Optometry - Journal of the American Optometric Association
Volume 81, Issue 5 , Pages 234-239, May 2010

Conjunctival plasmacytoma

  • Jasmine W. Yumori, O.D.

      Affiliations

    • West Los Angeles Veterans Affairs Health Center, Los Angeles, California
    • Western University of Health Sciences, Pomona, California
    • Corresponding Author InformationCorresponding author: Jasmine W. Yumori, O.D., 309 East Second Street, Pomona, California 91766
    • ,
  • Pauline Ilsen, O.D.

      Affiliations

    • West Los Angeles Veterans Affairs Health Center, Los Angeles, California
    • Southern California College of Optometry, Fullerton, California
    • ,
  • David C. Bright, O.D.

      Affiliations

    • West Los Angeles Veterans Affairs Health Center, Los Angeles, California
    • Southern California College of Optometry, Fullerton, California

Article Outline

Abstract 

Background

Plasmacytomas are plasma cell tumors that may be a primary or secondary tumor focus, the latter of which are associated with multiple myeloma. We present a rare case of a solitary extramedullary plasmacytoma involving the conjunctiva.

Case Report

A 33-year-old white man presented with the initial complaint of redness in both eyes, more in his right than left eye. A vascularized conjunctival lesion was noted in his right eye. The patient underwent excisional biopsy, which found a conjunctival plasmacytoma.

Conclusion

Although plasmacytomas of the eye and orbit are rare, it is important to be familiar with these tumors that may be associated with multiple myeloma. Definitive diagnosis is made by biopsy and histopathologic examination of the tissue. Plasmacytomas may be treated with external beam radiation, local excision, or radiotherapy after surgical excision. Long-term follow-up, including periodic systemic evaluation, is required to establish that orbital involvement is not an early manifestation of multiple myeloma.

Keywords: Plasmacytoma, Solitary extramedullary plasmacytoma, Multiple myeloma, Conjunctival tumor, Excisional biopsy

 

Plasmacytomas were first described by Dalrymple and Bence Jones in 1846.1 Plasmacytomas are collections of plasma cells that have become modified to produce large amounts of immunoglobulin and are classified as a type of B-cell non-Hodgkin lymphoma.2 Although the etiology of plasmacytoma is still unknown, a link to a hepatitis C viral infection has been suggested3; high hepatitis C virus sero-prevalence has been detected in patients affected by B-cell non-Hodgkin's lymphoma,4 and active hepatitis C virus, including replication, has been identified in the bone marrow of patients with multiple myeloma.5

Plasmacytomas may be a primary or secondary tumor focus, the distinction of which is based on the presence of systemic disease. The most malignant plasma cell neoplasm is multiple myeloma, which may manifest as a secondary plasmacytoma and is aggressive, metastatic, and represents 1% of all cancers6 and 10% of the hematologic malignancies.7 Plasmacytomas typically affect patients between the ages of 50 to 80 years.3 Systemic complications, such as localized bone symptoms, alterations in blood calcium levels, and kidney damage, may be present not only in multiple myeloma but also in patients with a solitary plasmacytoma.3 Specifically, patients may report bone pain caused by bone lysis and/or bone fracture from altered osteoclast/osteoblast activity leading to calcium mobilization from affected bone; elevated calcium levels lead to tubular damage and subsequent kidney damage.3

Primary plasmacytomas may be divided into medullary, referring to bone lesions, or extramedullary, referring to soft tissue lesions.6 Known as solitary extramedullary plasmacytomas (SEMP), primary lesions represent 3% of plasma cell neoplasms,8 are locally invasive, and do not metastasize often. Extramedullary plasmacytomas occur between the fourth and seventh decades of life, with the majority of cases involving the upper respiratory tract9 but may rarely manifest in and around the eye. Extramedullary plasmacytomas may precede multiple myeloma.8

In a series reviewing conjunctival tumors, 128 lymphoid tumors of the conjunctiva were identified, representing the fifth most common conjunctival tumor, and accounting for 8% of all conjunctival tumors.10 Plasmacytomas accounted for 1% of the lymphoid tumors; other lymphoid tumors included were malignant lymphoma (77%) and benign reactive lymphoid hyperplasia (22%).10 Lymphoid tumors of the conjunctiva were most commonly found in the fornix (37%), followed by the extralimbal bulbar conjunctiva (33%), and lastly the limbus (8%); lymphoid tumors were most likely located diffusely (34%), followed by superiorly (24%), inferiorly (20%), nasally (17%), and temporally (5%).10 The mean age of detection for malignant lymphoid, along with epithelial, lipomatous, secondary, and leukemic tumors, was 60 years, and most patients in the survey were classified as white (89%); 37% of lymphoid tumors presented bilaterally in this series.10 In a series focusing on conjunctival lymphoid tumors at the same institution, systemic lymphoma was detected in 47% of the 117 patients with bilateral disease and 17% with unilateral disease.11 We report on a case of a conjunctival solitary extramedullary plasmacytoma.

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Case report 

A 33-year-old white man presented with a chief concern of constant redness in both eyes, more in his right than left eye. The patient's ocular and medical histories were negative, and he denied any taking medications or having allergies. His family ocular history was positive for glaucoma in his paternal grandfather. External evaluation found the pupils were equally round and reactive to light without any afferent pupillary defect, extraocular motilities were unrestricted in all gazes, and confrontation visual fields were full to finger counting in both eyes.

His uncorrected visual acuities were 20/20− in each eye, with a manifest refraction of +0.50 in both eyes yielding a best-corrected visual acuity of 20/20 in each eye. Intraocular pressures (IOPs) were 20 mmHg in each eye predilation and 23 mmHg in each eye postdilation with Goldmann applanation tonometry (GAT). Anterior-segment evaluation with slit lamp examination found clogged meibomian glands and inflamed nasal pterygia (1.8 mm across the limbus in his right eye and 2.4 mm in his left eye). A mildly elevated, mobile, faint pink, vascularized, 4.5-mm by 4.5-mm lobular temporal bulbar conjunctival lesion in his right eye was also noted. His dilated fundus examination findings were unremarkable in both eyes with a cup-to-disc ratio of 0.40 with healthy rims in both eyes.

The patient had inflamed pterygia and meibomitis diagnosed in both eyes and a suspicious bulbar conjunctival lesion diagnosed in his right eye. He was started on ketorolac tromethamine 0.5% ophthalmic solution 4 times a day in both eyes for 7 days, lid hygiene was initiated, and he was asked to return to clinic in 3 months for monitoring. Based on his postdilated IOP spike, he was also considered a glaucoma suspect, and an IOP check and baseline threshold visual field examination was planned at his follow-up visit.

The patient failed to return at the recommended follow-up time and instead returned to the clinic a year and a half later reporting continuing redness in both eyes for the prior 2.5 years; he requested eye drops to decrease redness. He reported that the ketorolac tromethamine 0.5% ophthalmic solution previously prescribed did not help, and occasional use of naphazoline hydrochloride 0.025% and pheniramine maleate 0.3% ophthalmic solution helped only temporarily. He also commented that the vascular lesion in his right eye had been stable for the prior 1 to 2 years. Slit lamp biomicroscopy found a mild follicular reaction in the inferior palpebral conjunctiva of both eyes, stable nasal pterygia in both eyes, and the suspicious bulbar conjunctival lesion in his right eye. IOPs were 16 mmHg in both eyes with GAT. He deferred dilation. Olopatadine hydrochloride 0.1% ophthalmic solution and artificial tears (polyvinyl alcohol 1.4% ophthalmic solution) were started twice a day and 4 times a day, respectively, in both eyes for follicular conjunctivitis, warm compresses and lid hygiene were re-advised for meibomitis, and a consult to ophthalmology (within 2 weeks) was arranged for further evaluation of the conjunctival lesion in his right eye. An IOP check, baseline visual field determination, baseline stereo disc photos, and dilation were also deferred to the follow-up examination.

Two weeks later at our cornea/anterior segment clinic, the findings were similar to those of prior examinations, and IOPs were 20 mmHg in both eyes with GAT. The dilated fundus examination was unremarkable, and a trial of prednisolone acetate 1% ophthalmic suspension every 2 hours in the right eye with a slow taper was initiated to rule out an inflammatory process in the conjunctival lesion. Follow-up was scheduled in 3 weeks for consideration of excisional biopsy, but the patient failed to return as instructed and was lost to follow-up.

Three years later, the patient returned for evaluation of the conjunctival lesion. He reported growth of the conjunctival lesion since his prior examinations with increased redness and foreign body sensation in both eyes. He denied using any medications, including eye drops, and his presenting visual acuities remained 20/20 in each eye. Anterior segment evaluation with a slit lamp found a papillary reaction in both eyes and nasal pterygia extending now 2.0 mm across the limbus in his right eye and 2.7 mm in his left eye. The elevated conjunctival lesion previously noted in the right eye was now noted to be 4.6 mm by 5.8 mm, and 2 larger “feeder” vessels in the temporal bulbar conjunctival lesion in his right eye were also noted. Baseline anterior segment (see Figure 1) and optic nerve head photos were taken in both eyes with patient consent. An excisional biopsy of the conjunctival lesion in the right eye was planned with subsequent excisional biopsy of the pterygia also considered.

  • View full-size image.
  • Figure 1 

    A, B, Anterior-segment photographs of the right eye show plasmacytoma on the temporal bulbar conjunctiva in the right eye and a pterygium nasally. C, D, Anterior segment photographs of the left eye show a pterygium nasally.

An excisional biopsy of the conjunctival lesion was performed, and histopathologic examination found a plasmacytoma, specifically monoclonal kappa. Immunochemistry with cd138 and k/l light chain stains supported the diagnosis. A consult to the oncology service for systemic evaluation was arranged and magnetic resonance imaging (MRI) of the brain and orbits to rule out orbital involvement was ordered. A dilated fundus examination with B-scan ultrasonography was planned to rule out choroidal involvement.

Examinations were performed 1 day and 1 week postoperatively and were otherwise unremarkable. Conjunctival sutures were intact with no gaping; ofloxacin ophthalmic solution and prednisolone acetate ophthalmic suspension 4 times a day in the right eye were prescribed for the first week postoperatively, followed by a slow prednisolone acetate ophthalmic suspension taper over the next 4 weeks. The dilated fundus examination with B-scan ultrasonography found no posterior segment involvement. MRI findings with T1-weighted thin sections pre- and postcontrast axial and coronal images through the orbits were normal. Axial T2 and fluid-attenuated inversion recovery (FLAIR) images through the whole brain, along with T1W axial pre- and postimaging to the whole brain as well as sagittal T1-weighted imaging were normal. A thorough systemic evaluation for plasma cell dyscrasia with the oncology service found no systemic involvement.

At his postoperative month 1 examination, there was an increase in redness at the excision site and concern for recurrence versus postoperative inflammation. The patient was restarted on prednisolone acetate 1% ophthalmic suspension 4 times a day in the right eye with a slow taper to once a day in the right eye for 4 weeks, anterior segment photography was repeated, and the patient has been followed up closely without recurrence for the last 6 months.

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Discussion 

Plasmacytoma: background 

A plasmacytoma is a type of lymphoid tumor that has become modified to produce large amounts of immunoglobulin.2 With respect to the conjunctiva, plasma cell tumors may be divided into 3 categories: (1) a manifestation of systemic multiple myeloma; (2) a solitary extramedullary plasmacytoma; or (3) a plasma cell granuloma.12

Plasmacytomas secondary to multiple myeloma stem from plasma cell infiltration of the bone marrow, which can cause anemia, bone pain, pathologic fractures, renal insufficiency, and infection.13 Lesions from multiple myeloma are metastatic and represent approximately 1% of cancers.6 Besides periocular plasmacytoma such as conjunctiva, eyelid, and orbital plasmacytoma, other ophthalmic features of multiple myeloma include retinal vascular manifestations of hyperviscocity, corneal crystals, ciliary body cysts, and papilledema.14

A SEMP is less aggressive and can arise without evidence of a solitary myeloma of the bone or multiple myeloma.12 SEMPs arise from B-type lymphocytes that originate in the bone marrow, migrate to the peripheral lymphoid tissues, and then undergo plasmacytoid differentiation.15 Although the majority of SEMPs develop in the walls of the upper respiratory tract or nasopharynx,9 ocular involvement, although very rare, is possible. Because SEMP may be composed of premalignant B cells with no bone involvement, criteria for the diagnosis of SEMP include negative lymph node assessment, skeletal survey, bone marrow biopsy, and computed tomography.16 Urine examination for Bence Jones proteins, serum protein estimation, and serum protein electrophoresis may also be used to help exclude generalized disease.17 (Bence Jones proteins in the urine refer to the presence of kappa and lambda light-chain types and may result in kidney damage.18) SEMP can locally recur in 6% to 10% of cases with adequate initial treatment19 and may be a future indicator of multiple myeloma.20 In particular, a review found that 14.1% of non–upper aerodigestive extramedullary plasmacytomas convert to multiple myeloma.9

A plasma cell granuloma is a benign inflammatory lesion that is not associated with systemic abnormalities; granulomas typically are treated with excision alone.12

Ocular differential diagnoses of conjunctival plasmacytoma 

The differential diagnoses may be extensive and divided according to clinical and histopathologic appearance. Table 1 reviews possible differential diagnoses for a solitary bulbar conjunctival lesion in adults. Of note, conjunctival papilloma, conjunctival intraepithelial neoplasia, and squamous cell carcinoma may be described under the umbrella term of ocular surface squamous neoplasia (OSSN).

Table 1.
Differential diagnosesClinical appearanceHistopathologic featuresTypical management
Lymphoid tumor, including plasmacytoma21, 22Diffuse oval slightly elevated light pink (salmon-colored) mass typically conforming to the fornix contoursSheets of lymphocytes in the stroma or deep to Tenon's fasciaExcisional or incisional biopsy or radiation with observation; referral to internist or oncologist for systemic evaluation is also needed
Amelanotic nevus22, 23Well-demarcated lesion typically located in the interpalpebral bulbar conjunctiva near the limbus. Presence of small cysts in the lesion is a key sign in diagnosis. Pigmentation may change over timeNests of benign melanocytes in the stroma near the base layers of the epitheliumBaseline photography, observation every 6 to 12 months; surgical excision is elective or if suspicious for melanoma
Amelanotic melanoma22, 24, 25Painless, elevated lesion with prominent intrinsic vascularity and variable pigmentation that subsequently undergoes changes in size, shape, or colorVariably pigmented malignant melanocytes within the conjunctival stromaWide surgical excision (“no touch” minimal tumor manipulation) with cryotherapy and alcohol corneal epithelialectomy; may also be managed with mitomycin C
Granuloma12, 22, 26Elevated deep-red masses with a florid blood supplyGranulation tissue with chronic inflammatory cells, numerous small caliber blood vessels with damaged elastic fibersMay respond to topical corticosteroids but will require excision if persistent
Conjunctival myxoma27, 28Freely movable well-circumscribed yellow-pink translucent mass typically on temporal bulbar conjunctivaAbundant mucoid material with loose meshwork of reticulin fibers and a relatively small number of spindle- and stellate-shaped cellsComplete surgical resection with cardiac, endocrine, and family screening
Conjunctival papilloma21, 22, 29, 30Elevated pink fibrovascular fronds with starburst-like pattern of vasculature most commonly near the limbus; usually exophytic (sessile or pedunculated) or else inverted or mixed growth patternNumerous vascularized papillary fronds with acanthotic epithelial liningPeriodic observation; if large lesions cause symptoms or for cosmetic reasons complete excisional biopsy with supplemental cryotherapy is applied; topical interferon mitomycin C is employed if recurrence
Conjunctival intraepithelial neoplasia (CIN)21, 22, 30Fleshy, sessile or elevated gray-white lesion with a white plaque (due to secondary hyperkeratosis) that usually begins at the limbus. May develop a papillomatous appearance; may evolve into invasive squamous cell carcinomaPartial or nearly full thickness replacement of the surface epithelium by abnormal epithelial cells that lack normal maturation; localized in the epitheliumComplete excisional biopsy followed by supplemental cryotherapy; topical mitomycin C may also be used
Squamous cell carcinoma21, 22, 31, 32, 33Nodular, exophytic, gelatinous papillary lesion with loops of vessels without secondary pigmentary changes; larger, more elevated than CINMalignant squamous cells that infiltrate the basement membrane and have grown in sheets into the stromal tissueExcision with intraoperative control of the surgical margins with adjunctive cryotherapy; irradiation, topical mitomycin C may also be considered
Clinical appearance 

Lymphoid tumors, including plasmacytomas, present clinically as diffuse or localized slightly elevated smooth or multinodular fleshy pink masses that have been described as salmon-colored.22 Lymphoid tumors generally are located in the fornix or bulbar conjunctiva but may also present at the limbus; a mild vascular supply may be present, with larger dilated conjunctival vessels apparent in larger tumors.34 Biopsy is necessary for definitive diagnosis, and a systemic evaluation with laboratory and radiology testing is necessary to definitively determine if a plasmacytoma is a manifestation of systemic multiple myeloma or if it is a solitary extramedullary lesion.

Histopathology 

Upon gross examination lymphoplasmacytic lesions typically appear soft with poorly circumscribed borders.2 Histopathologically, sheets of large, uniform round cells with displaced nuclei, more abundant cytoplasm (consistent with mature plasma cells), clumped nuclear chromatic, prominent nucleoli, and variable mitotic activity are seen2 in the stroma or deep to Tenon's fascia. Immunohistochemical demonstration of monoclonal kappa or lambda light chains or heavy chains35 found in plasma cell tumors (IgA, IgD, IgG, IgM) typically are required, as extramedullary plasmacytomas may histologically appear similar to other tumors, such as lymphomas or undifferentiated carcinoma.36 Other histopathologic differential diagnoses include low grade B-cell non-Hodgkin lymphoma, such as lymphoplasmacytic lymphoma (which also may show plasmacytic differentiation), follicular lymphoma, and monocytoid B cell lymphoma.

Ocular and systemic management 

After histologic confirmation, a negative skeletal x-ray examination, bone marrow biopsy and aspiration, and laboratory results are required to identify true extramedullary plasmacytoma. Specifically, solitary extramedullary plasmacytomas manifest normal results for all of the following: blood sedimentation rate, complete blood count and blood smear, electrolytes and enzyme determination, serum and urine protein electrophoresis, immunoelectrophoresis and/or immunofixation in serum and in urine, and beta-2-microglobulin determination in serum with abnormal quantitative Ig determination in serum.9 In a quarter of patients, monoclonal gammopathy is present and disappears after complete treatment.37

Treatment for small or well-circumscribed solitary extramedullary plasmacytoma typically involves excisional biopsy20 with supplemental cryotherapy.34 Excisional biopsy is typically appropriate for tumors with a basal diameter equal to or smaller than 15 mm and preferred over incisional biopsy to avoid the risk of tumor seeding.22 After excision, cryotherapy is applied to the involved conjunctiva to reduce the risk of recurrence.22 Complete remission has been seen in lymphomas of low-grade malignancy, such as a solitary extramedullary plasmacytoma, with surgical excision alone.38 For larger lesions in which complete surgical resection is not possible, a more sizeable biopsy with histopathologic staging and possible amniotic membrane transplantation39 is completed, followed by chemotherapeutic or radiotherapeutic treatment.16 Although treatment with Rituximab immunotherapy alone may be effective and feasible40 and radiotherapy has been shown to be effective in treating extramedullary plasmacytoma,41 there is some evidence that patients who receive external beam radiotherapy alone have a higher risk of progression to multiple myeloma than with other treatment options.9 In some cases, periodic observation may also be a possible treatment option34 with consideration for photodocumentation to closely monitor for change.

Initial treatment for patients with systemic lymphoma typically involves chemotherapy with Rituximab.40 Radiotherapy, with total radiation doses administered ranging between 40 Gy and 60 Gy, may also be given, usually over a 4- to 6-week period.37 A bone marrow transplant may also be indicated; mean survival time in patients with multiple myeloma is 20 months.42

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Conclusion 

Although plasmacytomas of the eye and orbit are rare, eye care practitioners must be familiar with ophthalmic manifestations of these tumors and be aware that they may be associated with multiple myeloma. The ultimate diagnosis is made by biopsy and histopathologic examination of the tissue. Long-term follow-up, including periodic systemic evaluation, is required to detect local recurrence and establish that orbital involvement is not an early manifestation of multiple myeloma.

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References 

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PII: S1529-1839(09)00667-8

doi:10.1016/j.optm.2009.11.006

Optometry - Journal of the American Optometric Association
Volume 81, Issue 5 , Pages 234-239, May 2010

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