Unilateral synchronous masses of the neck revealing a malignant Carotid Body Tumor: A case report and literature review

Abstract

Introduction and importance

Paraganglioma (PG); also known as Glomus Tumor, is a rare neoplastic entity that originates from neural crest cells. It can manifest in different patterns, chiefly benign but others are locally invasive and malignant in behavior. Due to the prevalence of other more common types of neck masses and Paraganglioma's exceeding rarity, misdiagnoses can easily take place, and this results in higher patient morbidity and mortality rates. Preoperative diagnosis constitutes a major clinical challenge, especially in patients with a previous surgical history in the neck region like our patient.

Case presentation

We are hereby presenting the case of a 56-year-old female with a known history of total thyroidectomy, who presented to our department with a progressively growing painful recurring neck mass two years following her total thyroidectomy. The preoperative diagnostic assessment revealed two unilateral synchronous masses encapsulating the Right Common Carotid Artery and occupying the common carotid bifurcation.

Clinical discussion

Complete surgical resection of the lesions after isolation from the surrounding anatomical structures was done. Subsequent histopathological and immunohistochemical analyses of the specimens established the diagnosis of a Carotid Body Tumor (CBT).

Conclusion

CBTs are rare vascular neoplasia, and they possess the potential for malignant transformation. This neoplasia warrants investigation and documentation to establish innovative diagnostic parameters and accomplish timely surgical interventions. To the best of our knowledge, this is the first documented case of a unilateral synchronous malignant Carotid Body Tumor from Syria. Surgery remains the treatment of choice, while radio-/chemotherapy is reserved for non-surgical cases only.

Highlights

• •Paragangliomas are extremely rare tumors and comprise less than 0.012 % of all human neoplasia.
• •Paragangliomas do not constitute more than 0.6 % of all presenting neck masses. Synchronous unilateral PGs are even rarer.
• •CBTs comprise 6–10 % of malignant neck masses. Early diagnosis facilitates treatment and minimizes potential complications.
• •Definitive diagnosis is reached via histopathology accompanied with immunohistochemical analysis.
• •Surgical resection is the treatment of choice for Carotid Body Tumors while radiotherapy is reserved for inoperable cases.

1. Introduction

Paraganglioma (PG) is classically a benign non-secretory neoplasm that originates from the sympathetic/parasympathetic nodules and other neural crest cellular structures in the human body [1]. PGs account for less than 0.012 % of all neoplastic entities that affect humans [2], and it does not exceed 0.6 % of all occurrences of neck masses. Furthermore, PG is extremely rare and favors occurring in the 5th decade of life in females with a female-to-male predominance rate of 1.5–2:1 [3]^, [4]. On the other hand, malignant PGs have an equal distribution among males and females.

Most PGs have been of sporadic origin. However, familial, and hereditary etiologies have accounted for almost 10 % of reported cases [4].

Carotid Body Tumor (CBT) is the most prevalent neck Paraganglioma, and accounts for 65 % of such masses, and comprises 6–10 % of the malignancy rate [5]. It is due to normal carotid body cell hyperplasia, rather than a true neoplastic lesion. It spores from the dorsal aspect of the Common Carotid Artery bifurcation and causes compressive symptoms as it expands. The extent of growth, adjacent organ involvement, and nodular metastasis are crucial malignancy determinants, because the clinical features are more important predictive factors [6].

Diagnostic evaluation relies on comprehensive clinical examination accompanied by wise judgement regarding the mass' characteristics, such as the unique anatomical location, vertical stability, horizontal movement, bruit heard via stethoscope, and insidious growth [7]. Adjunct evaluation is needed and comes in the form of colored Doppler Ultrasound (DUS), Computed Tomography Angiogram (CTA), and Magnetic Resonance Imaging (MRI). They aid in lesion localization, determining neural involvement, and depicting the extent of the tumor [8]. Laboratory investigations contribute to the establishment of a diagnosis and determine even rare types of PGs that are of secreting nature [9].

Total resection is the gold standard treatment method that results in minor complications [5], while radiotherapy is reserved mainly for inoperable and highly comorbid cases [10].

The work has been reported in line with the SCARE criteria and the revised 2020 SCARE guidelines [20].

2. Presentation of case

Herein, we present the case of a 56-year-old female with a known history of total thyroidectomy 2 years prior. The patient's chief complaint was a sudden and progressively slow-growing slightly tender right-sided neck mass for 1 year. With the passing of time, the patient started experiencing local tenderness felt upon palpating the mass. Symptoms were also accompanied by progressive dysphagia only to solids and mild hoarseness of voice. The patient did not experience any trauma to the area of the lesion, syncopal episodes, altered mental status, difficulty in neck movement, or dyspnea. Furthermore, the occurrence of orthopnea, paresthesia, and overlying skin changes like redness, ulceration, or hypo-/hyperpigmentation was denied.

B-symptoms like fever, night and/or cold sweats, and unintentional weight and/or appetite changes were also denied. Moreover, she also denied any exposure to carcinogenic and/or arsenic compounds.

Her previous surgical history solely included total thyroidectomy. Findings of the post-thyroidectomy histopathological analysis revealed a Follicular Adenomata with nodular Goiter. No signs of metastases or lymph node involvement were seen.

The patient's previous medical history includes Diabetes Mellitus type II and postoperative hypothyroidism.

Her drug history was comprised of Metformin and Levothyroxine.

Her family, allergic, and psychosocial histories were negative.

Her Body Mass Index was 30 kg/m².

The clinical examination began by taking the patient's vital signs which were within acceptable limits.

Physical examination of the right side of the neck revealed the following: Via inspection, a skin bulge was evident extending along the anterior right neck triangle causing bulging of the superficial jugular vein. The overlying skin did not reflect signs of local inflammation. Horner's sign was negative, and the mass did not move with swallowing.

Via palpation, there were two separate, solid, and well-defined masses that were unattached to the overlying skin. The lower mass was located at the thoracic outlet, with its upper margin parallel to the neck's Kocher incision scar, while the upper mass was located below the right mandibular angle. No regional nor axillary lymphadenopathy was detected.

Via auscultation, an audible murmur was heard over the upper mass only.

The examination findings of the left side of the neck were unremarkable.

A complete laboratory panel was done and yielded the following relevant results; (HbA1C: 8.7 %), clinical hyperthyroidism caused by Thyroxine intake was noted (TSH: 0.1 mIU/L, FT4: 1.89 ng/dL, T3: 0.89 ng/dL). Serum Cortisol was within normal (12 nmol/L at 8 A.M). Systemic inflammatory response parameters were normal (ESR: 18 mm/h, CRP: 0.5 mg/dL, WBCs: 7000/μL). Finally, a urine 24 h collection for nor-metanephrine and metanephrine revealed normal values of (198 μg/24 h and 495 μg/24 h), respectively.

Diagnostic assessment: Doppler Ultrasound of the neck revealed two unilateral separate and highly perfused neck masses. Caudally, a (30 × 40 mm) mass was encapsulating the Right Common Carotid Artery (R-CCA) anteromedially, while the cranial mass measured (35 × 50 mm) occupying the right carotid bifurcation reflecting an obvious Lyre sign. The carotid blood flow was normal with no plaques detected on DUS.

A total body contrast-enhanced Multi-Slice Computed Tomography (MSCT) scan was then carried out, and its findings conformed with those of the DUS. It confirmed the position and extent of the two unilateral synchronous neck masses as well as excluding other synchronous Paragangliomas or metastases (Fig. 1A-B-C).

Fig. 1.

A: Preoperative MSCT image in axial view showing a mass (Blue Arrow) amidst the right carotid artery bifurcation.

B: Preoperative MSCT image in sagittal view showing the masses in the region of R-CCA.

C: Preoperative MSCT image in coronal view showing the masses in the region of R-CCA. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Preoperative steps were taken to optimize the patient for surgery, such as keeping her at a nil-per-mouth status, establishing intravenous access, and administering preoperative prophylactic antibiotics.

Notable challenges was the unavailability of genetic typing at the time.

Therapeutic intervention: Based on the previous clinical elements, a surgical intervention was warranted. The surgery was successfully performed under general anesthesia with no perioperative complications at our tertiary university hospital by two Vascular Surgery specialists with 15 years of experience each. A longitudinal incision along the anterior border of the sternocleidomastoid muscle was done to achieve optimal surgical exposure. We entered via the platysma muscle and noticed the tortuousness of the superficial jugular vein as it was compressed by the caudal mass. Dissecting the omohyoid muscle revealed a solid encapsulated mass surrounding the R-CCA. Entering the carotid sheath, a combination of blunt and sharp dissection allowed the identification and isolation of the vagus nerve between the common carotid artery and the internal jugular vein. The mass oozed blood upon manipulation but successful hemostasis was swiftly achieved. Furthermore, peri-adventitial dissection of the anterior surface of the R-CCA to its bifurcation revealed the upper mass where proper control and ligation of the facial vein took place. As the bifurcation was detected, we bypassed the mass to control the Internal Carotid Artery (ICA), but preservation of the External Carotid Artery (ECA) was difficult due to heavy adhesions (Shamblin II). Finally, ECA was divided at its origin and was successfully ligated distal to the mass, while the corresponding arterial defect was repaired with two separate monofilament polypropylene sutures (Fig. 2A-B-C-D).

Fig. 2.

A: Postoperative image after resection of the upper (cranial) mass.

B: Postoperative image after resection of the upper (caudal) mass.

C: Intraoperative image after dissecting the mass free of the right internal carotid artery the right internal carotid artery ICA, the sutures used due to dissecting the external carotid artery along with the mass. Green Arrow marks the internal carotid artery, the Blue Arrow marks the common carotid artery, and the Yellow Arrow marks the 12th cranial (Hypoglossal) nerve.

D: Intraoperative image after dissecting after dissecting the caudal mass of the R-CCA. Blue Arrow marks the common carotid artery, the Purple Arrow marks the external jugular vein, the Green Arrow marks the internal jugular vein, and the Yellow Arrow marks the vagus nerve. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

The two resected lesions were directly sent for detailed histopathological analysis.

Histopathological analysis through Hematoxylin and Eosin (H&E) staining demonstrated two partially encapsulated masses measuring (3.3 × 3 × 1 cm) and (3.5 × 2.5 × 1.5 cm) respectively. The first one was comprised of hemorrhagic heterogenous pigmented tissue, whereas the second was of white pale heterogeneous tissue. Both masses were consistent with the diagnosis of Carotid Body Tumor (Fig. 3). Further analysis via Immunohistochemistry (IHC) analysis was achieved and it reported the following results: NSE and Synaptophysin stained positive, whereas CD34/TTF-1 stained negative (Fig. 4A-B-C-D).

Fig. 3.

Histopathological analysis via H&E staining of the resected lesions conformant with traits of Carotid Body Tumor.

Fig. 4.

A: IHC analysis of the resected specimens staining positive for Synaptophysin.

B: IHC analysis of the resected specimens staining positive for Neuron Specific Enolase (NSE).

C: IHC analysis of the resected specimens staining negative for CD34.

D: IHC analysis of the resected specimens staining negative for Thyroid Transcription Factor-1 (TTF-1).

Our patient was discharged to the outpatient setting within 5 days of her operation. Her symptoms significantly subsided after surgical intervention. During her hospital stay, sterile applied wound dressings for the wound, proper fluid administration, analgesics, and prophylactic antibiotics to control the postoperative pain were all steps taken to facilitate recovery. She was scheduled regular follow-up visits at the 1 month, 6 months, and 12-month mile marks. During the follow up period, she was examined clinically and underwent thorough radiological imaging. The results of which were all normal with no signs of tumor remains, recurrence, or metastasis.

She was also referred to a specialized oncology clinic for proper follow-up protocol adherence.

3. Discussion

CBTs comprise 60 % of head and neck PGs. Multiple confirmed etiological factors include genetic inheritance and female gender, whereas hypothesized factors include high altitude -over 1500 m- and chronic hypoxia [1].

CBTs are either functioning or non-functioning. Patients with non-functioning CBTs are typically asymptomatic and such CBTs are slow-growing masses that adhere to adjacent cranial nerves and result in neural compressive symptoms for the affected patients [11]. On the other hand, functioning CBTs secrete chromaffin and result in symptoms conformant with the subsequent endocrine system dysfunction, such as hypo-/hypertension and in rarer cases, flushing seizures [12].

The gold standard noninvasive technique to assess mass vasculature, extent, and concomitant atherosclerosis is Duplex Ultrasound. Other preoperative diagnostic modalities include Computed Tomography (CT) and magnetic resonance techniques like MRI and Magnetic Resonance Angiography (MRA) which are utilized to determine the extent of tumor involvement and the potential presence of accompanying tumors and metastases. Modern radiological diagnostic methods, such as CT and Positron Emission Tomography (PET) scans hold the superiority in detecting malignant and benign CBTs, as well as metastasis. On the other hand, invasive techniques like the angiogram are preserved in CBTs, especially when embolization or other endovascular procedures are considered (The Matas test) [13].

Timely surgical intervention is the cornerstone treatment for CBTs. In terms of tumor predictors, tumor size and Shamblin classification aren't exclusive predictors of malignancy or recurrence especially when Succinate Dehydrogenase (SDH) mutations are positive. Moreover, SDH mutations should be investigated in all CBT patients as it may modulate therapeutic strategies as well as patient follow-up [14]. High morbidity ensues when CBTs are inoperable and such patients are therefore referred to undergo radio-/chemotherapy [3].

Another treatment modality that is considered first-line therapy in certain cases is External Beam Radiation Therapy (EBRT). It results in satisfactory tumor control results in elderly comorbid patients [10]. Nonetheless, it did not improve survival rates over the past two decades [15].

Malignant transformation of CBTs is confirmed after histopathological analysis but nevertheless suspected clinically regarding tumor behavior [16]. CBTs rarely metastasize. However, when they do, it is primarily towards the lymph nodes [4]^, [17]. Other potential metastatic locations include the brain, pulmonary tissue, bone, and liver [1]^, [18]^, [19].

It was extremely rare to find a case that involved a unilateral synchronous PG occurrence. Therefore, for the purposes of literature review and to depict how rare our case is, we reviewed published literature in the last 10 years (2012-2022) about CBTs in PubMed English. During our review, we focused on malignancy and recurrence. 25 retrospective studies, 17 case reports, and 3 systematic reviews -those 3 weren't included in the following literature review- were elected out of 204 available papers by applying the following keywords in our search engine (Carotid Body Tumor, malignant or metastatic) and (Carotid Body Tumor/surgery “Mesh”). The inclusion criteria included English language, surgical resection, and malignancy confirmed or excluded by histology. On the other hand, we've excluded reports of non-English language and those that did not indicate malignancy (Table 1).

Table 1.

This table summarizes our review of the literature.

	N		%
Patients	1753		–
Asian	1014		57.8
Tumors	1809		–
Female	1144		65.4	94.9
Male	519		29.6
Side 75 %
Right	540		29.9
Left	500		27.6
Bilateral	282		15.6
Shamblin 87 %
I	328		20.8
II	665		42.2
III	581		36.9
Characteristics
Asymptomatic mass	928		52.9
Confirmed malignancy N = patients 67	Lymph nodes	44	–
	Pulmonary metastasis\lymph nodes	9
	Brain	2
	Vertebral	1
	bone	4
	Mediastinum	1
	Liver	1
	Systemic	2
	Local invasion	2
	Histology determined	1
SDH mutation	68		–
Recurrence	30		1.71

Literature originating from Asia were dominating the scene during this past decade with 24 papers. Out of 1753 patients and 1809 tumors, a 57.8 % Asian origin were documented, and the female-to-male predominance ratio was 2.2:1 (65.3 % vs. 29.6 %). Furthermore, 1574 out of the 1809 tumors were documented and constituted 87 % were graded by the Shamblin classification (Grade I 20.8 %, Grade II 42.2 %, and Grade III 36.9 %).

As for tumor location, it was obtained in only 73 % (29.9 % right-sided, 27.6 % left-sided, and 15.6 % were bilateral).

Regarding patient presentation, patients mostly presented with an asymptomatic mass as this was reported in 52.9 % of patients.

In terms of age groups, the lowest documented age was 9 years and the highest was 83 years with a medium of 43 years ±19.967.

Tumor size after its resection was obtained in about 88.10 % of cases (The lowest size of which was 6 mm, while the biggest was 200 mm, and the medium diameter was 35 mm ±19.935).

SDH gene mutation was reported in merely 68 patients as it wasn't routinely performed, whereas tumors of familial origin were seen in 81 patients.

Malignancy was detected in 67 patients (3.8 % of cases), whereas lymph node involvement was 44 lymph nodes. Moreover, 9 cases of pulmonary involvement, 2 cases in the brain, 1 case of vertebral involvement, 4 cases in the bones, 1 case in the mediastinum, 1 hepatic case, 2 systemic cases, 2 cases because of local invasion, and 1 tumor had malignancy that was documented only with histopathological analysis.

In terms of recurrence, CBT recurred in 30 cases (1.71 %) in the period of 1-to-7 years postresection.

4. Conclusion

CBTs are rare vascular anomalies, especially when they are a unilateral synchronous occurrence, and they possess the potential for malignant transformation. This neoplasia necessitates further analysis and documentation to establish innovative diagnostic guidelines, achieve optimal therapeutic interventions, and illustrate proper postoperative follow-up protocols. Misdiagnosis could delay treatment and result in devastating complications.

Abbreviations

PG

paraganglioma

CBT

Carotid Body Tumor

DUS

Doppler Ultrasound

CTA

computed tomography angiography

MRI

Magnetic Resonance Imaging

R-CCA

Right Common Carotid Artery

MSCT

Multi-Slice Computed Tomography

ICA

Internal Carotid Artery

ECA

External Carotid Artery

H&E

Hematoxylin and Eosin

IHC

Immunohistochemistry

CT

Computed Tomography

MRA

Magnetic Resonance Angiography

PET

Positron Emission Tomography

SDH

Succinate Dehydrogenase

EBRT

External Beam Radiation Therapy

Consent of patient

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Availability of data and materials

The datasets generated during and/or analyzed during the current study are not publicly available because the Data were obtained from the hospital computer-based in-house system. Data are available from the corresponding author upon reasonable request.

Ethics approval and consent to participate

Institutional review board approval is not required for deidentified single case reports or histories based on institutional policies.

Sources of funding

Not applicable.

Author contribution

OA: Conceptualization, resources, who wrote, original drafted, edited, visualized, validated, and literature reviewed the manuscript, and the corresponding author who submitted the paper for publication.

MS: 1st surgical assistant during the operation, manuscript writing and editing, validation, resources, literature review, and review of the manuscript.

EG: Visualization, resources, and review of the manuscript.

AM, MG: Vascular Surgery specialists who performed and supervised the operation, in addition to supervision, project administration, resources, and review of the manuscript.

All authors read and approved the final manuscript.

Guarantor

Omar Al Laham.

Research registration

Not applicable.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Declaration of competing interest

Not applicable.