An Unusual Case of High-Grade Non-Hodgkin Lymphoma Masquerading as Acute Pyelonephritis with Acute Kidney Injury

Introduction

Renal involvement in non-Hodgkin lymphoma (NHL) has been reported to present with glomerulonephritis, acute kidney injury (AKI), and lymphoma infiltrating the kidney parenchyma.[1] We discuss an unusual case who presented with acute pyelonephritis (leucocytosis and acute kidney injury), ovarian mass, and compressive myelopathy and was finally diagnosed as NHL.

Case Report

A 43-year-old married female was admitted to our hospital with history of fever, right side flank pain, and burning micturition. Fever subsided in a week after symptomatic medication. Pain was both in flank and lower back region, used to get relieved with medication, non-radiating, not associated with aggravating factors. There was no history of weight loss, night sweats, anorexia. She had been recently diagnosed with type 2 diabetes mellitus and hypertension and was on insulin during hospital stay and amlodipine; but fundus examination was not suggestive of diabetic retinopathy. General examination; pulse rate- 88/min, BP- 130/90 mmHg. On systemic examination she had right side renal angle tenderness.

Laboratory examination showed; TLC of 57,000 with polymorphs of 80%, urine routine suggestive of protein of 1+, RBC 3-5 and pus cells 5-8 per high power field, blood urea 60 mg/dl, creatinine 3.2 mg/dl, 24 h urinary protein 1,600 mg/day. Ultrasonography was suggestive of normal sized kidneys, with left adnexal hypoechoic cyst of size 5.4 × 4.8 cm with internal echoes suggestive of hemorrhagic ovarian cyst. Her urine and blood cultures were sterile and procalcitonin level was less than 0.5 ng/ml. Initially she was diagnosed as acute pyelonephritis (APN) and managed with intravenous antibiotics. In view of persistent leucocytosis even after treatment with antibiotics, to rule out leukemoid reaction and to look for the infiltration of lymphoma, bone marrow aspiration and biopsy was done, which was suggestive of reactive marrow with myeloid hyperplasia., Few marrow spaces showed focal areas of likely early fibrosis (grade 1 on Reticulin stain).

Serum tumor markers were within normal limits with slightly elevated CA125. Ultrasound with doppler didn't show any evidence of ovarian torsion. Contrast enhanced CT chest and abdomen revealed heterogeneously enhancing solid mass measuring 6.5 × 4.8 × 4.8 cm in pelvis likely arising from left ovary [Figure 1a]. In view of acute persistent pain, she underwent right side salpingoophorectomy [Figure 1b]. After the operation her pain abdomen reduced.

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Figure 1

(a) CECT abdomen suggestive of heterogeneously enhancing solid mass measuring 6.5 × 4.8 × 4.8 cm in pelvis arising from left ovary. (b) gross specimen of left ovary measuring 6 × 5 × 3 cm showing enlarged ovary with attached fallopian tube. (c) ovarian mass histology showing atypical cells which are highly pleomorphic and show hyperchromatic nucleus with coarse chromatin. (d) long segment infiltrating lesion in right epidural space extending from D4 to D10 vertebral level. (e) renal histology showing normal glomerulus. (f and g) PET CT showing increased uptake in bone marrow

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Histopathology of the ovarian mass showed fibrocollagenous tissue infiltrated by singly lined atypical cells predominantly arranged in sheets and focally in loose nests and alveolar pattern [Figure 1c]. The tumor cells were highly pleomorphic and showed hyperchromatic nucleus with coarse chromatin. Brisk mitotic activity was seen. Native ovarian parenchyma was not identified in the multiple sections examined. Sections from the fallopian tube showed infiltration of the mucosa by similar tumor cells. Large panel of immunohistochemistry markers including PLAP, AFP, EMA, Cytokeratin, ER, PR, Inhibin, S100, SMA, Desmin, Vimentin, CD99, and synaptophysin were negative. It was followed by lymphoma panel including CD20, CD79a, CD45RO, CD3, CD34, CD 30, CD43, and Cd68. Tumor cells were positive for LCA and CD43 while CD 68 showed focal positivity. Rest of the markers were negative. A diagnosis of hematolymphoid malignancy was made. Another IHC panel applied for further characterization of malignant cells included CD117, Tdt, MPO, CD56, CD4, and CD8 turned out to be negative. High grade NHL, unclassified probably monocytic leukemic infiltration was the final diagnosis.

During hospital stay she developed bilateral lower limb weakness and urinary retention and on examination had sensory level at D10 vertebra. As per the neurologist's opinion she underwent MRI dorso-lumbar spine which was suggestive of long segment infiltrating lesion in right epidural space extending from D4 to D10 vertebral level [Figure 1d].

In view of proteinuria and renal dysfunction she underwent renal biopsy which had 15 glomeruli that were largely unremarkable [Figure 1e]. Tubules showed acute tubular injury. Tubular atrophy and interstitial fibrosis involved about 20–30% of sampled cortex. Focal moderate to dense interstitial inflammation was noted comprising lymphocytes with few neutrophils. Direct immunoflourescence studies for IgG, IgA, IgM, C3, C1q, kappa and lambda were negative. Therefore, the renal biopsy impression kept was acute tubulointerstitial nephritis. 18FDG-PET/CT demonstrated bone marrow involvement characterized by a high 18FDG uptake [Figure 1f, g]. She has been offered treatment with CHOP plus rituximab regimen.but the family opted for alternative therapy.

Discussion

Pyelonephritis typically manifests with signs and symptoms of both systemic inflammation (e.g., fever, chills, and malaise) and bladder inflammation (e.g., urinary frequency, urgency, and dysuria). Bacterial pyelonephritis may be associated with acute kidney injury, particularly when the clinical presentation includes hypotension, obstruction to the flow of urine, and the use of nephrotoxic drugs or contrast agent. When it occurs in patients without obvious predisposing causes, the possibility of bacterial pyelonephritis is often not considered, and such cases may present diagnostic dilemmas. Similarly our case made us to look for other cause.[2]

Kidney involvement is an under-recognized complication of NHL. The diversity of lymphoma-related renal manifestations makes diagnosis difficult. While abrupt worsening of kidney function may be thefirst sign of malignant disease. Kidney manifestations encompass a broad spectrum of disease: prerenal acute kidney injury (AKI), acute tubular necrosis (ATN), renovascular disease, parenchymal infiltration, obstruction, glomerulopathies, and electrolyte and acid-base abnormalities.[1]

Glomerulopathies in NHL occur earlier and progress with disease. Proliferative lesions may account for up to 30% of glomerular diseases. However, in our case it is tubulointerstitial nephritis and acute tubular injury. It has been hypothesized that cytokines produced by lymphoma cells may cause tubular injury and interstitial fibrosis. Another explanation for kidney dysfunction is an elevated pressure in renal parenchyma caused by lymphocytic infiltration leading to compression of tubules and modifications in microvascular structure. Malignant lymphoid cells may occur in the ovary either as a primary neoplasm or as a secondary manifestation of a disseminated occult or known disease.[3] Only 1% of patients further diagnosed with malignant lymphoma present initially with ovarian enlargement.[4] Primary ovarian lymphoma, account for 0.5% of all NHL and 1.5% of all ovarian neoplasms.

CD45, CD20, CD79a are selective marker that recognizes a subpopulation of B-cells, CD3, CD 45RO, CD43 is the marker for T-cells and NK-cells, CD30 is the marker for activated T-cells and B-cells. Human leukocyte common antigen (LCA) is identified on B and t lymphocytes. CD45 immunoreactivity is recognized to be highly specific for NHLs. Markers of myeloid cells and monocytes are anti-myeloperoxidase, CD34, CD68, CD43.[5]

Lymphomas of the ovary can occur at any age, but most often in women over the age of 40.[6] The most common presenting signs or symptoms of malignant lymphomas involving the ovaries are abdominal or pelvic pain or mass. Fever, night sweats, fatigue, or weight loss (B symptoms) was noted in 10–33% of the patients. B- and T-cell NHL can arise in the ovary, but B-cell tumors are much more frequent. Both B- and T-cell NHL can arise in the ovary, but B-cell tumors are much more frequent. The histological differential diagnosis includes granulosa cell tumor, dysgerminoma, small-cell carcinoma of hypercalcemic type, granulocytic sarcoma, and poorly differentiated surface-epithelial or metastatic carcinoma.[7]

Our patient had leukocytosis for which no relevant explanation is found in literature. However, it is seen that leukocytosis or leukemoid reaction may develop in association with carcinomas of the lung and stomach.[8] Previous reports in literature similar to our case are mentioned in Table 1.

Conclusion

This is an unusual case of NHL without bone marrow involvement presenting as ovarian mass, persistent leukocytosis, renal dysfunction mimicking acute pyelonephritis and paraparesis symptomatically improved after treatment.