Non-Hodgkin lymphomas (NHL) are a wide range of tumors that originate in the lymphoid tissue. The malignant proliferation of lymphocytes in the lymphatic system could result in developing a neoplasm in the lymph nodes, bone marrow, spleen, liver or the gastro-intestinal tract. Non-Hodgkin lymphomas are more common than Hodgkin lymphomas. The majority of NHL derive from B-cells (85%), the other having T-cell progenitors or NK (natural killer) progenitor cells. Types of NHL include chronic lymphocytic leukemia, cutaneous B-cell lymphoma, cutaneous T-cell lymphoma, follicular lymphoma and many other neoplasms originating in B-cells or T-cells depending on the affected organ, the subtype of cells and the benignant or malignant evolution.^1-3

The most common clinical signs include peripheral asymptomatic lymphadenopathy, B symptoms (fever >38 degrees Celsius, night sweats, weight loss, that is greater than 10% in the past six months) and persistent fatigue. In low grade lymphomas, the peripheral adenopathy is painless, slowly progressive and can resolve spontaneously, while in the intermediate and high-grade lymphomas, adenopathy may occur in the mediastinal and retroperitoneal areas. Splenomegaly and hepatomegaly are common findings in the high stage lymphomas. Bone marrow involvement accompanied by cytopenia can be present. Anemia is reported in 33% of the patients, who are diagnosed during an initial stage. Cutaneous infiltration can occur in adult T-cell leukemia and anaplastic big cell lymphoma. Other symptoms depend on the following aspects: the site of the tumor, its spread, the stage of invasion and may be subject to differential diagnosis with other tumoral masses.^1-4

Diagnosis is based on clinical observations, laboratory testing, imagistic findings, biopsies or lumbar punctures. The laboratory tests should include a complete blood count, biochemistry testing (including LDH – lactate dehydrogenase, calcium levels, liver function tests), beta-two-microglobulin, HIV (human immunodeficiency virus) serology, HTLV-1 serology (human T-cell lymphotropic virus 1), hepatitis B testing. Imagistic tests that are useful, are the thoracic radiography, the CT (computed tomography) scan, the PET (positron emission tomography) scan if radiography confirms the presence of adenopathy. Other paraclinical tests, which can be performed to set an accurate diagnosis, may include MUGA (multigated acquisition scan), brain MRI (magnetic resonance imaging) or spinal cord MRI. Patients undergo lymph node biopsy to confirm the diagnosis. Histopathological findings include architectural destruction, capsular and adipose tissue invasion of the neoplastic specific cells. Lumbar puncture can also be needed in particular forms of lymphomas.^1,3

Treatment of NHL includes various methods such as chemotherapy, radiation therapy, bone marrow transplant, blood transfusions or surgery. Chemotherapy is the most common one and implies using combined substances such as rituximab + cyclophosphamide, doxorubicin, vincristine, prednisone. Aside for cytotoxic agents, monoclonal antibodies, proteasome inhibitors, immunomodulators and corticosteroids may be of great use. Surgical treatment is needed if local invasion and spreading is present, no matter the disease stage, in order to reduce the patient’s discomfort.^1-3

Case report

A 38-year-old male patient was admitted in our hospital from 13.11.2017 until 15.11.2017 to undergo surgery for the removal of a tumoral mass, in the upper eyelid of the right eye, which we suspected to be a recurrence of a former diagnosed and surgically removed NHL. The patient resided in the urban area.

We had the patient tell us the history of the tumoral onset, which gave us a wide and detailed background of his tumoral recurrence and treatment. From his statements we point out that he was diagnosed with non-Hodgkin lymphoma in 2005 at another hospital unit. He underwent a long series of non-surgical treatments including radiation therapy (2007), chemotherapy (2008), again radiation therapy (2009), interferon treatment (2010), and for the last time radiation therapy (2012), all of them performed at the same hospital (hospital one – H1) where the NHL had been diagnosed.

The patient stated that he developed bilateral growth in the inguinal region (tumor one – T1) in 2011, for which he underwent surgery (surgery one – S1) for removal during the same year and at the same hospital where he was under observation and treatment. The operation was performed by a general surgeon, under spinal block. The patient has had no local recurrence at this level ever since. In 2014 a tumoral mass developed in his posterior right arm (T2), for which he was advised to undergo surgical removal. In 2014 he was operated (S2) and the neoplasm was removed in another hospital (H2), by a general surgeon. In 2015 he underwent the third surgery (S3), because the right arm lymphoma recurred. Again, the surgery was performed by a general surgeon, in a different medical unit (H3). Local recurrence was not reported since then.

From the summer of 2014, another tumoral mass appeared in his upper eyelid (T3). He started a series of another three surgeries, performed at the fourth different hospital (H4), this time by a plastic surgeon. The operations were necessary because local recurrence occurred twice, after the first removal in the summer of 2014 (S4). Chronologically the next surgery was performed in the winter of 2015 (S5, H4), shortly after the second removal of the posterior right-arm mass (T2, S2, H3). The sixth, and final surgery, happened in the spring of 2017 (S6, H4), also for an upper right eyelid lymphoma, which had its third recurrence afterwards, for which he addressed to our hospital and our surgical team.

The patient was admitted to our unit and we requested a full blood count, biochemistry tests, glucose, coagulation, urea and creatinine, and hepatic enzyme tests. No abnormalities were found in any of the tested fields. During the clinical exam, we observed the bilateral inguinal scars and the posterior right arm scars. We also noticed some pathological change in the appearance of the skin in the right zygomatic and temporal areas: numerous superficial telangiectasias (Figure 1).

Figure 1. Numerous superficial telangiectasias in the right temporal and zygomatic region and lateral view of the tumoral mass of the superior-lateral aspect of the right eye’s upper lid

The subcutaneous tumoral mass was situated at the level of the right eye’s upper lid, laterally and superiorly, near the orbital-frontal junction, having an appearance similar to any small lump (Figure 2). It was round in shape, had approximately two cm in diameter, was easy to mobilize on the underlying structures, had an elastic consistency and was not accompanied by any inflammatory signs or adenopathy. The above described mass was not painful, but it bothered the patient while trying to open the eyelid, also limiting his visual field. We want to underline that this was his fourth surgery in the attempt to remove this growth, a recurrence of previous masses.

Figure 2. Anterior view of the superior-lateral aspect of the right eye’s upper lid, notice how the tumoral masses push the skin forward

The goal of our surgical procedure was to remove the entire tumoral structure, without damaging any nervous or muscular components, thus preserving both function and aesthetic aspects. When performing the incision, we had to ensure that our visual intra-operatory field was big enough, still trying to balance the scaring process and the aesthetic outcome. The patient was put under general anesthesia, and was given one dose of amoxicillin 875 mg/ clavulanic acid 125 mg for prophylactic reasons. The incision was made onto the center of the tumoral mass, in a horizontal wavy shape (Figure 3).

Figure 3. Incision site, notice the W shaped, horizontal placement of the line, right above the tumoral mas

Dissection through the anatomical layers was performed, and the orbicularis oculi muscle’s orbital part was exposed. At this level, we found two round-shaped tumoral masses, connected through muscle fibers, very poorly delimitated from the surrounding muscle structures. It was a laborious and thorough operation that we had to perform, in order to excise the pathological structures, without further damaging the muscle, using surgical loupes with 3.5x magnification. We succeeded to extract both masses (I – 2/1/0.5 cm and II – 2/0.8/0.2 cm) from a macroscopic point of view. We did thorough hemostasis and sutured the split muscle fibers to restore the orbicularis using absorbable monofilament thread. In the end, simple sutures were applied to close the skin. We put an eye-patch bandage and advised our patient not to open the eye for 24 hours, in order to avoid bleeding and splitting of the muscle sutures due to muscle movements. We sent the two excised masses to histopathological examination. On the first day after surgery the patient was feeling very well. We observed that no motor or sensitive nerve branches were damaged, the lid was perfectly functional and the patient was very satisfied with the outcome. Minimal edema was present. We discharged the patient the second day after the procedure and we had him come back for dressing changes two times during the next week. After seven days we removed the sutures and the surgical wound looked well. We recommended that the patient come back for periodical check-ups at one month, three months, six months and 12 months post-surgery. He was instructed to continue the oncology follow-up with his physician immediately after discharge.

The pathology report confirmed the nature of the fragments. The two masses were made of connective, vascular and muscle tissue with numerous nodular lymphoid infiltrations. The lymphoid infiltrations were composed of small sized, monomorphic lymphocytes, combined with histiocytes.

Many important motor and sensorial functional anatomical structures are situated or pass through the area where the abnormal growth was located. Our primary objective was to eliminate the lump, but any incision or dissection had to be carefully calculated as to minimize the local damage. The orbicularis oculi muscle is situated superficially, underneath it lays the orbital septum. Its vascular supply is provided by branches of the superficial temporal and facial arteries and also from the ophthalmic artery, while innervation is given by the temporal and zygomatic branches of the facial nerve (the seventh nerve). The superior lateral palpebral artery and branches of the superior ophthalmic vein and vorticose veins reside in the deeper layers. The innervation of the deeper structures is offered by branches of the supraorbital nerve, anterior ethmoidal nerve, and lacrimal nerve. In the deeper layers, the lateral fixation of the levator aponeurosis and the lacrimal gland complete the anatomy of the lateral superior orbital region.^5-7

The two masses were very adherent to the nearby orbicularis oculi muscle, thus splitting parts of the muscle fibers was necessary to dissect the whole mass. The limits of the tumors were unclear, given their color which was similar to the muscle, their shape, and their structure. The main function of the orbicularis is to close the eyelids, and assist the pumping of tears into the nasolacrimal duct system, therefore any malfunction of the muscle results in not closing the eye-lid properly and in pathological alteration in the clearance of the tears from the eye.⁷

On the first day after surgery, we asked our patient to slowly open and close the eyelid so that we could evaluate that the normal function had been preserved. He responded well, and his function and local sensorial perception were perfectly preserved. Edema and bleeding were minimal. We discharged him on the next day, with only a minimal sterile strip dressing. We have to point out the importance of the one-night rest with the eye patch, which did not allow the patient to open the eyelid, thus giving the muscle a short time to recover.

The anatomy of the eyelid is very complicated, and the damage of the main structures is very hard to undo. Thus, we used very delicate, minute surgical instruments for dissection, a needle-shaped cauterization tip and surgical loupes. The surgeon’s position and posture at the operating table have to be very stable, in order to minimize the physiological tremor of the hands. Although the experience of the surgeon is very wide, this case is unique, given the origin, the recurrence and the localization of the mass. Thus, a thorough anatomy and physiology review was needed before surgery, to ensure the maximum and optimal outcome for the good of the patient.

This very complex case should address a large medical team, including hematologists, oncologists, plastic surgeons, pathologists, psychologists and radiologists. Although we are tempted to solve the problem as soon as we can, the patient undergoes significant mental stress, thus exposing him to depression. A good communication between doctor and patient must be established, so that the patient fully understands and acknowledges the procedure he will undergo, its potential complications and the high possibility of recurrence.

We presented a very rare case, about a NHL located on the superior-lateral area of the right eye’s upper lid. We had to establish a thorough disease history of the patient, and to overlook all of his past surgical data before we operated the tumoral mass. Only a few lymphomas are selected by oncologists to be surgically removed, and this is usually the case of the tumors that are non-responsive to the standard treatment.

We removed two neoplasms located intramuscularly in the orbicularis oculi muscle. This muscle has a very important function in opening and closing the eyelid. Although the dissection was performed extremely carefully, it was impossible to spare the muscle fibers, which surrounded the masses. We repaired the muscle, and advised the patient to keep the eye closed for 24 hours. The outcome was very good, and the motor function of the orbicularis oculi was preserved fully. The patient was very satisfied with the result. Although it was his fourth surgery at the same level, but the first operation by our surgical team, our patient stayed positive and didn’t report any recent local recurrence or complaints until today. The patient came back for the one month and three months follow-up, and we were very pleased with the result, the scaring being minimal.

We did a lot of research but we noticed that the medical literature has very few stated cases similar to ours. This particular one is a challenge even for experienced surgeons because of the nature of the tumoral mass, which is not easy to dissect or to be identified as a different structure from the surrounding tissue. The edges of the abnormal masses are particularly difficult to excise, because the surgeon has no macroscopic control of the tumoral limits. From our experience with this case, we learned that the non-Hodgkin lymphoma is a very difficult to treat tumoral mass, thus it requires a lot of surgical experience and knowledge.

1. Vinjamaram S. Non-Hodgkin Lymphoma. 2017. Accessed on: 01.02.2018. Available at: https://emedicine.medscape.com/article/203399-overview

2. Mayo Clinic Staff. Non-Hodgkin’s Lymphoma. 2018. Accessed on: 01.02.2018. Available at: https://www.mayoclinic.org/diseases-conditions/non-hodgkins-lymphoma/symptoms-causes/syc-20375680

3. Beers MH, Porter RS. Manualul Merck de diagnostic și tratament, ediția a XVIII-a, Bucharest: ALL.

4. Freedman AS, Friedberg JW, Aster JC. Clinical presentation and diagnosis of non-Hodgkin lymphoma. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc; 2017.

5. Netter FH. Atlas of Human Anatomy, 4th Edition, Philadelphia, USA: Saunders Elsevier; 2006.

6. Rohen J, Yokochi C, Lutjen-Drecoll E. Color atlas of anatomy, a photographic study of the human body, 6th Edition, Baltimore & Philadelphia, USA, and Stuttgart, Germany: Lippincott Williams & Wilkins, and Schattauer GmbH; 2006.

7. Tong J, Bhimji SS. Anatomy, head, face, muscles, orbicularis oculi. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018.