Igg4 Pseudo tumors Mimicking Urologic Malignancies: Comprehensive Review and Management of a Rare Infiltrative Upper Tract Lesion

Clinical History

A 66-year-old male was referred for urologic evaluation of an incidentally found left renal collecting system mass noted on magnetic resonance imaging (MRI) of his abdomen for surveillance of a benign appearing pancreatic cyst. This MRI noted a new 7 x 3.8 x 3.8cm infiltrating hypoenhancing mass replacing the left renal sinus and extending along the proximal left ureter causing moderate left hydronephrosis concerning for urothelial cell carcinoma. A subsequent computed tomography intravenous pyelogram (CT IVP) demonstrated a slightly enhancing left renal mass and delayed imaging illustrated filling defects in the left renal collecting system (Figures 1 & 2). At his office visit, he endorsed mild left flank pain. He denied any other urologic symptoms, including hematuria. Social and family history was remarkable for a 12 pack-year smoking history and no family history of renal failure or malignancy. Physical exam was unremarkable. Laboratory analysis was notable for a creatinine of 0.8, white blood cell count of 7.7, and atypical cells noted on his urine cytology. Of note, the patient had an abdominal CT imaging 18 month prior showing a normal left kidney and ureter except for a 4mm left upper pole nephrolith and multiple distal ureteral stones less than 6mm in size. At that time, the patient underwent an uncomplicated left ureteropyeloscopy, laser lithotripsy, and left ureteral stent placement by an endourologist.

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Figure1: Coronal Images of CT Intravenous pyelogram, arterial phase, demonstrating a slightly enhancing left upper tract collecting system/renal mass.

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Now, due to the concerning presentation additional evaluation was performed including a cystoscopy, left retrograde pyelogram, and direct ureteroscopic visualization. The pyelogram showed narrowing of the left renal pelvis and limiting opacification of the collecting system. A left ureteropyeloscopy was performed to rule out an intrinsic collecting system lesion. This demonstrated normal appearing urothelium with narrowing of the renal pelvis and collecting system in a similar location seen on the pyelogram, consistent with extrinsic compression. Left ureteral barbotage and bladder washings were performed showing normal cytology. A positron emission tomography-computed tomography (PET-CT) noted radiotracer activity in the region of the known left renal mass (max SUV (standardized uptake value) 8.9) potentially representing malignancy, as well as a PET avid left cervical lymph node (max SUV 5.36). A core needle biopsy with CT guidance was performed showing reactive benign lymphoid tissue. For improved tissue sampling, fine-needle aspiration and excisional biopsy of the cervical lymph node was then obtained. Pathology results noted reactive follicular hyperplasia and focal nodular para-cortical hyperplasia. After appropriate counseling of the options, the patient ultimately elected for a surgical excision due to the risks of malignancy, progressing left renal obstruction and pain, and delay in diagnosis. An adrenal- sparing left radical nephrectomy and paraaortic lymph node dissection was performed through a left subcostal incision. The estimated blood loss was 180cc with an operative time 165 minutes. The patient had an uncomplicated post- operative course and was discharged on post-operative day 3. He remains free of disease recurrence at 65 months from his surgery.

Pathologic Findings

Pathologic evaluation of the surgical specimen demonstrated an ill-defined multinodular mass (6.8 x 5.9 x 5.5cm) with a glistening, homogeneous pink-yellow surface. The mass grossly did not invade into the calices, renal pelvis or ureter; and was noted to replace much of the renal sinus adipose tissue. Lastly, the mass was noted to not involve kidney parenchyma, renal vein or artery. The para-aortic lymphoid tissue was noted to have thirteen benign lymph nodes, the largest 1.4cm, with no suspicious areas concerning for malignancy.

Microscopically it was noted to have a lymphocytic infiltrate and scattered reactive germinal center. It stained grossly positive for CD 20, CD 10, and negative for BCL 2. Also noted were several areas of dense, hyalinized fibrosis that assumed a “storiform” pattern: a cartwheel appearance of the arranged fibroblasts and inflammatory cells. All of these findings are typical histopathologic features of an IgG4 related inflammatory pseudotumor [1].

Review of the Literature

IgG4-related disease is characterized by extensive IgG4- positive plasma cells and T-lymphocyte infiltration of various organs. Inflammatory pseudotumor as a manifestation of IgG4-related disease, with or without sclerosis, in the genitourinary tract is a rare entity and can often mimic a malignant or inflammatory process prior to definitive diagnosis [4]. Our literature review yielded a collection of case reports describing IgG4-retated pseudotumor of the genitourinary tract, as described below.

Renal

Renal lesions in IgG4-related disease are rare and most commonly manifest as multiple wedge-shaped or nodular cortical lesions in one or both kidneys. IgG4-related renal lesions can mimic renal cell carcinoma or transitional cell carcinoma in uncommon cases of a single unilateral mass, such as a renal lesion or focal unilateral renal pelvic wall thickening. Wang et al reported a case with CT/PET/MRI findings of a renal pelvic mass and diffuse lymphadenopathy, concerning for metastatic renal carcinoma. After completion of a nephroureterectomy with retroperitoneal lymph node dissection, the final pathology was determined to be an IgG4- related lesion. She completed a year of high dose steroid therapy for residual lymphadenopathy, with improvement in signs and symptoms [5]. Park and Kim reported a case of a 5cm renal pelvis mass, the mass was not biopsied prior to a right nephroureterectomy. Pathology subsequently revealed IgG4-related disease pseudotumor and not an upper tract urothelial cell carcinoma. Serum IgG4 levels were normal 1 month post operatively and no additional treatment was rendered [6].

Samji et al presented a case study where a patient demonstrated a suprarenal mass inseparable from the kidney. A CT-guided biopsy of the mass was performed. Hematoxylin and eosin stain sections of the core biopsy showed fibro adipose tissue with extensive fibrosis, scattered lymphoid follicles and areas of plasma cell-rich lymphoplasmacytic infiltrates. By immunohistochemistry, the IgG4 to IgG ratio was greater than 0.4 and there were more than 10 IgG4- positive plasma cells per high power field. There was no evidence of lymphoproliferative disease. The patient was tested retrospectively for IgG4 level, which was elevated to 140.7 mg/dl (normal range: 4-86 mg/dl). The patient started prednisone 20mg daily. One month after initiating steroid therapy, interval CT demonstrated decrease in the soft tissue masses [7]. This is a significant biopsy finding as it confirmed diagnosis while preventing the patient an invasive surgical procedure to rule out malignancy.

More recently, Tawhari et al. reported a case where a 55-year-old woman was found to have two ipsilateral renal masses with associated lymphadenopathy on evaluation for acute renal insufficiency. The masses were biopsied and found to be comprised of infiltrative IgG4 positive plasma cells. Treatment with corticosteroids resulted in resolution of renal masses and lymphadenopathy, however the patient ultimately progressed to end-stage renal disease requiring hemodialysis [8]. These are several instances of IgG4 pseudotumors mimicking renal and upper tract malignancies in which the lesions were biopsied and confirmed the diagnosis, thus negating a more invasive surgical procedure associate with longer recovery and higher patient morbidity.

Prostate

IgG4 related pseudotumor is also a consideration in prostate lesions. It can manifest as diffuse prostatitis or with focal lesions, mimicking prostatic adenocarcinoma. In 2023, Lee et al. published a case report describing a patient with a known history of IgG4-RD of the lacrimal gland with persistently elevated serum IgG4 after treatment. Rectal MRI performed for unrelated reasons was notable for an incidental PI-RADS 5 lesion, suspicious for primary prostatic adenocarcinoma. Serum prostate specific antigen (PSA) was normal at 1.5 mg/dL (0-4 mg/dL). Differential diagnosis of periprostatic inflammatory IgG4-RD was considered and subsequently proven on MRI-ultrasound fusion targeted biopsy [9].

Testicular/Paratesticular

Recent publications have postulated an association between paratesticular fibrous pseudotumor (PFP) and IgG4-related sclerosing fibrous lesions, given morphological similarities. PFP is a rare, intrascrotal benign fibrous mass of uncertain etiology. Given the lack of characteristic clinical signs or imaging findings, these masses can appear similar to a testicular neoplasm, leading to radical orchiectomy as opposed to a testis-sparing surgery. Frozen section assessment in testicular and paratesticular lesions may avoid unnecessary radical orchiectomy [10].

Urethra

IgG4 related pseudotumor has also been documented to occur in the urethra. Choi et al describe a case report of IgG4 related pseudotumor, in a patient who initially presented with lower urinary tract symptoms. Her past medical history was significant for eyelid inflammatory pseudotumor and pancreatitis over a decade prior. Urinalysis revealed hematuria and a firm urethral mass was discovered on cystoscopy. Core needle biopsy findings were consistent for an IgG4 pseudotumor. Pt underwent steroid therapy for several months, with marked improvement on follow up MRI [4].

As there is a paucity of research, information regarding recurrence rates is limited. It is important to keep in mind that prior medical history, including history of autoimmune pancreatitis or other inflammatory mass lesions, could suggest IgG4 related disease processes. In most cases, a needle biopsy under or intraoperative frozen sectioning can be helpful to establish a pathologic diagnosis prior to extirpative surgery. There are three key histopathologic findings of this disease: [1] dense lymphoplasmacytic infiltration, [2] storiform-type fibrosis, and [3] obliterative phlebitis [11]. If two of the three key histologic findings are present, the possibility of IgG4-related disease is strongly suggested pathologically. The most essential criterion to diagnose the disease is the detection of IgG4-positive plasma cells in the lesion [7].