Mantle cell lymphoma of the lacrimal drainage system: A rare case and review of literature

Abstract

Mantle cell lymphoma (MCL) of the lacrimal sac is an exceptionally rare tumor with only four such cases reported in literature, to the best of authors’ knowledge. The tumor is known to have extensive systemic and bone marrow involvement with poor prognosis and overall survival. The present case describes a 64-year-old male with primary MCL of the lacrimal drainage system, its diagnosis, and treatment options.

INTRODUCTION

Primary lacrimal drainage system (LDS) malignancies are rare among which the epithelial tumors contribute 44%–100% in different series.[1] Mesenchymal, lymphoproliferative, and melanotic tumors form a small subset of LDS malignancies. Among the lymphoproliferative tumors, diffuse large B-cell lymphoma is the most common, while mantle cell lymphomas (MCLs) are rare.[2]

MCL is a high-grade non-Hodgkin lymphoma and constitutes 1%–5% of the ocular adnexal lymphomas with a 5-year overall survival rate as low as 40%.[3,4,5,6,7] Primary MCL involving the LDS is extremely rare with only four cases reported in the literature, to the best of the authors’ knowledge.[3,8,9,10] The present case report describes a rare presentation of MCL primarily in the lacrimal sac and the nasolacrimal duct (NLD) with an orbital extension.

CASE REPORT

A 64-year-old male presented to the clinic with complaints of epiphora and mucoid discharge from the right eye of 1-year duration and a recent onset painless, progressively increasing swelling in the inferonasal aspect of the right eye of 3-month duration. The lesion was hard and nontender on palpation extending along the lateral aspect of the nose and above the medial canthal tendon [Figure 1a]. Irrigation revealed a clear regurgitation from the opposite punctum. The rest of the anterior and posterior segment examinations were within normal limits. Computed tomography scans of the orbits showed a right-sided heterogeneous irregular mass lesion in the lacrimal sac fossa extending into the NLD and the inferior meatus with dilation of the bony NLD. There was a bony destruction of the medial orbital wall with the extension of the mass lesion into the ethmoid sinus. The mass extended along the medial and inferior orbital walls to reach the midorbit [Figure 1b-d]. Nasal endoscopy showed a pinkish soft-tissue lesion at the NLD opening in the inferior meatus [Figure 1e]. A combined external and endoscopic approach for a surgical excision was planned similar to earlier published protocols.[11,12] The lesion was found to be well defined, capsulated, and separate from the orbital contents [Figure 1f and g]. Extension of the lesion into a dilated NLD was seen [Figure 1h]. The lesion was removed in 3 parts – the orbital component, the nasolacrimal component (external route), and the inferior meatal component endoscopically.

Figure 1.

Clinical picture showing a swelling in the right lacrimal sac area extending above the medial canthal tendon (a). Computed tomography scans orbit, axial and coronal cuts (soft tissue and bone windows) demonstrating an irregular mass of the lacrimal sac fossa with extension along the nasolacrimal duct (NLD) to the orbit, causing expansion of the bony NLD. There is infiltration of the mass into the medial orbit reaching up to the midorbit and into the ethmoid sinus medially (b-d). Endoscopic view showing the extension of the lesion into the inferior meatus through the NLD opening (e). Intraoperative images show the lesion entering the NLD (f) and the orbital component of the lesion (g). (h) Shows the expanded bony NLD with the lesion

Histopathological examination demonstrated the tumor tissue to be infiltrated with mononuclear round cells, arranged in sheets and lobes, having scanty cytoplasm, vesicular chromatin, and inconspicuous nucleolus [Figure 2a]. High-grade mitotic activity was present. The tumor cells showed a positive expression of CD20, BCL2, cyclin D1, and CD5, confirming the diagnosis of a MCL [Figure 2b-e]. Bone marrow infiltration was confirmed on histopathology [Figure 2f], and positron emission tomography (PET) scans showed involvement of the right cervical, bilateral axillary, mediastinal, right iliac, and inguinal nodes. Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP-R) chemotherapy was initiated and continued for 6 cycles and this helped resolve the lesion completely. PET scans posttherapy showed resolution of the residual lesion in the orbital adnexal region and the systemic lymph nodes. The patient is under close observation with the oncologist and is free of disease at present.

Figure 2.

Photomicrograph showing complete effacement of the soft tissue with infiltration of round cell tumor with basophilic nuclei and scanty cytoplasm (H and E, ×20) (a). Lesional cells showed diffuse expression of CD20, BCL2, and cyclin-D1 and scattered expression of CD5 (×20) (b-e). Bone marrow biopsy shows deposits of round cells indicating involvement by tumor cells (f)

DISCUSSION

MCL is a subtype of B-cell lymphoma with an aggressive clinical course. It arises from the B-cells of the inner mantle zone of the germinal center of the lymphoid follicle. The nuclei are irregularly cleaved, most having a chromosomal abnormality (t[11;14][q13, q32]), causing overexpression of cyclin D1 at the mRNA and protein levels.[13,14,15] Males are comparatively more predisposed to this subtype of lymphoma.[16] MCL is generally seen after the 5^th decade of life with a median age of 78 years.[16] The characteristic of MCL is the widespread systemic involvement (nodal and extranodal) with bone marrow being the most commonly involved site.[17] The dissemination throughout the body is commonly seen in MCL as most of these tumors originate from the pregerminal center of B-lymphocytes. These express chemokine receptors and specific adhesin molecules, which allow them to circulate to secondary lymphoid tissues.[3] Conjunctival involvement is also very common due to the expression of certain receptors and adhesin molecules.[3,9,10] Hence, early recognition and treatment are the key.

Literature review has revealed that so far only four cases of LDS, MCL has been reported earlier [Table 1].[3,8,9,10] Of the three cases where details are mentioned (including the present case), systemic and bone marrow involvement is seen, and the patients are doing well posttherapy. However, to comment on the overall survival, much longer follow-up of these patients is needed.

Table 1.

Mantle cell lymphoma of the lacrimal drainage system

	Age	Sex	Laterality	Symptoms	Systemic involvement	Bone marrow involvement	Treatment	Follow – up
Özen et al.[8]	65	Male	RE	Epiphora, swelling	Multiple lymphnodes + conjunctival MCL	Yes	Excision + by chemotherapy (R-CHOP)	Doing well postcompletion of therapy
Cruz et al.[10]	60	Male	BE	Routine screening, no symptoms	Conjunctival MCL	Yes	Incision biopsy + chemotherapy (R-CHOP + R-HIDAC)	5 years
Meng et al.[9]	56	Male	LE	Epiphora	Not mentioned	Not mentioned	Incision biopsy + chemotherapy (R-CHOP) + autologous stem cell transplant	38 months
Rasmussen[3]	-	-	Single case		-	-	-	No details mentioned specifically*
Present case	64	Male	RE	Swelling, epiphora and discharge	Multiple lymph nodes	Yes	Excision + chemotherapy (R-CHOP)	Doing well postcompletion of therapy

*describes series of MCL of the orbital adnexa in literature with no specific details of the case involving the lacrimal sac. RE: Right eye, LE: Left eye, BE: Both eyes, MCL: Mantle cell lymphoma, R-CHOP: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone, R-HIDAC: Rituximab + high-dose cytarabine

The prognosis of cases with MCL is calculated using the MCL International Prognostic Index which uses the following parameters – age, performance status, lactate dehydrogenase level, and white blood cell count, each multiplied by a constant. Ki-67 proliferation index and microRNAs can also be used to prognosticate a case with MCL.[3]

The treatment of MCL is chemotherapy with or without stem cell transplant. Chemotherapy drugs in treatment for MCL are CHOP. The addition of R-CHOP has improved the overall survival.[3] In combination with stem cell transplantation ± cytarabine therapy, the overall survival in patients <65 years of age has improved from 45% to 70%. Relapsed/refractory MCL has the worst prognosis; however, newer agents such as lenalidomide, bendamustine, temsirolismus (mTOR inhibitor), and bortezomib (proteosome inhibitor) may help improve the outcomes.[3]

In conclusion, MCL of the LDS mandates a thorough systemic evaluation along with bone marrow testing. Timely intervention with chemotherapy and stem cell transplantation where needed can improve the prognosis and the overall survival.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.