Clinical context and complex differential diagnosis

Oral pyogenic granuloma (PG) is a frequent reactive lesion on the gingiva (83% of cases), but its manifestation on the buccal mucosa is exceptional, representing only 0.8% of intra-oral locations. In elderly patients, rapid growth associated with surface ulceration can closely simulate malignant vascular tumors, such as angiosarcoma or Kaposi's sarcoma. This clinical ambiguity makes the histopathological diagnosis particularly perilous, as illustrated by this case initially reported as an "atypical vascular tumor" in a 69-year-old woman.

Study objectives and hypotheses

The objective of this case presentation is to document the rigorous diagnostic approach required to identify a buccal GP and to highlight the decisive role of immunohistochemistry (IHC) in differentiating benign endothelial proliferations from infiltrating neoplasms. The study examines the hypothesis that the anatomical site influences not only the clinical presentation but also the biological behavior of the lesion. The authors compare the buccal GP to its gingival counterpart to determine whether the extragingival location is associated with a more favorable prognosis, particularly in terms of recurrence — a risk estimated between 3% and 23% for gingival lesions, but for which documentation is lacking for buccal locations.

Diagnostic approach and analytical protocol

This case report details the clinical management and anatomopathological analysis of a nodular lesion of the buccal mucosa in a 69-year-old female patient. The investigation protocol was structured to rule out any vascular malignancy in the face of rapid terminal growth of the lesion (1 month) following occlusal trauma.

The methodology employed includes the following steps:

• Surgical procedure: Excisional biopsy performed under local anesthesia. As a precautionary measure, daily aspirin was discontinued 7 days prior to the procedure. Hemostasis was achieved through conventional local measures.
• Tissue preparation: The excised specimen, measuring 1.2 × 1.0 × 0.5 cm, was formalin-fixed, paraffin-embedded, and then sectioned for Hematoxylin and Eosin (H&E) staining.
• Immunohistochemical panel (IHC): In order to differentiate pyogenic granuloma (PG) from malignant tumors (angiosarcoma, Kaposi's sarcoma), specific labeling was performed for:
  • CD31 and CD34: confirmation of the vascular lineage.
  • D2-40: exclusion of a lymphatic phenotype.
  • S100 protein: identification of perilesional nerve bundles.
  • HHV-8: screening for the virus associated with Kaposi's sarcoma.
  • Ki-67 and p53: evaluation of the proliferation index and gene expression profile.
• Clinical follow-up: Postoperative monitoring was maintained over a 9-month period to assess the risk of recurrence despite margins initially declared as involved.

Clinical presentation and histopathological analysis

The case reports a lesion in a 69-year-old female patient located on the left lower buccal mucosa, near the labial commissure. Initially stable for two years following the placement of mandibular implants, this 1.0 cm diameter sessile nodule showed rapid terminal growth following occlusal trauma (accidental biting). Clinically, the mass was pinkish-red in color, compressible, and prone to bleeding during manipulation, with focal central ulceration.

L'examen histopathologique après biopsie excisionnelle (spécimen de 1,2 × 1,0 × 0,5 cm) a révélé une prolifération lobulaire de vaisseaux de calibre capillaire sous un épithélium pavimenteux stratifié hyperplasique. Les capillaires, remplis de sang, étaient bordés par des cellules endothéliales proéminentes au sein d'un stroma fibromyxoïde œdémateux contenant un infiltrat inflammatoire mixte (lymphocytes et neutrophiles).

Immunohistochemistry (IHC) results

IHC analysis was decisive in ruling out differential diagnoses of malignant vascular tumours (angiosarcoma, Kaposi's sarcoma):

Epidemiological and comparative data

The synthesis of the literature data included in the study highlights the specificity of the buccal location compared to the classic gingival location:

• Anatomical distribution: In the largest reported series (293 cases), the gingiva accounts for 83% of locations compared to only 0.8% for the buccal mucosa.
• Etiology: Unlike gingival pyogenic granulomas (PG) associated with calculus or dental devices, extragingival lesions are almost exclusively attributed to bite trauma.
• Prognosis: While the overall recurrence rate of oral PG ranges between 3% and 23% (data dominated by gingival sites), no recurrence has been documented for cases localized on the buccal mucosa in the reviewed literature.

An atypical and misleading buccal localization

Pyogenic granuloma is a common reactive lesion, but its site is overwhelmingly gingival (83%). Localization in the buccal mucosa, as in this 69-year-old patient, represents only 0.8% of cases. This rarity, coupled with rapid growth following occlusal trauma (biting) and advanced age, can wrongly lead the practitioner toward malignant vascular pathologies. In this study, the 1 cm lesion, initially stable for two years after implant placement, suddenly increased in volume, clinically and histologically mimicking an angiosarcoma or Kaposi's sarcoma due to marked endothelial proliferation.

Immunohistochemistry: the indispensable arbiter

The definitive diagnosis was based on a precise immunohistochemical profile. While CD31 and CD34 markers confirmed the vascular origin, the absence of staining for HHV-8 allowed for the exclusion of Kaposi's sarcoma. Furthermore, the absence of cytological atypia, the preservation of perilesional nerve bundles (S100 staining), and a low Ki-67 proliferation index invalidated the hypothesis of a malignant tumor. Notably: although the margins of the excisional biopsy were reported as involved, the initially deferred re-excision was ultimately not performed due to the benign nature confirmed by additional analyses.

Prognosis: an anatomical specificity?

The study suggests a behavioral distinction between gingival PG and buccal PG. While gingival recurrence varies from 3% to 23% (often linked to persistent irritants such as calculus or ill-fitting appliances), no recurrence has been documented for lesions of the buccal mucosa. Here, the outcome was favorable without further intervention. This difference in prognosis could be explained by the absence of chronic irritants inherent to the gingival site, facilitating complete healing after simple excision, although follow-up remains the rule.

Study limitations

This is a single case report (n=1) documenting a rare location. Although the authors rely on a series of 293 cases for prevalence statistics, data specific to the buccal mucosa remain limited to about a dozen cases in the English-language literature. Generalizing the low recurrence rate for this specific site therefore requires larger cohort studies to confirm this clinical trend.

In concrete terms, for the practitioner:

• Diagnostic vigilance: Do not exclude pyogenic granuloma when faced with a rapidly growing exophytic lesion in elderly subjects; however, biopsy with immunohistochemistry (CD31, CD34, HHV-8) is essential to rule out angiosarcoma or Kaposi's sarcoma.
• Prognosis by site: Note that the risk of recurrence is significantly lower for buccal locations (close to 0% in the literature) compared to classic gingival locations (3% to 23%).
• Management: In cases of confirmed PG diagnosis on the buccal mucosa, clinical monitoring may be preferred over aggressive re-excision, even if the pathology report mentions involved margins.

Technical lexicon of the study

Pyogenic granuloma (PG): Benign reactive capillary proliferation, also named lobular capillary hemangioma, typically occurring in response to local irritation or trauma.

Lobular capillary hemangioma: Histological term synonymous with pyogenic granuloma, describing an architecture organized into lobules of capillaries lined with plump endothelial cells.

CD31 and CD34: Immunohistochemical surface markers expressed by endothelial cells, used to confirm the vascular origin of cell proliferation.

HHV-8 (Human Herpesvirus 8): Pathogen associated with Kaposi's sarcoma; its negative detection by immunohistochemistry allows for the exclusion of this malignant pathology.

Ki-67 proliferation index: Nuclear marker evaluating the fraction of cells in the division phase; a low index is a major diagnostic argument against angiosarcoma.

S100 protein: Immunohistochemical marker used to identify nerve bundles; their preservation at the periphery of the lesion indicates non-infiltrating growth.

D2-40: Lymphatic endothelium-specific monoclonal antibody, used to differentiate hemangiomatous proliferation from a lymphatic phenotype.

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