Proteinaceous Lymphadenopathy Masquerading as Malignancy: a Rare Case Presenting a Diagnostic Dilemma

Abstract

Proteinaceous lymphadenopathy (PLD) is a rare poorly defined, underrecognized entity of uncertain etiology, characterized by massive deposition of amorphous, acellular, eosinophilic, PAS-positive material within an enlarged lymph node. We report an unusual case of a 46-year-old female with a large abdominal lump in the left lumbar region with inguinal lymphadenopathy. Contrast-enhanced computed tomography (CECT) showed multiple variable-sized lobulated non-enhancing soft tissue attenuated masses showing multiple peripheral and central calcific foci in the right para-aortic, bilateral iliac region, pelvis on the left side and left inguinal region. No evidence of any abnormal hypermetabolic focus was found in the neck, chest, abdomen, and pelvis on fluorodeoxyglucose positron emission tomography. A large, well-defined, non-FDG avid mass lesion with significant central and peripheral calcification in the left iliac fossa, abutting the descending colon, was seen. A biopsy of left-sided inguinal lymph nodes revealed large masses of an amorphous, acellular, eosinophilic material with areas of mature lymphoid cell aggregates interspersed between the pink amorphous materials. A final impression of proteinaceous lymphadenopathy was given. Proteinaceous lymphadenopathy is a benign condition with often a large mass masquerading as malignancy. It is a major therapeutic challenge for pathologists and clinicians. Histopathologists need to be vigilant in such cases and be aware of the morphological appearances in such cases.

Introduction

Proteinaceous lymphadenopathy (PLD) is a rare poorly defined, underrecognized entity of uncertain etiology. It is characterized by massive deposition of amorphous, acellular, eosinophilic, PAS-positive material within an enlarged lymph node [1]. It is not associated with clonal immunoglobulin or amyloid deposition. This hyalinization affects the lymph nodal architecture and its function. Hyaline deposition of the lymph node is a rare condition and is often a nonspecific finding [2]. We report here an unusual case of an elderly female with proteinaceous lymphadenopathy creating a diagnostic challenge for pathologists and a therapeutic challenge for clinicians.

Case Report

A 46-year-old female came to the surgical outpatient department with pain in the abdomen, vomiting, and constipation since 10 days. The patient was a known case of diabetes with hypertension with raised blood sugar and HbA₁C of 9.7%. No history of fever, weight loss, or any other significant ailment was given. On examination, a large abdominal lump was palpated in the left lumbar region with inguinal lymphadenopathy. A provisional diagnosis of lymphoma/soft tissue sarcoma was made. Her complete blood count was within normal limits with raised high-sensitivity C-reactive protein. Her liver and kidney function tests were within normal limits.

Ultrasonography abdomen showed multiple enlarged, well-echoic lesions along the common iliac, left external and internal iliac region in the left half of the pelvis and in the anterior aspect of the proximal thigh showing areas of calcification. Differentials of tuberculosis/calcified lymphoma or calcified mucinous deposits were made.

Contrast-enhanced computed tomography (CECT) showed multiple variable-sized lobulated non-enhancing soft tissue attenuated masses showing multiple peripheral and central calcific foci in the right para-aortic, bilateral iliac region, pelvis on the left side and left inguinal region, largest measuring 13 × 7.1 cm in the left para-aortic region. The left pelvic mass was closely abutting the descending colon. In the post-contrast study, the masses showed no significant enhancement (Fig. 1). Differentials of lymph nodal masses, tuberculosis, Castleman’s disease, or lymphoma were given.

Fig. 1.

CT images showing multiple variable-sized lobulated non-enhancing soft tissue attenuated masses. a Non-Contrast, axial view. b Contrast, coronal view

Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET CT) revealed multiple mostly conglomerate, well-marginated, retro-peritoneal, non-FDG avid calcified masses likely mesenteric masses of different sizes and with no significant FDG uptake in para-aortic and bilateral iliac region. A large, well-defined, non-FDG avid mass lesion with significant central and peripheral calcification in the left iliac fossa, abutting the descending colon, was seen. A large, partly necrotic, non-FDG avid mass with small calcific foci in the left inguinal region along with a few small, non-FDG avid, non-calcified left pelvic side wall nodes was noted. No evidence of any abnormal hypermetabolic focus was found in the neck, chest, abdomen, and pelvis.

A biopsy of left-sided inguinal lymph nodes was done and sent for histopathological examination. We received multiple friable grey-brown to grey-white soft tissue bits, measuring 6 × 5 × 2 cm. Histopathological examination revealed large masses of an amorphous, acellular, and eosinophilic material with areas of mature lymphoid cell aggregates interspersed between the pink amorphous material. The material is also seen deposited around blood vessels. Also seen are many multinucleated giant cells, focal calcification, and new bone formation in the surrounding tissue (Fig. 2). Possibility of amyloid lymph node/proteinaceous lymphadenopathy was considered. The amorphous material was negative for Congo red viewed with and without polarized light, ruling out amyloid and positive for PAS. Ziehl–Neelsen stain for acid-fast bacilli was negative. An immunological workup was advised. Immunoglobulin IgG levels were markedly raised to 2340 mg/dl. However, IgG antibodies to soluble substance (SS) A(Ro) and B(La), antinuclear antibodies, and rheumatoid factor came out to be negative. Viral markers were negative. A final impression of proteinaceous lymphadenopathy was given. The patient denied surgical resection of the mass lesion and was managed symptomatically. She is taking regular treatment for diabetes and hypertension. She has been followed for 1 year and is well without any change in the size of the lesion.

Fig. 2.

a Masses of acellular, eosinophilic material with areas of mature lymphoid cell aggregates interspersed (Inset). b New bone formation (H&E, × 100)

Discussion

Osborne et al. in 1979 described PLD as a rare non-specific disorder involving lymph nodes. Its incidence increases with age and is often present in the stroma of pelvic or abdominal nodes [1]. The index case is a 46-year-old female with left inguinal lymphadenopathy.

It is usually associated with hypergammaglobulinemia, rheumatoid arthritis, or systemic sclerosis. This condition can be idiopathic, and it has also been reported in infective conditions like HIV or Kikuchi’s disease. It may affect the nodal function, and rarely, it may calcify [2]. The present case showed hyperimmunoglobulinemia and calcification, ruling out rheumatoid arthritis and systemic sclerosis.

PLD of an unknown etiology is an extremely rare condition, and relatively little is known about its clinical manifestations or its response to therapy. The conditions associated with rheumatological conditions show a better clinical response after the treatment of arthritis [3].

It is also known as hyaline deposition of the lymph node. Hyalinization seems to be one of the major events that affect the nodal filtration function and ruin the node with aging [2]. Hyalinization of lymph nodes can also be seen following long-standing inflammatory conditions such as sarcoidosis or tuberculosis which should be kept in mind when evaluating such conditions. The present case showed no features of sarcoidosis or tuberculosis.

Microscopically, it is characterized by extracellular eosinophilic material resembling amyloid but Congo red is negative and there is concentric arrangement of an amorphous, eosinophilic material around blood vessels with hyaline sclerosis of small- and mid-sized vessels of lymph nodes as seen in the index case [4].

Heterotopic ossification (HO) is a benign condition that occurs owing to bone deposition in the extraskeletal soft tissues, mostly in the extremities and rarely in the mesentery. It is believed to occur after repeated infectious or traumatic insult, as a result of aberrant tissue repair and is increasingly recognized as a common complication of trauma, surgery, and any other local or systemic insults. On CT, immature bone is not well organized and may be more difficult to discriminate from calcifications. The present case showed new bone formations with giant cells, and CT showed calcific foci. On an extensive search of the literature, we could not find any other case of PLD with HO.

Michaeli et al. proposed the term “angiocentric sclerosing lymphadenopathy” for lymphadenopathy with diffuse depletion of lymphoid cells and massive eosinophilic deposits concentrically arranged around blood vessels with no evidence of clonality [5].

The authors have suggested that PLD deposits might represent polyclonal immunoglobulin due to the polyclonal pattern of staining of PLD deposits by kappa and lambda immunohistochemical stains [4]. It can be distinguished from monoclonal non-amyloid light chain deposition disorder, multiple myeloma, and amyloidosis based on pathological, immunological, and clinical findings [6].

The extracellular material seen in PLD may resemble collagen sclerosis grossly and microscopically. It is always challenging for histopathologists as differentials like nodular lymphoma with lymph node sclerosis and amyloid deposition have to be excluded as in the current case. This distinction might be impossible in a small biopsy that contains only eosinophilic material. Nodules in lymphoma are composed of a monomorphic population of lymphocytes permeating the eosinophilic material in contrast to PLN which is characterized by a variable number of residual normal follicles, the mixture of lymphocytes, and plasma cells scattered within homogenous eosinophilic material as seen in the index case [7].

The etiology of PLD is unclear but it is likely to be triggered by an infectious or inflammatory process as historically, it has shown a response to steroid therapy [6]. However, in view of the common association of PLD with autoimmune disorders, such as rheumatoid arthritis and chronic infections, it has been found that the response to prednisone may be related to underlying disease, and PLD by itself may be a reactive condition to an underlying chronic inflammatory disorder [4].

Conclusion

Proteinaceous lymphadenopathy is a benign condition with often a large mass masquerading as malignancy. It is a major therapeutic challenge for pathologists and clinicians. Histopathologists must be vigilant in such cases and aware of this underreported and underrecognized pathological entity.

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Conflict of Interest

The authors declare no competing interests.