Spontaneous Infarction of Benign Salivary Gland Tumors: A Series of 5 Cases

ABSTRACT

Fine needle aspiration cytology (FNAC) is a commonly used rapid diagnostic modality for diagnosing salivary gland tumors. Accurate fine‐needle aspiration cytology diagnosis of salivary gland neoplasm can be challenging due to the presence of various metaplasia and infarction. Post‐FNAC infarction is a known phenomenon in salivary gland tumors; however, spontaneous infarction is a rare occurrence. Here, we report five cases of benign salivary gland neoplasms with spontaneous infarction, diagnosed on cytological examination. Clinical findings were recorded; cytological examination and histological correlation were performed, emphasizing the characteristic features suggestive of infarction in these cases. Changes related to infarction, such as the presence of metaplastic squamous cells, small atypical cells, bare nuclei, necrotic debris with inflammatory cells, should be paid attention to during cytological examination, and the possibility of infarction should be kept in mind before labeling such cases as malignancy. These features mask the characteristic morphology of benign salivary gland neoplasms, raising suspicion of malignant change, hence posing a cytological diagnostic challenge.

1. Introduction

Fine needle aspiration cytology (FNAC) is commonly used for diagnosing salivary gland tumors. These lesions may undergo infarction post‐FNAC; however, spontaneous infarction of these tumors without prior history of FNAC is rare. The cytopathological features of benign salivary gland tumors diagnosed by fine needle aspiration cytology are well established [1]. However, accurate diagnosis of salivary gland neoplasm on FNAC can still be challenging due to the presence of various metaplasia and infarction [2, 3]. Post‐FNAC infarction of benign salivary gland tumors like Pleomorphic adenoma and Warthin tumor has been documented; however, spontaneous infarction of these tumors is uncommon [4]. Few such cases have been documented in the literature. Infarction of benign salivary gland neoplasms poses a diagnostic challenge to cytopathologists, as the characteristic cytological features are altered due to the effect of infarction, and these cases could be misdiagnosed as malignant neoplasms. This can alter the management of these benign neoplasms and render unnecessary stress to the patient as well.

Here, we report five cases of benign salivary gland neoplasms with spontaneous infarction, diagnosed on cytological examination.

2. Material Methods

This is a retrospective observational study (Case Series) with a study period from 2023 to 2025. A total of 4608 FNAs were performed during this period. Out of these cases, 340 FNAs were done from salivary glands. We searched for the keywords salivary gland, benign, infarction, necrosis, metaplastic cells, bare nuclei on the HIS system (Hospital Information System) to search for such FNA cases that had infarction. We could retrieve five cases of benign salivary gland neoplasms that showed infarction on cytology smears in the form of necrosis, dirty background, presence of inflammatory cells, bare nuclei, and atypical‐looking squamoid cells. Four cases were diagnosed as Warthin tumor and one case as Pleomorphic adenoma. Clinical information was retrieved from cytopathology forms for each case. Prior to fine needle aspiration, each patient had undergone a thorough clinical assessment by a cytopathologist, including a detailed history taking and palpation of the mass. The cases that did not have a history of prior FNA were included. Duration of swelling, growth rate, consistency, mobility, tenderness, and overlying skin changes were recorded from the patient cytopathology forms. Cytology and Histopathology slides were reviewed by two Pathologists (AG & AZ). Histopathology slides were reviewed in these cases to confirm the diagnosis.

3. Case Series

Cytological features of five cases of benign salivary gland neoplasm with spontaneous infarction (Four‐Warthin tumor, One‐Pleomorphic adenoma) were reviewed.

3.1. Clinical Findings of the Cases

Out of these five cases, two were females and three were males, with age ranging between 54 and 75 years. Four were parotid swellings, and one was a submandibular swelling. All the cases had gradually progressive swellings, and three reported on and off pain and mild enlargement of swelling, which was of recent onset. Duration of swelling ranged from 1 to 8 years. On clinical examination, all the swellings were well circumscribed, firm in consistency, with sizes ranging between 2 and 8 cm in maximum dimension. All the cases were unilateral except one case, which was bilateral. None of the cases had a history of prior FNAC. There were no clinical signs of inflammation, facial palsy, or any palpable lymph nodes in any of the cases (Table 1).

TABLE 1‐.

Clinical and pathological features of the cases.

Case	Age (years)	Sex	Presenting symptoms/clinical examination	Laterality	Duration	Progression	Association with pain	Radiological findings	Cytological features	Diagnosis on cytology	Histological diagnosis (% of infarction and metaplasia)
1	75	F	Submandibular swelling‐ 4 × 4 cm, well‐defined, firm to hard, restricted mobility, complaints of pain for 5 months, Overlying skin‐ No signs of inflammation, No Facial Palsy, No Palpable lymph nodes	Left	8 years, became painful for the last 5 months	Gradual	Yes	CECT Neck‐ Around solid lesion, 4.6 × 4.6 × 5.4 cm in left submandibular region at junction of ramus and body of mandible, likely arising from parotid.	Moderately cellular, anucleate (ghost) squamous cells admixed with atypical‐looking viable squamous cells along with oval to elongated cells, necrotic background with fragments of chondromyxoid material	Category‐ IV ‐B: Infarcted Pleomorphic adenoma D/D‐ Malignant transformation	Pleomorphic Adenoma Infarction‐ 40% Squamous Metaplasia‐ 20%
2	54	M	Parotid swelling‐3 × 4 cm, well‐defined, firm, mobile, Overlying skin‐ No signs of inflammation, No Facial Palsy, No Palpable lymph nodes	Right	9 months	Gradual	Yes	HR‐USG: A well‐defined heteroechoic cystic lesion, 2.3 × 2.5 × 4.1 cm with internal septations involving the right parotid, likely lymphoepithelial cyst	Cellular, sheets of oncocytic cells with columnar metaplasia, along with squamous cells and lymphocytes on a dirty, necrotic background	Category‐ IV‐A: Warthin tumor D/D—Other squamous epithelial neoplasms	Warthin tumor Infarction‐ 20% Squamous metaplasia‐ 30%
3	59	M	Parotid swelling‐3 × 2 cm, well‐defined, firm, mobile, Overlying skin‐ No signs of inflammation, No Facial Palsy, No Palpable lymph nodes	Right	2 years	Gradual	No	Enlarged right parotid involving both lobes, with a large complex solid hypoechoic lesion with internal septations, likely Pleomorphic adenoma	Paucicellular smears, predominantly necrosis, inflammatory cells, and scattered metaplastic squamous cells, along with oncocytic cells	Category‐ IV‐A: Warthin tumor	Warthin tumor Infarction‐ 30% Squamous metaplasia‐ 15%
4	54	F	Parotid swellings, right‐ 8 × 7 cm, left‐2 × 2 cm, firm, diffuse, restricted mobility, Overlying skin‐ No signs of inflammation, No Facial Palsy, No Palpable lymph nodes	Bilateral	Right‐ 2.5 years Left‐ 1 year	Gradual	No	NA	Paucicellular, scattered oncocytic cells, with inflammatory cells, and cholesterol crystals on a necrotic background	Category‐ IV‐A: Infarcted oncocytic tumor likely Warthin's tumor	Warthin tumor Infarction‐ 20% Squamous metaplasia‐ 10%
5	63	M	Post aural swelling, 2 × 1 cm, firm to hard, well defined, restricted mobility, Overlying skin‐ No signs of inflammation, No Facial Palsy, No Palpable lymph nodes, History of fever present	Left	1 year	Gradual	Yes	NA	Paucicellular, predominantly necrosis, scattered oncocytic cells, few metaplastic squamous cells, with inflammatory cells	Category‐ IV‐A: Infarcted parotid neoplasm, likely Warthin tumor	Warthin tumor Infarction‐ 30% Squamous metaplasia‐ 10%

Abbreviations: CECT‐ contrast enhanced computed tomography, D/D‐ differential diagnoses, HR‐USG‐ high resolution ultrasonography.

The first case diagnosed as infarcted pleomorphic adenoma was categorized as Milan Category IV‐B in view of the presence of suspicious‐looking cells in a necro‐inflammatory background. Although in some fields of the smears, chondromyxoid fibrillary material and oval to elongated plasmacytoid cells could be seen, which indicated the possibility of pleomorphic adenoma that had undergone infarction (Figure 1). A possibility of malignant transformation couldn't be completely excluded. Hence, this case was categorized as Category IV‐B. This case was histologically confirmed as Pleomorphic Adenoma with areas of infarction (40%) and squamous metaplasia (20%). The second case was an infarcted Warthin tumor, which showed the presence of an abundant amount of mature‐looking metaplastic squamous cells, along with oncocytic cells in a dirty necrotic background (Figure 2). Hence, this was diagnosed as Warthin tumor with changes of infarction, categorized as Category IV‐A. However, in view of abundant squamous cells, the possibility of any other squamous neoplasm was kept in the differential diagnoses. Later, the resection specimen showed prominent squamous metaplasia (30%) in this case. The third case was a Warthin tumor, Category IV‐A, with predominant necrosis, inflammatory cells, and scattered metaplastic squamous cells, along with oncocytic cells. The last two cases, which were diagnosed as infarcted parotid neoplasms likely Warthin tumor, Category IV‐A, showed paucicellular smears with similar features. These cases were later confirmed histologically as Warthin tumor with areas of squamous metaplasia and infarction (Figure 2). We found moderate concordance between cytological and histological diagnosis, where the final diagnosis was similar in all the cases. However, there was suspicion of malignancy in two out of five cases, and in two cases, the diagnosis was given as infarcted oncocytic parotid neoplasms, with a possibility of Warthin tumor. These cases were later confirmed as Warthin tumor. This highlights the difficulty in arriving at a definite conclusive diagnosis on cytology in the case of infarction of these tumors.

FIGURE 1.

(a) MGG‐stained smears showing atypical‐looking squamoid cells in a necrotic background, 200×; (b) MGG‐stained smears showing clusters of oval cells embedded in a necrotic fragment, 200×; (c) MGG‐stained smear showing fragments of chondromyxoid material, 400×; (d) H&E‐stained smear showing metaplastic squamous cells in a necrotic background, 200×.

FIGURE 2.

(a) PAP‐stained smear showing metaplastic squamous cells on a dirty necro‐inflammatory background, 400×; (b) H&E‐stained section showing completely infarcted papillary structures with ghost outlines with underlying fibrocollagenous tissue, 200×. (c) H&E‐stained section showing a tumor with cystic spaces lined by metaplastic squamous epithelium filled with necro‐inflammatory exudates, 200×; (d) H&E ‐stained sections showing cystic space lined by tall columnar eosinophilic and oncocytic cells, surrounded by dense lymphoid infiltrate, 400×. H&E—Hematoxylin & Eosin, MGG‐ May‐ Grunwald Giemsa, PAP‐ Papanicolaou.

4. Discussion

FNAC has been proved to be a very useful tool in the preoperative diagnosis of salivary gland neoplasms. Cytopathological features of various salivary gland neoplasms have been well described and are categorized into different categories based on the Milan system for reporting salivary gland cytopathology. However, diagnosing these neoplasms on FNAC is challenging in the case of spontaneous infarction. In the current study, we have tried to summarize the clinical and cytological findings of five cases of salivary gland neoplasms with infarction, including Pleomorphic adenoma and Warthin tumor. We found that these neoplasms followed a gradual course with the recent onset of pain and increase in size in some, due to which the patient visited the hospital and underwent FNA in our department. On cytological examination, the presence of metaplastic squamous cells, necrotic background, and mixed inflammatory infiltrate were the consistent findings in these cases, which suggested infarction of these tumors. These features mask the characteristic morphology of these benign salivary gland neoplasms and raise a suspicion of malignant change. Hence, such cases are a cytological diagnostic challenge. Cytological features such as metaplastic squamous cells, small atypical cells, bare nuclei, necrotic debris with inflammatory cells should be paid attention to during cytological examination, and the possibility of infarction should be considered.

On reviewing the literature, we have found few studies about salivary gland neoplasms with infarction, which discussed the morphological features favoring infarction. Cobanoglu et al. reported a case of post‐FNAC infarction of a pleomorphic adenoma in a 44–year–old female who presented with a painless parotid mass. FNA smears showed spindle and round cells forming small clusters. Findings were diagnostic for pleomorphic adenoma. On histological examination, a well‐circumscribed pleomorphic adenoma with a large central infarction was noted. Residual viable tumor tissue was identified as a thin rim at the periphery of the tumor. However, cytology smears showed no necrosis, which supported the fact that the necrosis had developed after FNA [5].

Ito et al. reported a case of a 57‐year‐old Japanese female with persistent swelling in the right parotid region, and FNAC of the tumor was done, followed by resection. The cytology smears showed necrotic cell clusters of varying sizes in a necrotic background. Occasional viable cell clusters were observed having polygonal to spindle‐shaped squamoid cells with large round to oval nuclei and conspicuous nucleoli. These cells showed nuclear pleomorphism with fine chromatin. No neoplastic myoepithelial cells were observed. These cells were suspicious for malignancy. Histopathology slides revealed infarcted pleomorphic adenoma. They concluded that the presence of atypical squamous metaplastic cells in a necrotic background was a feature of infarcted Pleomorphic adenoma. These atypical squamous cells can have large nuclei with conspicuous nucleoli and exhibit pleomorphism [6].

Wang et al. retrospectively analyzed five histopathologically confirmed cases of spontaneous infarction of salivary gland neoplasms. In this study, the authors found that only two cases were correctly diagnosed as Pleomorphic adenoma. Two cases were reported as suspicious of malignancy, and one case was inconclusive [7]. FNAC material was noted to be milky‐white or brownish paste, with or without tissue fragments. Cytology smears showed necrotic debris and scattered pleomorphic small cells resembling ‘naked nuclei’, having hyperchromatic and irregular nuclei, along with atypical squamous metaplastic cells. Few ghost cells and eosinophilic cells with non‐atypical nuclei were also noted, in addition to tumor‐associated glandular epithelial cells, myoepithelial cells, lymphocytes, neutrophils, and other inflammatory cells. Mucinous or chondroid stroma was occasionally seen, or it was completely absent [7].

Similarly, cases of infarcted Warthin tumor have also been reported in the literature. Classic cytomorphological features of Warthin tumor include oncocytic epithelial cells, lymphocytes, and granular background material [8, 9]. Diagnostic accuracy of FNAs for this tumor diagnosis is > 95%, based on these cytological features [8]. False‐negative cases of Warthin tumor are often categorized as Atypia of unknown significance (AUS) or SUMP, according to the Milan system of reporting salivary gland cytopathology. The most common cause of the misclassification is squamous metaplasia or mucinous metaplasia [10]. As per an earlier meta‐analysis about Warthin tumor, the most common false‐negative cases were reported as cysts, Pleomorphic adenoma, and Mucoepidermoid carcinomas on cytological examination [11].

Diagnostic pitfalls of Warthin tumor include its variants, such as infarcted, metaplastic, or infected [11, 12]. In one study on Warthin tumors, its variants accounted for 6.2% of these tumors [13]. Some previous papers reported infarction of Warthin tumors following FNA. The possible cause of FNA‐induced infarction is postulated as direct injury of a blood vessel by the needle [13]. However, FNA is not the only factor for causing infarction in Warthin tumor or other salivary gland neoplasms, since some cases have been reported without any history of FNA [13, 14]. The underlying pathogenesis of spontaneous infarction of Warthin's tumor is not well understood. Several mechanisms of spontaneous infarction in pleomorphic adenoma have been proposed, including restriction of blood flow by a neoplastic mass, trauma, drug‐induced vasoconstriction, thrombo‐occlusive vascular changes, and systemic conditions (diabetes mellitus or myocardial infarction) [15, 16]. None of these mechanisms seems to be the sole causative factor.

Infarcted or metaplastic Warthin tumor can be confused with mucoepidermoid carcinomas. Differentiating between the two entities could be a challenging task in cytology. Kato et al. reported a case of Warthin tumor with spontaneous infarction with suspicion of malignancy on radiology, in a 66‐year‐old male [17]. US‐guided FNA was performed, but the cytological diagnosis was uncertain. It was clinically diagnosed as a primary malignant salivary gland tumor. The completely resected lesion showed yellow–brown fluid. The histological examination revealed metaplastic squamous epithelium caused by infarction adjacent to viable Warthin's tumors.

The current study was in concordance with previous literature. Metaplastic squamous cells, small atypical cells, bare nuclei, necrotic debris with inflammatory cells should be identified as features of infarction, and this possibility should be considered before labeling such cases as malignancy.

5. Conclusion

Cytological diagnosis of infarcted Pleomorphic adenoma or Warthin tumor is difficult; cytopathologists must consider the presence of atypical metaplastic squamous cells in benign salivary gland neoplasms as an indicator of possible infarction. In addition, necrosis in salivary gland aspirate may indicate spontaneous infarction of benign tumors like Pleomorphic adenoma or Warthin tumor, along with the possibility of malignant transformation. Clinical presentation and radiological imaging findings should be taken into account, which aid in concluding a cytopathological diagnosis. This comprehensive approach may provide clinicians with accurate preoperative cytological information and minimize unnecessary agony to the patients.

Funding

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

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.