). We used P40 and elastic fiber double staining (D), as well as TTF‐1 and elastic fiber double staining (F). The elastic fibers in the BATSM were continuous and intact, and had a clear continuity with the surrounding normal alveolar epithelium (D) and (F).

Figure S3: H&E staining and immunohistochemical of group BATSM of local squamous metaplasia. Tumors show continuity with normal alveoli under low magnification (A). They were close to the bronchioles or accompanying pulmonary arteries (B). The squamous epithelium appears as focal nodular hyperplasia (C). The elastic fibers in the BATSM were continuous and intact, and had a clear continuity with the surrounding normal alveolar epithelium (D). Immunohistochemical basal results indicate basal cells diffusely positive for P40 (E) and luminal cells diffusely positive for TTF‐1 (F).

Figure S4: H&E staining and immunohistochemical of the MA. On the side adjacent to the alveolar lumen, columnar cells grow mixed with invaginated alveolar epithelium (A). Double staining for P40/TTF‐1 can confirm the coexistence of the two cell types (B). TTF‐1 staining is shown in brown, and P40 staining is shown in purple. Note: The red → represent the intermingled distribution of luminal columnar cells and type II alveolar epithelial cells near the alveolar lumen. The green * indicate columnar cells adjacent to the stroma.

Zhao S., Li J., Hou L., et al., “Pulmonary Metastasizing Ameloblastomas can Masquerade as Certain Bronchiolar Adenoma‐Like Tumor With Squamous Epithelial Metaplasia,” Pathology International 76 (2026): e70155. 10.1111/pin.70155.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.