IPSO Practice Guidelines on Surgery for Lymphoma
Sharon Cox, Hafeez Abdelhafeez, Simone Abib
Disclaimer: The document, IPSO Practice Guidelines, and the information it contains are for authorized use by surgeons. IPSO cannot accept any liability and responsibility for any claims, loss or damage arising from the use of this document and its contents.
Version dated on 30 September 2020
Lymphomas are a heterogeneous group of malignancies of the reticuloendothelial system and are pathologically classified into two main groups – Hodgkin’s lymphoma (HL), and non-Hodgkin’s lymphoma (NHL).
Lymphoma accounts for about 10 to 12% of childhood malignancies, making it the third most common paediatric cancer, with NHL accounting for just less than half of the cases, and Burkitt’s Lymphoma predominating in this group.1
Historically, the role of the surgeon was to perform staging laparotomy for biopsy of nodes and the liver as well as a splenectomy. Cross sectional imaging has replaced this staging need, but an adequate tissue diagnosis is imperative to achieve an accurate diagnosis and classification using various histological techniques.2
The presentations, symptoms and signs of patients presenting with lymphoma are extremely variable. Patients can present with an obvious nodal or non-nodal mass and undergo a routine blood workup and biopsy or can present with various surgical diagnoses such as and abdominal mass, intussusception or appendicitis – where subsequent histology reveals the diagnosis. Other presentations include ongoing pain, abdominal distention and vomiting due to intestinal obstruction, obstructive uropathy, gastrointestinal bleeding or peritonitis from intestinal perforation.3, 4 Surgeons thus need to be aware of the potential diagnosis which may influence surgical management in this heterogenous group of patients.
- To provide adequate tissue sample for proper diagnosis (open biopsies/excision of accessible lymph nodes or mediastinal/abdominal masses)
- To treat surgical complications related to the disease (acute abdomen, for instance) or treatment
- To provide support:
- venous access for chemotherapy (please refer to the IPSO vascular access guideline)
- haemodialysis line insertion for tumour lysis syndrome
- evaluation of abdominal distension after initiation of treatment (intestinal perforation, neutropenic enterocolitis etc)
Preoperative: evaluation, images, special needs, biopsy need?
Patients may present to the surgeon in many different ways:
- Referral for biopsy
- Referral for an indwelling line for chemotherapy
- Referral for Haemodialysis line insertion for tumour lysis syndrome
- As an incidental finding in a patient presenting with another typical childhood surgical condition, especially during surgery for an acute abdomen
- As a complication after initiation of chemotherapy
As with any patient, a thorough clinical assessment in the form of history and physical examination is required.
Physical examination should include an assessment of the patient’s general condition, the location of any enlarged nodes, as well full assessment of the chest and abdomen, looking for masses or organomegaly. Other superficial areas include mandible swellings or patients presenting with suspicious mandibular masses and loose teeth. Uncharacteristic and uncommon skin lesions are also a rare form of lymphoma presentation.
Duration, characteristics and evolution of the mass, associated symptoms (fatigue, fever, night sweats, loss of weight, bruising and recurrent infections) may all be clues. In abdominal masses, associated pain, vomiting, constipation, GIT bleeding or urinary retention may suggest the nature of the disease process.
Full blood workup including blood counts, clotting profile, renal and liver functions as well as LDH need to be performed.
Imaging studies may include ultrasonography, CXR, or cross-sectional imaging in the form of CT Chest, and abdomen or MRI of the abdomen. Ultrasonography is the preferred initial investigation with the obvious advantages of lack of ionizing radiation, and provides information on the size, shape, and anatomy of the mass.
Mediastinal masses should have an initial chest x-ray with selected cases proceeding to CT scan for further information – with special emphasis on delineating the need for airway interventions during anaesthesia. If more than 50% of the tracheal lumen is compressed, needle or open biopsy should be performed under LOCAL anaesthesia only, as to avoid respiratory collapse. The use of steroids should be postponed until a biopsy is made, but in cases with severe impairment of the physiological status, with imminent risk of life, they should be considered, in agreement with the paediatric oncology staff.
Pre-operative consent is taken as per standard procedure, and in addition, surgeons should enquire whether further procedures such as line insertion, bone marrow biopsy, intrathecal chemotherapy or other relevant procedures should be included in the consent – this is particularly appropriate when frozen section is available – the results of which may inform decision and allow all of these procedures to happen in a single anaesthetic.
If the primary diagnostic work-up cannot identify the definitive cause of peripheral lymphadenopathy, a histopathological diagnosis is required. In general, children who present with a fast-growing tumor, or those who have a persistent lymphadenopathy despite being administered empirical antibiotics should be prepared to undergo a surgical biopsy. The possibility of malignancy usually drives surgeons to make this decision, and predictors include a fast-growing tumor, multiple levels of lymphadenopathy, supraclavicular location, hard or fixed nodes. Concomitant clinical symptoms such as persistent or unexplained fever, weight loss, organomegaly, abdominal pain associated with signs of intestinal obstruction (e.g., vomiting, abdominal distention, gastrointestinal bleeding), should be added to the aforementioned criteria for tumor biopsy.
An open biopsy to obtain adequate tissue samples for histopathological assessment is the preferred procedure. A significant lesion decided by clinical examination and preoperative imaging, should be removed in part (incisional) or in total (excisional) for a precise pathological result. Hodgkin lymphoma, non-Hodgkin lymphoma, neuroblastoma, leukaemia, rhabdomyosarcoma, and metastatic diseases are the most frequent neoplasia’s associated with cervical lymph node enlargement.
Definitive diagnosis of Lymphoma requires histological evaluation and sufficient tissue needs to be obtained for immunophenotyping, cytogenetics and molecular biology testing in order to arrive at an accurate diagnosis. Fine needle aspiration cytology (FNAC) is generally not sufficient as the tissue yield is too low for a full pathological diagnosis. Core, incision or excision biopsy is preferred. Fine needle aspiration cytology (FNAC) can provide a minimally invasive diagnostic aid. However, interpretation of FNAC require special cytopathology expertise. General anaesthesia is not needed for FNAC, therefore FNAC may be used as the first-choice approach for patients with large mediastinal mass who are at risk of perioperative respiratory collapse.
The most superficial and easily accessible mass should be approached first – with the intention of minimising surgical morbidity. Thus, if a patient presents with a thoracic lesion as well as nodes in the neck, biopsy of the neck nodes would provide the least surgical morbidity.
The use of frozen section at the time of biopsy has the advantages of allowing sufficient histological assessment to make further decisions relating to line insertion, lumber puncture or bone marrow biopsy all in the same anaesthetic, thus streamlining management.3
For deeper lesions, the use of core needle biopsy under radiological guidance is also an option – and in this instance surgical morbidity is avoided.3
Special considerations for lymph node sampling
Preoperative evaluation of mediastinum enlargement should be performed before a child is given general anesthesia, due to the risk of ventilation problems and death during induction, when there is a significant mediastinal mass compressing the airway. In this situation, the surgeon should look for peripheral lymph nodes that can be biopsied under local anesthesia or cavity fluid that can be obtained via thoracentesis or paracentesis to make a diagnosis.
Contraindications for general anesthesia in patients with anterior mediastinal mass include more than 50% reduction of the predicted expiratory flow rate or more than 50% reduction of the predicted tracheal diameter. Orthopnea is the most ominous predictor of respiratory collapse at the time of general anesthesia.4
If general anesthesia is needed, the anesthesiologist should be aware of the risks and adjust the sedation or anaesthesia accordingly. This may be by positional changes, performing the biopsy in a seated or lateral position, or with specific intubation techniques appropriate to the patient.
- Sometimes, more than one biopsy may be needed to diagnose lymphoma. To avoid that situation, the surgeon should ensure that a representative size of tissue specimen is obtained. If the diagnosis is “lymph node reactive” or “inconclusive” on open biopsy, the patient should be followed up with further investigation until the case is resolved.
- It is important to note that patients from countries where TB and HIV are prevalent may have concurrent different diagnoses.
Special considerations for abdominal Burkitt lymphoma
Image guided procedures should be avoided when treating a child with suspected abdominal Burkitt lymphoma, due to the risk of intestinal perforation. In such cases, it is safer to perform an open biopsy by laparotomy or laparoscopy.
Endemic Burkitt lymphoma most commonly involves the jaw, however abdomen primary is very common in both endemic and sporadic types. In the abdomen, the disease can preferably involve mesenteric lymph nodes (more common in high income countries) and/or preferably involve intestinal wall in various segments (frequent presentation in LMIC). Patients with abdominal primary may present initially to surgeons, either with an asymptomatic abdominal mass or acute abdomen.
Intussusception is a well-known paediatric entity occurring in the majority of cases in patients under 2 years of age, and is usually idiopathic in nature. A lead point is found in less than 10% of cases, and these usually occur in older children and in patients over 4 there needs to be a high index of suspicion that a lead point exists. While most lead points are benign, lymphoma of the bowel may well precipitate intussusception, with Burkitt’s lymphoma/ mature B-cell non Hodgkins Lymphoma being the most common associated subtype, and post-transplant lymphoproliferative disease being an infrequent finding. In most instances’ patients presenting with a lead point will progress to surgery either as a lead point was confirmed on ultrasound, the intussusception is not in the typical ileo-colic site, due to recurrence after reduction, or due to irreducibility on reduction enema attempts. Either way, the principles remain the same as for biopsy.
Approximately just less than one third present with lower abdominal pain mimicking acute appendicitis. Therefore, patients may be explored in the acute setting and more commonly found to have a locally extensive disease involving the mesentery, retroperitoneal and intraperitoneal space.
The abdomen is the most frequent site of involvement in nonendemic Burkitt’s lymphoma.6 For abdominal masses the approach can be via open surgical techniques or laparoscopy, depending on both the clinical situation as well as the facilities and expertise available. In all cases it is important to remember that the goal is to safely sample representative lesions. Excision of complex masses is not indicated and destructive surgery should be avoided.3, 6 If at all possible, biopsy of nodal masses or involved solid organs is preferred to biopsy of the bowel, where fistulation is a potential complication.
If the child presents with acute abdomen, the surgeon’s role is that of stabilization of the abdominal condition.
If an unsuspected malignancy resulting in bowel obstruction or perforation is found, extensive resections and anastomosis should be avoided. Rather, a stoma to divert and control bowel contents and a biopsy of the lesion is appropriate – especially under emergent conditions. This can temporize the patient until referral to an appropriate centre and /or formal diagnosis is achieved.
The role of surgery should be diagnostic only and conduct of surgery should be as least invasive as possible to facilitate rapid recovery and starting of chemotherapy postoperatively. If obstruction and/or perforation are present, leading to the need of intestinal resection, stomas are safer until chemotherapy can be administered, for the tumor has rapid growth and involves the intestinal wall. If an anastomosis is performed, there is a high risk of anastomotic leak, that leads to sepsis and death. Thus stomas are safer in an acute setting. Less commonly the disease is limited to a short segment of bowel and mesentery, complete surgical resection of limited disease with end to end anastomosis is desirable because this result in de-escalation of therapy and excellent outcome. If that occurs, the surgeon must keep in close communication with the oncologist, in order to delay the initial chemotherapy, to avoid anastomotic leak.
Sometimes, perforation can occur after beginning of chemotherapy, for the intestinal wall melts with the tumor. In such cases, since the child will be neutropenic and with low platelet count, stomas should be indicated, instead of primary anastomosis.
Post chemotherapy abdominal disease is infrequent due to the efficacy of medication and thus the role of second look procedures is limited.6
An infrequent complication after chemotherapy induces mucositis may be that of a bowel stricture.9 Should this occur, resection and anastomosis is appropriate.
- Primary gastric Burkitt lymphoma is very rare in childhood. Many gastric lymphomas including mucosa-associated lymphoid tissue lymphoma are associated with Helicobacter pylori infection or acute bleeding.8 These patients would undergo endoscopic assessment and biopsy as per normal protocols.
- PTLD (post-transplant lymphoproliferative disorder): surgery may be needed to treat intestinal obstruction or severe GI bleeding related to this situation.
- Lymphomas can present infiltrating ovaries and testis. In such cases, gonadectomies should not be made, only biopsy for diagnostic confirmation. Renal infiltration can also occur. Image studies usually show bilateral involvement in gonadal and renal lymphomas.
Surgery is of essence in providing adequate vascular access for chemotherapy and for dialysis, if needed.
In biopsy procedures, post operative period is usually uneventful.
In cases where intestinal resections with stomas were made, since usually an ileostomy is needed, care should be taken in order to prevent metabolic support and adequate fluid and electrolyte replacement. Nutritional support is of essence. The skin near the ileostomy should be early protected to avoid severe dermatitis.
Should the disease be localized and a primary anastomosis performed, close communication with the oncologist should be made, to postpone the initiation of chemotherapy.
Infectious complications may be slightly higher in a population with bone marrow involvement as well as those on chemotherapy. Preoperative prophylactic antibiotics need to be given for surgical interventions to avoid these.
In case a stoma is made, care should be taken to prevent and treat metabolic, nutritional and fluid loss.
Dermatitis around the stoma is common. Early local and intensive care should be made.
Be careful not to perforate the bowel while sampling the tumor for diagnosis.
This is a haematological disease that is treated by chemo. Surgery is important for diagnosis and to treat complications. Avoid destructive surgery – chemotherapy is the mainstay of treatment in lymphoma.
Protect the skin as soon as the stoma is made in order to prevent severe dermatitis.
Sometimes more than one biopsy may be needed to diagnose lymphoma. To avoid that, be sure to biopsy a representative lymph node. It is important to remember that in countries where TB and HIV are prevalent, there could be concurrent different diagnoses.
Intestinal perforation can occur after the initiation of chemotherapy.
Intestinal perforation can occur while making a biopsy.
Should an intestinal resection be needed, avoid primary anastomosis, stomas are safer. In rare cases in which the disease is localized, resection and primary anastomosis can be made, but close communication with the oncologist in order to postpone chemotherapy is advised.
If there is gonadal involvement, refrain from doing gonadectomies, only biopsies are needed.
- Foley RW, Aworanti OM, Gorman L, McGovern B, O’Sullivan M, Smith OP, et al. Unusual childhood presentations of abdominal non-Hodgkin’s lymphoma. Pediatr Int. 2016;58(4):304-7.
- Morris-Stiff G, Cheang P, Key S, Verghese A, Havard TJ. Does the surgeon still have a role to play in the diagnosis and management of lymphomas? World J Surg Oncol. 2008;6:13.
- Vural S, Baskin D, Dogan O, Polat N, Caliskan C, Urganci N, et al. Diagnosis in childhood abdominal Burkitt’s lymphoma. Ann Surg Oncol. 2010;17(9):2476-9.
- Perger L, Lee E, Shamberger R. Management of children and adolescents with a critical airway due to compression by an anterior mediastinal mass. J Pediatr Surg. 2008 Nov;43(11):1990-7.
- Faizan M, Anwar S, Khan S. Demographics and Outome in Paediatric Non-Hodgkin Lymphoma: Single Centre Experience at The Children Hospital Lahore, Pakistan. Journal of the College of Physicians and Surgeons–Pakistan : JCPSP. 2018;28(1):48-51.
- Shamberger RC, Weinstein HJ. The role of surgery in abdominal Burkitt’s lymphoma. J Pediatr Surg. 1992;27(2):236-40.
- Bussell HR, Kroiss S, Tharakan SJ, Meuli M, Moehrlen U. Intussusception in children: lessons learned from intestinal lymphoma as a rare lead-point. Pediatr Surg Int. 2019;35(8):879-85.
- Kim SC, Hwang JW, Lee MK, Hwang PH. Rare Case of Primary Gastric Burkitt Lymphoma in a Child. Korean J Gastroenterol. 2016;68(2):87-92.
- Gupta G, Agarwala S, Thulkar S, Shukla B, Bakhshi S. Jejunal stricture: a rare complication of chemotherapy in pediatric gastrointestinal B-cell non-Hodgkin lymphoma. Journal of pediatric hematology/oncology. 2011;33(2):e69-71.