軟化斑與多發性骨髓瘤-罕見病例報告

柯旭承¹、賴韋宏¹、周詠欽^1,2

¹戴德森醫療財團法人嘉義基督教醫院 外科部 泌尿科

²亞洲大學 食品營養與保健生技學系

Malakoplakia in a Patient with Multiple Myeloma – A Rare Case Report

Hsu-Cheng Ko¹, Wei-Hong Lai¹, Yeong-Chin Jou^1,2

¹Department of Urology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan

²Department of Health and Nutrition Biotechnology, Asian University, Taichung

Introduction:

Malakoplakia is an inflammatory condition characterized by decreased phagocytic function of macrophages and usually affects patients with underlying immunosuppression. Although commonly associated with immunosuppression, malakoplakia has only rarely been reported in association with hematologic malignancies. Herein, we reported a case of multiple myeloma (MM), who later received chemotherapy regimens and autologous peripheral blood stem cell transplant in one year. Recurrent urinary tract infection complicated with right hydronephrosis because of malakoplakia developed six years after treatment course of multiple myeloma.

Case presentation:

The 70-year-old female was a case of multiple myeloma status post chemotherapy treatment and autologous peripheral blood stem cell transplant (auto-PBSCT) in 2014. In September 2021, she suffered from dysuria and frequency when micturition and visited the Urology Department. The urine was cloudy in appearance, and it contained leukocytes esterase, more than 100 white blood cells and 19 red blood cells. Urine culture grew Escherichia coli and Klebsiella pneumoniae. We prescribed antibiotics suggested by sensitivity test. Her symptoms improved a lot. Four months later, right hydronephrosis was accidentally found on renal sonograph. Serum creatinine level increased from baseline 2 mg/dL to 6.88 mg/dL. Non-enhanced abdominal computed tomography showed right hydroureter, right hydronephrosis, wall thickening of urinary bladder (UB) and multiple protruding tumors into UB cavity. She then underwent cystoscope and flexible ureterorenoscope (URS). Multiple nodular tumors over whole UB and right ureteral orifice obstructed by lesions were found. Resection of bladder tumors was performed smoothly. We then passed URS along right ureter and into right renal pelvis. No nodular lesion was found.  Right double-J catheter was inserted before the end of operation. The specimen was sent for pathology confirming the diagnosis of UB malakoplakia. Double-J catheter was removed two week later. Level of serum creatinine returned to baseline. Right hydronephrosis also decreased in severity.

Discussion:

Malakoplakia is a rare chronic granulomatous response to infective agents in immunosuppressive individuals and mostly affects genitourinary tract. It reveals itself as recurrent urinary tract infection. In some cases, renal impairment is one of clinical presentations of malakoplakia.  It also has been described in other organs, such as lung, parotid gland, colon, and skin. Majority of patients are either on a treatment of immunosuppressive agents (i.e. steroids, immunomodulatory agents, chemotherapy)

or suffering from a disease (status post organ transplant, cancer requiring chemotherapy) that compromises their immunity.

Immunity plays a critical role in pathophysiology of malakoplakia. Studies have suggested that a decrease of intracellular cyclic guanosine monophosphate (cGMP) in macrophage or monocyte interferes with microtubular function, lysosomal activity, and stimulus of tumor necrosis factor. The deficit leads to declined degradation of lysosomes and inability to release their enzymes. Macrophage or monocyte with decreased phagocytic function could not remove bacteria completely. Partially digested bacteria accumulate intracellularly and result in deposition of iron and calcium on bacterial glycolipid.

Diagnosis of malakoplakia is mainly based on histological findings. The specimen contains aggregates of histiocytes (collections of histiocytes with granular eosinophilic cytoplasm known as von Hanseman cells), neutrophils, lymphocyte, plasma cells, basophilic Michaelis-Gutmann body, granulation tissue and deposit of iron and calcium.

Macrophages constitute heterogeneous population deriving from blood monocytes, that are able to display different functional activities; for instance, they can be immunostimulatory or immunosuppressive. Heterogeneity of macrophage has been simplified in cell polarization concept that discriminates macrophages into different types, schematically identified as M1 (activation of immune response) and M2 (poor antigen-presenting capability and wound-healing promotion). Regarding macrophage polarization, environmental signals play an important role. It is conceivable that once recruited to the multiple myeloma microenvironment, monocytes are exposed to tumor- and stroma-secreted factors (such as IL-10, hypoxia) and may acquire characteristics of M2 polarization. M2 macrophages further lead to tumor progression, tumor cell proliferation, angiogenesis and immunosuppressive microenvironment.

Although commonly associated with immunosuppression, malakoplakia has only rarely been reported in association with hematologic malignancies. Siraj M El Jamal et al reported an extragenitourinary malakoplakia in a patient with myeloma. However, in that article, the authors did not illustrate the possible association between malakoplakia and multiple myeloma. The theory of reducing intracellular cGMP in macrophages leading to malakoplakia formation was first introduced in 1977. From the view of multiple myeloma, the M2 polarization and intercellular signaling pathway also seem to play important role in formation of malakoplakia. However, the exact association between malakoplakia and multiple myeloma has not yet been proposed. It takes more studies to investigate the underlying pathological mechanisms.

Conclusions:

Recurrent urinary tract infection is a common clinical presentation in patients with compromised immunity. Although urinary tract infection might deteriorate renal function, clinician should also pay attention to anatomical obstruction along genitourinary tract. In this case report, we also present possible molecular pathophysiology of malakoplakia from the view of multiple myeloma aside from a decrease of intracellular cyclic guanosine monophosphate.