Radioguided Surgery of Non-palpable Neck Lymph Node in Lymphoma Patients

Abstract

Lymphomas have frequent relapses; early diagnosis is important to treat and improve outcomes. Clinical exam and imaging are useful but confirmation with biopsy is always required. Minimally exploratory surgery is a tool to take good samples with precision and safety. Evaluate the use of ROLL technique to track non-palpable lesions on the neck which were suspicious of recurrence in lymphoma patients. A retrospective review of the patients with high probability of lymphoma relapse who were biopsied using ROLL technique. Suspicious lesions on the neck where identified on the follow up of five lymphoma patients. Roll technique was used successfully to guide the biopsy. There were no complications. Relapse was confirmed in two patients; the other three was reactive follicular hyperplasia. Management was redirected on relapsing patients. ROLL technique proved to be a simple, safe and effective method to detect and biopsy non- palpable lesions on the neck of patients with suspicious relapsing lymphoma.

Introduction

Near 50% of non-Hodgkin’s lymphomas (NHL) and 30% of Hodgking’s lymphomas (HL) reappear after initial treatment [1]. The early detection of the relapse permits a prompt treatment. The best form to detect recurrences is still not clear. Some specialist relies on clinical symptoms and the diagnosis imaging, as computed tomography (CT) Scan, magnetic resonance imaging (MRI), ultrasound (US) and ¹⁸FDG PET-CT. The last one has been used as a marker of tumor viability and a guide during biopsy when suspicion of malignant lymphoma [2]. However, PET-CT could present false positive cases, especially after antineoplastic treatment, because it causes edema and changes in irrigation of tissue increasing radiotracer uptake [2]. That’s why biopsy is the most important diagnostic method in patients with suspected recurrent lymphoma. Material obtained by fine needle aspiration biopsy may not be sufficient due to the presence numerous reactive cells and few neoplastic cells in the lesion, which makes excisional biopsy the best option. Nevertheless, when ¹⁸FDG PET-CT detects diseased cervical lymph nodes in the initial recurrence, they are generally not palpable.

Many times, these lesions are localized in scarred and fibrotic tissues and will be hard to find intraoperatively. In these cases, radioguided occult lesion localization (ROLL) can be more precise, with smaller volumes of neck dissection and resection, less complications and morbidity for the patient [3].

This is a case series of post chemotherapy HL and NHL patients with positive neck findings by imaging, possible relapse. Non-palpable lesions were successfully biopsied using ROLL technique. This confirms the utility and advantages of radioguided technique to precisely find small non-palpable neck lesions with minimal dissection and complications on malignant lymphoma patients.

Materials and Methods

This is a retrospective review of the ROLL technique data base in our institution from December 2013 to June 2017. The search was focused on patients with HL and NHL whom after chemotherapy were studied with ¹⁸FDG PET-CT, CT scan or High frequency ultrasonography, with hypermetabolic adenopathy or findings with a high probability of recurrence (Fig. 1a, b). All patients had small non-palpable neck nodes, which were marked preoperatively with intratumoral injection of a radioisotope guided by high resolution ultrasound. Then intraoperatively the marked lesion was found using a hand-held gamma probe and was excised with a minimally exploratory surgery.

Fig. 1.

a Neck ultrasound shows a lymph node over IIA level side left, bigger size 6.6 mm. b¹⁸FDG PET-CT reveals small bilateral lymph nodes over IIA level (Deauville 4/5). In a case of 22-year-old female, who was treated for a non-Hodgking’s lymphoma T type, Anaplastic, ALK positive, with 6 CHOP cycles 7 years before

Technical Aspects

PET-CT studies were made in some of these patients, with a whole-body PET scan and a helical CT performed 60 min after the intravenous injection of 5 MBq/kg of body weight fluorodeoxyglucose (FDG) (Fig. 1b).

For histological confirmation, excisional biopsy was programed a few days later with Roll technique. All patients signed an informed consent for all the procedures. In 4th case a CT SCAN was done to know nodal status (Fig. 2a).

Fig. 2.

a CT scan demonstrates a lymph node on the right side, level IIA. b Imagen of SPECT after injection of 3 mCi of 99m-Tc-MAA, into a lymph node of level IIA right side. In a case of 32-year-old male with Hodgking’s lymphoma, nodular sclerosis. He was treated with ABVD, 6 cycles 1 year earlier

Patient´s lesion was marked in the center with ultrasound (13 MHZ transducer) guidance a day before surgery with 3 mCi of technetium-99m labeled macroaggregated albumin (99m-Tc-MAA), and the precise uptake of foci tumor was confirmed posteriorly with a Single photon emission computed tomography (SPECT) (Fig. 2b) or single photon emission computed tomography and computed tomography (SPECT/CT) (Fig. 3a–d). Then excisional biopsy was performed in all patients under general anesthesia, intraoperative lesion detection was achieved with a hand-held gamma probe (Europrobe 3^® navigator system), and it was selectively removed and sent for histological and immunohistochemical analysis. Absence of residual activity on the surgical site was finally confirmed.

Fig. 3.

The axial, sagittal and coronal single photon emission computed tomography computed tomography (SPECT/CT) after injection of 3 mCi of 99m-Tc-MAA, into a lymph node on right level IIA. In a case of an 80-year-old woman with a classic Hodgking’s lymphoma who was treated with 4 cycles of ABVD 1 year earlier

Results

Roll technique was used in five patients with lymphoma to guide the biopsy. Three females, two males, ages where between 22 and 80 years (Table 1).

Table 1.

Clinical characteristics of study patients

	Age	Sex	Initial diagnosis	Preoperative images	Final pathology
# 1	80	F	Mixed cellularity (HL)	PET/CT	Lymphoid follicular hyperplasia
# 2	22	F	Anaplastic lymphoma (NHL)	PET/CT	Lymphoid follicular hyperplasia
# 3	32	M	Nodular Sclerosing (HL)	PET/CT	Lymphoid follicular hyperplasia
# 4	61	F	Follicular lymphoma (NHL)	US + CT	Follicular Lymphoma
# 5	78	M	Myelodysplastic syndrome	CT	Peripheral T-Cell Lymphoma (NHL)

Diagnosis where 2 HL and 3 NHL with previous chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for HL and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) for NHL.

In their surveillance patients 1,2,3 had suspicious Hypermetabolic cervical lymph nodes on PET/CT (Deauville scores 4-5/5). These were non-palpable and patients were asymptomatic.

The 4th case had suspicious cervical lymph nodes on left levels III and IV. Fine needle biopsy was performed with inconclusive results (Few mature lymphocytes, hemorrhagic background) and the 5th patient had a suspicious mass on the pharynx, biopsies were no conclusive. Additionally, a non-palpable neck node less than 1 cm was found on a CT scan control.

All cases were programmed for excisional biopsy with roll technique, pre-incisional count was 3000 ± 200, intraoperative count was 15.000 ± 200 and residual bed count was 100 ± 10 (Table 2). Mean surgical time was 37.5 min and all patients were discharged the same day as there were no immediate or late complications.

Table 2.

ROLL technique characteristics

	Preop	Nodal size 1	Nodal size 2	Roll	Intraop counts	Residual counts
	LEVEL	Preop (mm)	Postop (mm)	99m-Tc-MAA
# 1	IIA	16 × 10	13 × 8	3 mCi	16.000	16
# 2	IIA	6.6 × 6.6	13 × 12	1 mCi	15.000	26
# 3	IIA	12 × 10	20 × 10	3 mCi	16.420	35
# 4	IV	14 × 10	20 × 15	2 mCi	7.100	5
# 5	III	< 10	10 × 10	2 mCi	7.900	20

The size of lymph nodes detected by preoperative imaging was approximately 6.6–14 mm in our study.

Histological, immune histochemical and flow cytometry studies were performed in all patient’s samples.

Patients 1, 2 and 3, who showed positive Hypermetabolic cervical lymph nodes on their PET-CT, finally resulted with reactive follicular hyperplasia. These patients where followed for 1 year with images that confirmed they had no relapse.

The fourth patient with positive findings on the CT scan and US, follicular Lymphoma, follicular growth pattern (CD23), High grade (3A) was confirmed with the excisional biopsy. This patient received 3 more cycles of chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone) and 18 sessions of radiotherapy.

The fifth patient, who had a suspicious 1 cm node, showed on his biopsy a Peripheral T Cell Lymphoma and continued his treatment with chemotherapy.

Discussion

This technique has proved to be precise and useful in non-palpable breast lesions [4] and on the neck with differentiated thyroid cancer [5].

In patients with Hodgkin lymphoma (HL) or aggressive non-Hodgkin lymphoma (NHL) after the third cycle of chemotherapy Interim 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography-CT (PET-CT) is used to detect early inadequate therapeutic response. This result is a good prognostic factor to predict progression free survival and is stronger than all the other pretreatment prognostic factors [6, 7].

In patients with lymphoma it is important to determine early after chemotherapy if the response is adequate, clinical signs and imaging are studied. PET-CT is frequently used because it enables the evaluation of the early metabolic changes that might indicate treatment refractivity or relapses needing more aggressive treatment strategies that may improve the likelihood and duration of remission [8, 9].

When positive, to improve outcomes these lesions must be biopsied promptly. Most of the time these lesions are located on the neck, where they are difficult to find intraoperatively because of their location, size, fibrotic tissue from previous surgeries or radiotherapy, adjacent multiple lymph nodes and dangerous structures.

Roll technique, where suspected lesions are preoperatively marked with a radioactive substance and detected in surgery with a gamma probe has many advantages over other frequently used techniques like wire-guided lesion localization. In non-palpable breast lesions, it allows lower volume of excised healthy tissue, decreased incidence of positive margins, decreased surgery time, better aesthetic outcomes and decreased possible complications [10].

On the neck, it is useful in patients with recurrent thyroid carcinoma on lateral and central regions, it contributes to surgical management proving higher success with less complication rates and lower morbidity [5, 11].

Further applications for this technique have been described, Infante et al. report 9 oncological patients with suspicious lesions found on PET-CT on different parts of the body (axillary, inguinal and supraclavicular region). In all cases they localized radiolabeled lymph nodes using ROLL technique [11].

In our cases the use of preoperative planar SPECT and an intraoperative hand-held gamma probe results in excellent node-detection rates. But, SPECT/CT allows the surgeon for better topographical orientation and delineation of lymph nodes against surrounding structures, for example, muscles, vessels, and bones. Additionally, the surgical time may be reduced thanks to better spatial resolution [12].

In this study, the aim was to evaluate the use of ROLL technique to track non palpable lesions on the neck, which were identified on PET-CT and were suspicious for recurrence in lymphoma patients.

We found this technique useful for excisional biopsies with diagnostic purposes in lymphoma patients, with non-palpable neck lymph nodes, ruling out the relapse in 3 patients but confirming it histologically in two other patients who adapted a new management.

Conclusion

In lymphoma patients, relapse is frequent and must be promptly diagnosed with imaging. When there are suspicious non-palpable lesions on the neck, the ROLL technique proved to be a simple, safe and effective method to detect and biopsy them with small incisions and minimal dissection, especially on previously intervened o irradiated necks.

Not all suspicious lesions found in PET-CT are malignant, but when histopathological confirmation of relapse is needed, radioguided surgery would be an effective technique.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interest.

Informed Consent

Informed consent was obtained from the patients for performance surgery.

Research Involving Human Participants and/or Animals

This article did not require any experiment involving any animal but was based on a retrospective clinical investigation just on human participants.