Lymphomas are broadly classified into Hodgkin lymphoma and non-Hodgkin lymphoma based on the presence or absence of Reed–Sternberg cells [1]. Non-Hodgkin lymphoma commonly arises in lymph nodes but may also present at extranodal sites, reflecting its hematologic origin [2]. Glomus tumors are benign mesenchymal neoplasms arising from hyperplasia of these structures and are classified into solid glomus tumors, glomangiomas, and glomangiomyomas based on the relative proportion of smooth muscle and vascular components [3,4]. The occurrence of glomus tumors in the oral or perioral region is uncommon. Herein, we report a rare case of synchronous presentation of cutaneous cluster of differentiation 30 (CD30)-positive anaplastic large T-cell lymphoma and glomangioma involving the labial mucosa of the upper lip, highlighting its diagnostic challenges and clinical significance.

A 61-year-old woman presented with a mildly tender lump on the inner aspect of the upper lip. The patient gave a history of trauma to the upper lip following a fall approximately 2 years prior to presentation. She was a known case of hypertension and hypothyroidism with dyslipidemia and had been on regular medication for the past 10 and 6 years, respectively. No other relevant systemic illness was noted.

Intraoral examination revealed a mildly tender, non-ulcerated mucosal lump measuring approximately 7×4×2 mm on the inner aspect of the upper lip. The lesion was similar in color to the adjacent mucosa, non-bleeding on palpation, and showed no discharge. The patient reported that the lesion was initially small and gradually increased in size over a period of 4–6 weeks. Clinically, the lesion appeared nonspecific and did not suggest an underlying malignant or vascular pathology. Based on the clinical appearance, differential diagnoses including mucocele, vascular malformation, minor salivary gland neoplasms (such as pleomorphic adenoma), and traumatic fibroma were considered.

Computed tomography (CT) of the face (plain and contrastenhanced) revealed a peripherally enhancing, centrally hypodense lesion measuring approximately 4.0×7.0 mm in the mucosal/submucosal region of the upper lip. The lesion was confined to the upper lip with no intranasal extension and no evidence of erosion of the maxillary alveolus (Fig. 1). The radiological impression favored an infective granuloma, and histopathological correlation was advised. In the present case, contrast-enhanced imaging demonstrated a localized soft-tissue lesion confined to the upper lip, corresponding to the clinically visible swelling, without radiologic evidence of a second distinct mass. However, preoperative CT imaging could not distinguish between the lymphomatous and vascular components. In retrospect, the peripheral enhancement pattern may reflect the vascular nature of the glomangioma, but definitive characterization of the two distinct lesions was achieved only through histopathologic examination.

Routine blood investigations, including complete blood count, erythrocyte sedimentation rate, and serum biochemistry, were within normal limits. The mucosal lesion was excised under local anesthesia. Intraoperatively, the superficial lesion appeared irregular at its base and lacked clear demarcation from the surrounding submucosal tissue. During further exploration of the surgical field, a second, well-circumscribed lesion was identified in a deeper submucosal plane, spatially distinct from the primary lesion and without gross evidence of infiltration. Both specimens were submitted separately for histopathological examination. Histopathological examination of the first excised specimen revealed a uniform proliferation of medium- to largesized atypical lymphoid cells with abundant amphophilic to eosinophilic cytoplasm, vesicular nuclear chromatin, and small basophilic nucleoli (Fig. 2). Numerous mitotic figures and focal areas of necrosis were identified. On immunohistochemistry, the tumor cells showed strong membranous and cytoplasmic positivity for CD30 and CD4, with negativity for CD20, PAX5 (paired box protein 5), and ALK-1 (anaplastic lymphoma kinase 1), consistent with a diagnosis of cutaneous CD30-positive anaplastic large T-cell lymphoma (Fig. 3). Histopathological examination of the second, deeper excised specimen demonstrated a distinct vascular proliferation composed of irregular, dilated vascular channels lined by flattened endothelial cells and surrounded by sheets of monotonous, bland round-to-oval cells with eosinophilic cytoplasm (Fig. 4). No cytological atypia, mitotic activity, or necrosis was observed. The uniform cytomorphology, perivascular arrangement, and absence of lymphoid atypia clearly distinguished this lesion from the superficial lymphoma component and were consistent with glomangioma. Importantly, no histologic admixture between the two components was identified. Histopathological examination of the first excised specimen confirmed cutaneous CD30-positive large Tcell lymphoma. Examination of the separately excised deeper specimen revealed features consistent with glomangioma. Based on the clinical, histopathological, and immunohistochemical findings, a final diagnosis of cutaneous CD30-positive anaplastic large T-cell lymphoma associated with glomangioma of the upper lip was established.

Following confirmation of non-Hodgkin lymphoma, the patient underwent comprehensive systemic evaluation. Positron emission tomography-CT performed as part of the staging protocol revealed localized disease with no evidence of regional or distant lymphadenopathy, organ involvement, or metabolically active lesions elsewhere. Bone marrow biopsy further confirmed the absence of disseminated disease. The patient was referred to the haemato-oncology department. Complete surgical excision was followed by four cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, which were well tolerated without significant complications. At 36 months of follow-up, the patient demonstrated complete clinical resolution without evidence of recurrence (Fig. 5). Functional and aesthetic outcomes were satisfactory.

The presence of a benign lesion alongside a malignant process has significant clinical implications, as it may mask the underlying malignancy and delay definitive diagnosis. In this case, the lesion presented as a mildly tender, non-ulcerated swelling of the labial mucosa with no burning sensation, numbness, cervical lymphadenopathy, and lack of tooth mobility and a benign clinical appearance. There was no bone destruction or alveolar bone involvement. Based on the clinical appearance, several differential diagnoses were considered prior to histopathologi-cal analysis. The history of trauma and lesion location suggested mucocele as a clinical consideration. However, the lack of bluish discoloration and slightly firm in consistency made the diagnosis less certain. A hemangioma was also considered considering the location of the lesion and rich vascular supply in the anatomic region, but lack of vascular appearance, diascopy negative (no blanching on pressure), absence of pulsatility or bleeding ruled out hemangioma as a diagnosis. Minor salivary gland tumors, particularly pleomorphic adenoma were considered as they are abundantly present in the labial mucosa. However, lack of lobulation or nodular appearance did not raise the suspicion. A traumatic fibroma was considered as a differential diagnosis due to its firm consistency and typical well-circumscribed nature.

The synchronous occurrence of two histogenetically unrelated tumors in the same anatomical site is exceptionally rare. In the present case, the simultaneous involvement of the upper lip by a CD30-positive large T-cell non-Hodgkin lymphoma and a glomangioma represents an unusual diagnostic entity, particularly within the craniofacial region. The lymphoid neoplasm was classified according to the World Health Organization Classification of Tumors of Hematolymphoid Tissues, 5th edition, which defines CD30-positive large T-cell lymphomas based on their characteristic histomorphology and immunophenotypic profile [5].

Synchronous neoplasms involving lymphoid malignancies are most often reported in association with epithelial tumors or other hematologic disorders. The coexistence of lymphomas with benign mesenchymal or perivascular tumors, such as glomangiomas, is exceedingly uncommon. In terms of demographics, the average age of presentation for non-Hodgkin lymphoma and oral glomus tumors is reported to be 50–55 years and approximately 45 years, respectively, with lymphomas showing a male predominance and glomus tumors an equal sex distribution. Our patient, a 61-year-old woman, falls within the expected age range but differs in sex and lesion site [6,7].

Approximately 40% of non-Hodgkin lymphoma presents at an extranodal site and 2%–3% of extranodal non-Hodgkin lymphoma arise primarily in the jaws and oral cavity. The most common site for an extranodal non-Hodgkin lymphoma in maxillofacial region is Waldeyer’s ring [7]. The intraoral sites for glomangiomas include the palate, tongue, buccal mucosa, gingiva, oropharynx, pterygoid fossa, and the parotid. The labial mucosa would be considered a rare site for occurrence of both cutaneous CD30-positive large anaplastic T-cell lymphoma and glomangioma.

The most common group of primary cutaneous T-cell lymphomas are mycosis fungoides while the second most common group is primary cutaneous CD30+ lymphoproliferative disorders. This group consists of primary cutaneous anaplastic large cell lymphoma (pcALCL), lymphomatoid papulosis and borderline tumors. The borderline tumors have clinical and histopathological features resembling the two [8]. Nearly 14% of all primary cutaneous T cell lymphomas (CTCL) are comprised of primary cutaneous CD30-positive large T-cell lymphomas while primary cutaneous anaplastic CD30+ cell lymphoma belongs to the subgroup of peripheral T-cell lymphomas. The prognosis of isolated skin lesions in the absence of any nodal disease has a favorable outcome. Primary cutaneous CD30 positive large T-cell lymphomas (PCLCL) are determined by the presence of CD30-positive cells. The CD30-positive cells could be either pleomorphic or anaplastic and have a wide spectrum with variation in their nuclear appearance along with cytoplastic abundance. The aid to distinguish PCLCL from other CTCL are use of antigenic markers. These lymphomas have an aberrant CD4 phenotype and strongly CD30 positive in immunohistochemistry [9].

Among the glomus tumors, the solid type (75%) is a true neoplasm whereas glomangioma and glomangiomyoma are malformations of normal glomus bodies. Glomangioma is a benign vascular variant of glomus tumor composed of dilated vascular channels surrounded by uniform glomus cells. It most commonly affects the extremities and is rarely reported in the oral or perioral region. The lesion is typically well circumscribed and may show contrast enhancement on imaging due to its vascular architecture. There is no evidence of literature documented regarding the recurrence of a glomus tumor of oral cavity. However, if there is evidence of recurring lesion, surgical excision is usually the choice of treatment.

Surgically, glomangiomas are typically well circumscribed, non-infiltrative vascular lesions that can be managed with complete local excision. In the present case, the lesion was not grossly distinguishable from the overlying lymphomatous component and was identified only on histopathologic examination. Complete excision was achieved without the need for further surgical intervention [4].

A combination of treatment options used for management of non-Hodgkin lymphoma are chemotherapy, radiotherapy, and surgery. The role of surgery is for purpose of an excisional biopsy and control of recurrent disease in a localized area by excision. In an aggressive lesion, radiotherapy can be used as an adjuvant. The treatment for extracutaneous cases (pcALCL) along with N1 peripheral lymph nodes is multi-drug regimen of chemotherapy-CHP (cyclophosphamide, doxorubicin, prednisone) or CHOP (CHP + vincristine) regimen [9]. In the present case, excisional biopsy was followed by multi-agent chemotherapy. The patient remained disease-free during a 36-month follow-up period, supporting the effectiveness of early diagnosis and appropriate oncologic management.

A review of the English-language literature revealed no previously reported cases describing the concurrent presentation of a CD30-positive large T-cell lymphoma and a glomangioma in the upper lip, highlighting the uniqueness of this case [4,10-14].

Two pathogenetic mechanisms may be considered in cases of synchronous tumors: collision tumors and composite tumors. Collision tumors are defined by the coexistence of two histologically distinct neoplasms arising independently in proximity, whereas composite tumors demonstrate intermingling of different tumor cell populations derived from a common progenitor or pathogenetic pathway. In the present case, the distinct histopathological and immunohistochemical features, along with the absence of transitional areas between the lymphoma and glomangioma components, favor the diagnosis of a collision tumor rather than a composite neoplasm. The synchronous presentation may therefore represent a coincidental occurrence rather than a shared etiopathogenesis [13].

Clinically, prior reports often described lymphoma lesions with overt features such as nodal involvement or ulceration, whereas our case presented as a benign-appearing, mildly tender, non-ulcerated labial swelling without cervical lymphadenopathy or bone involvement. Histopathology and immunohistochemistry confirmed a CD30-positive large T-cell lymphoma coexisting with a glomangioma, and the absence of transitional areas supports a collision tumor mechanism.

This case underscores the importance of maintaining a high index of suspicion and performing thorough histopathological and immunohistochemical evaluation of all excised lesions, even when clinical features suggest a benign process. Early and accurate diagnosis is crucial for appropriate oncologic management, prognostication, and follow-up. The rarity of this synchronous presentation underscores the need for heightened diagnostic vigilance and contributes valuable insight to the existing literature on unusual tumor associations in the oral and maxillofacial region.