**Abstract**

Extramedullary (EM) plasmacytoma disease is an aggressive presentation at diagnosis and relapse for multiple myeloma (MM) patients. EM plasmacytoma is divided into two groups: the first group comprises tumors that extend directly from osteolytic bone lesions, while the second results from plasmacytoma infiltration into soft tissues, with no relation to the bone. Despite new therapies and monoclonal antibodies, the survival for patients with EM plasmacytoma is poor. The involvement of pleural effusion is uncommon in multiple myeloma.

**Keywords:** daratumumab, pleural effusion, extramedullary plasmacytoma, multiple myeloma, CD 38, PET/TC

## **1. Introduction**

Solitary plasmacytoma (SP) is an infrequent form of plasma cell neoplasm according to literature data, accounting for between 5 and 10% of all plasma cell neoplasms.

It is characterized by the presence of neoplastic monoclonal plasma cells that do not have systemic distribution but gather in limited locations even if there is no systemic proliferative plasma cell disease.

We can divide it into two groups: solitary bone plasmacytoma (SBP) and extra medullary plasmacytoma (EMP).

When the localization is prevalent in the bones of the axial skeleton, skull type, vertebrae, etc., we speak of solitary plasmacytoma of the bone (SBP), while EMP, as a localization, is frequent in the nasal cavities and in the nasopharynx.

The mean age of patients with SBP or EMP, with a male–female ratio of SP 2:1, is 55 years.

With advancing age, the incidence rate increases exponentially while maintaining a lower incidence compared to multiple myeloma (MM).

In the black population, the impact of the SP is about 30% higher than that in the white population [1].

A better definition of the tumor mass can be obtained with the fluorodeoxyglucose-positron emission tomography (FDG-PET) or positron emission tomographycomputed tomography (PET-CT) [2] that allows direct visualization of the tumor burden; combining the morphological images of the CT scan with a particular molecular process (depending on the radiopharmaceutical injected such as a glucose analogue, which is the most widely used) allows to evaluate the response to treatment and the prognosis of different cancers.

The limit of the skeletal X-ray investigation of the whole body (WBXR) is represented by showing only osteolysis related to the presence of MM cells, while the FDG-PET allows to view the tumor load.

Obviously, this investigation is not without limitations; one of which is the false negative or false-positive result, which is possible if inflammatory or infectious processes are in progress or if subcentimetric lesions cannot be detected by FDG-PET.

Aid is provided by the combined CT component, which provides higher resolution bone images than those obtained with normal radiography.

Through a direct anatomical correlation of FDG uptake foci.

The systematic review reported by Van Lammeren-Venema et al. [3] also compared FDG-PET and FDG-PET/CT with WBXR and CT.

The detection rate of FDG-PET/CT, compared with WBXR, ranged from 1.27 to 1.45; specificity was low (29–50%) and sensitivity ranged from 67 to 100% when using WBXR as a reference test. Regelink et al. mentioned that FDG-PET underestimates rib lesions, as they could be detected by low-dose CT integrated into PET.

A limitation, to date not resolved, is the detection of cranial lesions that FDG-PET/CT does not detect due to the high absorption of FDG in the brain, while the identification of extramedullary disease was satisfactory with FDG-PET; this has been reported consistently in studies comparing FDG-PET/CT with WBXR.

In addition to FDG that is specific to glucose metabolism, other PET radiopharmaceuticals have been developed to visualize various biological processes; among these, we can mention 18F fluoride being reevaluated for skeletal imaging and the 11C-methionine amino acid analogue and 11C-choline, an analogue precursor of phosphatidylcholine, one of the main constituents of membrane lipids, which to date have only been evaluated in small series of patients with MM.

Multiple myeloma [4] is a clonal malignant plasma cell neoplasm that despite the development of new therapies that have improved the depth and duration of responses as well as survival, to date, remains incurable in most cases for many patients.

Understanding the biology of disease, technological advances, such as next-generation sequencing techniques, have shown that the disease is genetically extremely heterogeneous, and this has allowed us to stratify patients, based on risk, into different disease groups. This can significantly translate into the choice of therapy and clinical results.

Simultaneously with these new acquisitions, the therapeutic scenario has been completely revolutionized by the discovery of new therapeutic agents, including immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide; proteasome inhibitors (PIs) including bortezomib, carfilzomib and ixazomib; monoclonal antibodies (MAbs) including daratumumab and elotuzumab; and histone deacetylase inhibitors such as panobinostat, which have helped improve the overall survival of patients with this disease.

The use of many new therapeutic agents, in addition to increasing therapeutic choices, has also changed our therapeutic reference models; in fact, over the years, the treatment of patients with this pathology has mainly been based on high-dose radiation, but today, in consideration of the new drugs available to us, studies are needed to evaluate their use and benefit also in this category of high-risk patients.

**85**

**Table 1.**

*Pleural Effusion Secondary to Multiple Myeloma: Is Daratumumab an Effective Treatment?…*

A 58-year-old woman was diagnosed asymptomatic Multiple Myeloma Ig G K,

She first presented in March 2018 because about 15 days before she was admitted to the nephrology department for acute renal failure, macrohematuria, hydrone-

For confirmation during hospitalization, the laboratory tests of the monoclonal

At the evaluation of the bone biopsy, plasma cell clonality was equal to 10–40%. At the phenotypic analysis and morphological examination, plasma cell infiltrate

The karyotype analysis was 46 XX normal karyotype, and the FISH study

Therefore, we asked the patient to visit the clinic for periodic checks.

blood tests and instrumental tests TB CT and MRI were performed.

abdominal-pelvic lymph node stations, no free abdominal fluid."

that concentrically englobes the aorta and pleural effusion."

Whole-body MRI showed no bone lesions, and the total body CT was negative.

After one year from diagnosis, in May 2019, she reported back pain for which

The total body CT showed the following: "In a context of widespread reduction in calcium content, suspicious osteostructural alterations due to secondary disease localization of the skeletal segments included in the study volume are not appreciated. Apex cuneiform deformation of the anterior trunk of D12, widespread spondyloarthrosis manifestations. No focal tomodensitometric alterations of current pathological significance affecting the lung parenchyma bilaterally. Nonilo-mediastinal and laterocervical lymphadenomegaly. Non-pleural-pericardial effusion. No gross changes affecting the abdominal parenchymatous organs, distended bladder with regular walls, no adenomegaly at the level of the main

Unlike the CT, the MRI of the abdomen showed the following: "collapse of D12 and pathological tissue with a paravertebral site with abdominal tissue formation

The MRI of dorsal and lumbar spine showed the following: "at the level of the interbody space D11–D12, presence of posterior median disc protrusion, at the level of the interbody space D12–L1, presence of protrusion of the annulus fibrosus with

> **Immunophenotypic study in flow cytometry Method used direct immunofluorescence**

> > Result

The spinal cord presents regular morphology and no pathological signal.

Clonal myeloma plasma cells: CD 138+ CD 38++ CD19-CD56+ bright CD 45 neg = 24%

Blood chemistry tests revealed that protein electrophoresis showed a monoclonal spike (M spike) 1 g/dl: IgG tests 1000 mg/dl, IgM 34 mg/dl, IgA 44 mg/dl, serum kappa light chains 294 mg/dl, serum lambda light chains 24 mg/dl, urine kappa light chains 187 mg/L, urine lambda light chains <4.7 mg/dl, FLC ratio 58, beta 2 microglobulin: 4.3 mg/L, Hb 13 g/dl, normal creatinine and calcium, protein-

*DOI: http://dx.doi.org/10.5772/intechopen.95659*

stage II (International staging system - ISS).

Physical examination was negative.

uria 0.8 g/24 h, and microalbuminuria 68 mg/L.

showed TP53 in 35% of the nuclei analyzed.

**2. Case introduction**

phrosis, and renal colic.

component was sent to our clinic.

was equal to 24% (**Table 1**).

posterior median expression."

*Phenotypic analysis of bone biopsy.*

Antigens studied: CD19, CD38, CD 138, CD 56, CD 45

*Pleural Effusion Secondary to Multiple Myeloma: Is Daratumumab an Effective Treatment?… DOI: http://dx.doi.org/10.5772/intechopen.95659*
