A Case Series of Aggressive Orbital Plasmacytomas

Orbital plasmacytoma accounts for less than 1% of total orbital lesions. Sixty-five percent of orbital plasmacytoma are carrying a diagnosis of multiple myeloma (MM), which arise from systemic effects of increased blood viscosity or plasma cell (PC) infiltration into ocular tissues [1]. Orbital involvement in MM is a very rare finding, comprising only 1 in 200–800 cases [2]. We hereby present 2 cases of orbital plasmacytoma, a rare orbital malignancy with unsatisfactory outcomes.

A 41-year-old woman presented with left unilateral proptosis for a 2-month period (shown in Fig. 1a). She had no systemic complaints or sought any treatment before. Ophthalmic examination revealed left non-axial proptosis with a smooth, firm, non-tender palpable mass in the superotemporal orbit. Best corrected visual acuity was 6/30, and ocular motility was restricted to all directions. Orbital CT scan demonstrated an extraconal homogenously solid mass at the superotemporal aspect of the left orbit, compressing the globe, the optic nerve, and superior and lateral rectus muscle with obliteration of the left lacrimal gland. There was bone destruction at the orbital roof and lateral wall (shown in Fig. 1a). A malignant lacrimal gland tumor with intracranial invasion was suspected, then an incisional biopsy was carried on. The histology from biopsy showed proliferation of PCs with intranuclear pseudoinclusion of Dutcher bodies. Mitotic activity was also found. Immunohistochemical stains showed monoclonal Kappa light chains with cluster of differentiation 38 (CD38) and CD138 positivity (shown in Fig. 1b). The diagnosis of orbital plasmacytoma was confirmed.

Later, systemic evaluation discovered a lump on her chest which biopsy showed was a malignant round-cell tumor with differential diagnosis including hematolymphoid malignancies. Immunohistochemistry (IHC) showed membranous staining for CD38 and CD138, confirming plasmacytoma. She also complained that her proptosis became more prominent with worsening blurry vision. Her left vision was light perception with total restriction of ocular movements, positive relative afferent pupillary defect, hyperemic, and indistinct margins of the optic disc. Biochemical laboratory results showed hyperproteinemia, hypoalbuminemia, decreased albumin/globulin ratio, and hypergammaglobulinemia with monoclonal appearance (protein total 11 g/dL; albumin 3.29 g/dL; albumin/globulin ratio 0.4; γ-globulin 6.22 g/dL or 56.5%). Immunoelectrophoresis showed apparent elevation of IgA level (lgA 5,090 mg/dL). Immunofixation patterns showed IgAκ myeloma with free κ-light chains (shown in Fig. 1c). Bone marrow aspiration and biopsy revealed a normal distribution of hematopoietic cells with 2% PCs and negative immunohistochemical staining. A skeletal survey revealed multiple destructive lytic lesions in the left orbit and bilateral frontal bone (shown in Fig. 1d).

This patient was confirmed as having IgA-type MM with multiple secondary plasmacytomas. She was in Durie-Salmon Staging System (DSS) stage III and planned for 6 cycles of chemotherapy with VAD regimen (vincristine 0.4 mg, doxorubicin 15 mg, and dexamethasone 40 mg per day for four consecutive days). Unfortunately, she presented to the emergency room with loss of consciousness before chemotherapy was administered. The brain CT scan demonstrated solid tumor in the superotemporal orbit, which compressed the left hemisphere, causing subfalcine, uncal herniation and cerebral edema. She died within 7 days after admission to ER, 2 months after diagnosis, or 5 months after her initial symptoms.

A 45-year-old man presented with progressive right eye protrusion and blurred vision over 2 months (shown in Fig. 2a). He also complained loss of weight. Agitation and uncooperative behavior were noted. Visual acuity was light perception with non-axial proptosis, inferior globe displacement, and restricted eye movement in all directions. A solid, smooth, fixated, and non-tender mass in the superior orbit and frontal area was present. No lymph node involvement was noted. Orbital CT revealed a hyperdense lesion, involving both intraconal and extraconal compartments, occupying the superior aspect of the right orbit and right frontal sinus, infiltrating the right frontal lobe and right superior rectus muscle. There were bone destructions and calcification around the lesion (shown in Fig. 2b–d).

The histology from biopsy showed round-shaped tumor cells with eccentrically located nuclei and Dutcher bodies. Immunohistochemical staining showed positive results for CD38, CD138 and negative results for CD3, CD20 (shown in Fig. 2b). Based on morphology and IHC staining, this tumor was consistent with orbital plasmacytoma. The chest X-ray and abdominal ultrasound showed unremarkable findings. Unfortunately, the patient died before systemic MM workup was performed. He died within 10 days after diagnosis or 3 months after his initial symptoms.

The first case presented with orbital abnormalities as the initial presentation of MM. Both cases came with a chief complaint of unilateral proptosis. Proptosis appears to be the most common symptom of orbital plasmacytoma. Other symptoms included palpable lump or swelling, diplopia, blurred vision, orbital pain, ptosis, and redness [1, 3]. Those 2 patients also had ocular motility limitation and optic disc edema as a result of metastatic mass located posterior to the globe which was compressing the extraocular muscles and applying pressure to the optic nerve [4]. Orbital symptoms were mostly unilateral. Orbital plasmacytoma also has a gradual onset of symptoms, 2 months on average, similar to our patients [1, 3]. Fatigue, bone pain, and fractures, particularly in the back and chest, recurrent infections, easy bruising and bleeding, and loss of weight could be found as presenting features of MM [4]. Orbital plasmacytoma symptoms are nonspecific and similar to other diseases; thus, a complete examination should be done at the initial visit.

Orbital plasmacytoma is usually locally aggressive with involvement and destruction of adjacent structures. Bony destruction appears to be common [5]. According to Burkat et al. [1], the lesion of orbital MM was mostly located in superotemporal quadrant involving posterior aspect of the orbit and usually extraconal. Similar to our cases, this superotemporal location could be due to a predilection for the lacrimal gland in MM metastasis, receiving rich blood supply, or the sphenoid bone having the most developed and extensive marrow in this region [1].

Orbital CT and magnetic resonance imaging, independently or together, provide valuable information on localizing the origin and extension of the tumor, including bone destruction. Tai et al. [6] recommended CT scan as the imaging modality of choice in orbital MM. CT has advantages in the examination of bony or other high-density lesions, while MRI is advantageous for delineating soft tissue processes, thus can highlight differences in cellular content of lesions and the local surrounding tissues [5].

Diagnosis of orbital plasmacytoma needs histopathological confirmation of the nature of the orbital lesion, which demonstrates a dense monomorphous infiltrate of PCs [5]. The PCs vary from binucleated to multinucleated and have larger size than average. The nucleus is eccentrically located with cartwheel chromatin appearance. Intranuclear pseudoinclusion (Dutcher bodies) and intracytoplasmic inclusions are frequently encountered [7]. IHC will help confirm the lesion as orbital plasmacytoma. Ajise et al. [8] stated that CD138 and CD38 are sensitive and specific markers for PCN, like we have seen in our cases. Incisional biopsy was preferred in order to attain more representative portion of tumor tissue for histopathology and IHC examination.

Once plasmacytoma was confirmed, the next step is to determine whether it is a primary lesion arising from the orbital soft tissue or secondary plasmacytoma due to MM. Galea [9] reported that in 75% of cases, orbital involvement is the first manifestation of systemic MM. An active MM is diagnosed with current diagnostic criteria (shown in Fig. 3). A prompt investigation for systemic involvement is needed as the treatment and prognosis differ between the two [10]. National Comprehensive Cancer Network guidelines recommend the diagnostic studies including bone marrow aspirate and biopsy, laboratory, and skeletal survey [6]. Peripheral smear may show rouleaux formations due to elevated serum proteins [11]. Increased BUN and creatinine, acidosis, and electrolyte imbalance indicate real failure [10]. Primary plasmacytoma has normal uninvolved immunoglobulin levels with a lower level of M protein compared to MM. Hypergammaglobulinemia is present in 85% of cases of MM [11]. Electrophoresis reveals a monoclonal protein (also called M protein) detected in the serum or urine. M protein is composed of light chain (Bence-Jones protein) and heavy chain (IgG, IgA). The most common MM subtype is IgG, followed by IgA. Clonality is confirmed by kappa or lambda light-chain restriction. Zuo et al. [12] reported that 87.5% of the cases of MM displayed Ig light-chain restriction, with Igλ type predominant.

According to National Comprehensive Cancer Network guidelines, whole-body low-dose CT or fluorodeoxyglucose positron emission tomography CT (PET scan) is recommended for initial diagnostic workup of patients suspected to have MM or solitary plasmacytoma. Skeletal survey is less sensitive in detecting osteolytic lesions but acceptable in certain circumstances. Skeletal survey consists of conventional X-rays of multiple skeletal sites including the skull, spine, pelvis, chest, femoral, or humeri. The imaging usually demonstrates multiple, well-circumscribed, lytic and punched-out, round lesions. The pattern of lytic or punched-out radiolucent lesions on the skull has been described as resembling “raindrops” hitting a surface and splashing [10]. However, imaging alone cannot distinguish from other malignancies and requires histologic evidence for diagnosis.

Due to the rarity of the disease, there are no randomized studies about the best treatment approach, and data reported in the literature are controversial. Treatment option for primary orbital plasmacytoma is radiotherapy, while secondary plasmacytoma requires systemic chemotherapy. Surgery is limited to adjunctive therapy and may be performed if a lesion causes structural instability or neurological compromise. The choice of surgery needs to be tailored to each patient based on systemic condition, location, and tumor extension [10].

In conjunction with a hematologist-oncologist, patients with active MM are initially treated with primary therapy and followed by high-dose chemotherapy with autologous stem cell transplant in transplant-eligible patients. Chemotherapy is used to damage or control myeloma cells. Conventionally, VAD (vincristine, doxorubicin [Adriamycin], and dexamethasone) chemotherapy has been used to decrease the tumor burden in MM as preparation for transplantation. VAD is now considered suboptimal treatment. Current standard for MM treatment includes proteasome inhibitors (bortezomib), immunomodulatory drugs (thalidomide and lenalidomide), histone deacetylase inhibitors, and monoclonal antibodies [10].

The median duration of primary orbital plasmacytoma progression to develop MM was 2–3 years. Rajkumar [13] also reported that primary orbital plasmacytoma has 10% risk of progressing into MM within 3 years; thus, regular follow-up is needed. The current 5-year survival rate is around 35% and 10-year survival is only about 10% [11]. Andriandi et al. [14] reported that survival rate of MM was lower in patients with higher International Staging System stage. The study also found that nearly all patients with the disease experienced relapse and eventually succumbed to refractory disease, even after treatment. The first patient was diagnosed as IgA-type MM which had a poor prognosis due to underlying cytogenetic abnormalities. Wang et al. [15] reported that in IgA-type MM, 33.3% of patients have 17p deletion and chromosome 1q21 gain abnormalities. She was also on stage III DSS, which had the lowest survival rate. The survival rate of MM was lower in patients with higher DSS staging. In stage III DSS, the survival rate is only 23 months compared to 60 months and 41 months in stage I and II, respectively [16].

Orbital plasmacytoma is a rare orbital malignancy and is commonly secondary to systemic MM. Ophthalmologists must have a high index of suspicion as it has a nonspecific presentation. The most common symptom is proptosis, occurring unilaterally at more than 40 years of age. Orbital CT scan is the imaging modality of choice as it can demonstrate soft tissue lesions with bone destruction, commonly in superotemporal quadrant. A biopsy is mandatory to establish a definitive diagnosis. Immunohistochemical staining confirmed positivity for CD38 and CD138. A thorough systemic workup should always be performed to determine whether it is a primary or secondary plasmacytoma, which guides further management. Radiation therapy is the recommended treatment for primary orbital plasmacytoma, while chemotherapy for MM. Orbital plasmacytoma, as an aggressive form of PCN, has poor prognosis. Thus, ophthalmologists should consider orbital plasmacytoma as one of the differential diagnoses in orbital tumors. Appropriate treatment strategy must be implemented immediately as the disease has very aggressive behavior.

Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent was obtained from the patient’s next of kin for publication of the details of their medical case and any accompanying images.

The authors have no conflicts of interest to declare.

The authors have no sponsors.

Nizma Permaisuari was involved in writing the manuscript and performing a review of the literature. Neni Anggraini and Wulyo Rajabto were involved in the care of the patient in case 1, while Mutmainah Mahyuddin was involved in case 2. Neni Anggraini, Mutmainah Mahyuddin, Evelina Kodrat, and Wulyo Rajabto were involved in critical review of the manuscript.

All data in this study are included in this article. Further inquiries can be directed to the corresponding author.