Background and Clinical Significance: Histiocytic sarcoma is a rare and aggressive hematopoietic malignancy, which is particularly uncommon in the head and neck region and exceedingly rare within lymph nodes associated with salivary glands. The present study aims to describe the clinical, radiologic, histopathologic, and immunophenotypic features of a primary histiocytic sarcoma, arising in a lymph node within the submandibular gland, and to highlight the diagnostic challenges and management considerations through a correlation with the existing literature. Case presentation: This case report was conducted according to the CARE guidelines. A 93-year-old male presented with a progressively enlarging mass at the right submandibular region. Clinical examination, magnetic resonance imaging, and fine-needle aspiration cytology were performed, raising suspicion for a malignancy. The patient underwent surgical excision of the right submandibular gland with limited level I_b lymph node dissection. Histopathological evaluation combined with an extensive immunohistochemical panel established the diagnosis of histiocytic sarcoma. The tumor was composed of pleomorphic epithelioid and spindle-shaped cells with marked cytologic atypia and high mitotic activity. Immunohistochemistry demonstrated strong positivity for histiocytic markers (CD163, CD68, CD14) and negativity for epithelial, lymphoid, and dendritic cell markers, allowing for the exclusion of major differential diagnoses. The proliferative index (Ki-67) was approximately 90%, indicating aggressive biological potential. FDG PET-CT performed two months after surgery showed no evidence of residual, regional, or distant disease. Considering the localized presentation and the patient’s advanced age, no adjuvant therapy was administered. During follow-up, no evidence of recurrence or disease progression was observed. Conclusions: Primary histiocytic sarcoma involving a lymph node within the submandibular gland is extremely rare and may clinically and cytologically mimic other malignancies. Accurate diagnosis relies on comprehensive immunohistochemical evaluation and exclusion of phenotypic mimickers. A review of previously reported cases of cervical lymph node histiocytic sarcoma demonstrated an age range from 35 to 80 years, with a male predominance and a higher incidence in Asian countries. Most cases presented with localized cervical lymph node disease. Surgical excision was the most commonly applied treatment, and was frequently associated with favorable outcomes, with several patients remaining disease-free during follow-up periods ranging from 24 to 48 months. The accumulation of additional well-documented cases is essential to improve diagnostic accuracy and guide evidence-based treatment strategies for this uncommon entity.

Granular cell tumors (GCTs) are rare benign neoplasms that are most often located in the soft tissues of the extremities and chest wall. Malignant GCTs have also been reported. GCTs of the biliary tract are extremely rare, uncommon non-epithelial benign neoplasms that cause focal thickening of bile duct wall without mucosal invasion. They consist of polygonal cells with granular appearance and stain positive in S-100 protein, indicating a neural (Schwann cell) origin. We report our experience of a 57-year-old Caucasian woman who presented with obstructing jaundice due to a distal bile duct stricture highly suspicious of cholangiocarcinoma. A Whipple’s procedure was successfully performed, and the final pathology revealed a benign GCT of the distal bile duct. Whipple’s is an extremely radical procedure for such benign lesions and additional investigations, such as cytology sample, may result in a less aggressive approach as those tumors grow slowly and do not metastasize.