Differential Tracer Uptake on FDG PET/CT Unmasking Dual Pathology - Systemic Amyloidosis with Active Tuberculosis

INTRODUCTION

Amyloidosis comprises a heterogeneous group of disorders characterised by extracellular deposition of insoluble fibrillar proteins arranged in a β-pleated sheet configuration, leading to progressive organ dysfunction.^[1,2] Depending on the precursor protein, amyloidosis is classified into several types, including AL (light-chain), AA (secondary), ATTR, and others. Systemic amyloidosis often presents with nonspecific symptoms such as fatigue, weight loss, enema, or organ-specific manifestations, making early diagnosis challenging.

While amyloid deposits are typically metabolically inactive or show low-grade fluorodeoxyglucose (FDG) uptake, inflammatory and infectious processes such as tuberculosis (TB) demonstrate intense FDG avidity due to increased glucose metabolism in activated inflammatory cells.^[3,4] In TB-endemic regions, FDG-avid lymphadenopathy often poses a diagnostic dilemma, particularly in patients with coexisting systemic diseases.

We describe a unique case in which FDG positron emission tomography–computed tomography (PET/CT) played a pivotal role in identifying two distinct pathological processes - diffuse systemic amyloidosis and metabolically active tuberculous lymphadenitis, based on differential tracer uptake and distribution, subsequently confirmed on histopathology.

CASE REPORT

A 58-year-old female presented with progressive abdominal discomfort and severe abdominal distension of several months’ duration. There was no significant history of fever, night sweats, or weight loss. Routine laboratory evaluation revealed normal renal function with a serum creatinine level of 0.48 mg/dL. Other biochemical parameters were unremarkable. In view of unexplained abdominal distension and suspected systemic pathology, a whole-body FDG PET/CT scan was advised for further evaluation.

Whole-body PET/CT imaging from vertex to feet was performed on a Siemens Biograph Horizon time-of-flight PET/CT scanner following intravenous administration of 10 mCi (370 MBq) of ¹⁸F FDG, under standard patient preparation and imaging protocols. Blood glucose levels were within normal limits prior to tracer injection. Fig 1 shows the PET/CT images. (A) Maximum intensity projection (MIP). (B and C) Fused coronal and sagittal views. (D and E) Trans axial fused PET/CT images revealed mildly FDG-avid (SUVmax ~1.1) diffuse soft tissue occupying almost the entire abdominopelvic cavity, similarly diffuse soft-tissue infiltration noted in the subcutaneous planes involving bilateral upper limbs, bilateral breast parenchyma, bilateral axillary regions, posterior thoracic wall, abdominal wall, bilateral gluteal regions, and bilateral lower limbs. (F and G) These infiltrates demonstrated multiple punctate and coarse calcifications on CT, suggesting a relatively metabolically inert process. (H and I) In contrast, a few intensely FDG-avid lymph nodes were identified, including right level II cervical and right supraclavicular (measures 2.6 × 2.3 cm; SUVmax 9.1) lymph nodes.

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Fig 1: Shows the fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) images. (A) Maximum intensity projection (MIP). (B and C) Fused coronal and sagittal views. (D and E) Trans axial fused PET/CT images revealed mildly FDG-avid (SUVmax ~1.1) diffuse soft tissue occupying almost the entire abdominopelvic cavity, similarly diffuse soft-tissue infiltration noted in the subcutaneous planes involving bilateral upper limbs, bilateral breast parenchyma, bilateral axillary regions, posterior thoracic wall, abdominal wall, bilateral gluteal regions, and bilateral lower limbs. (F and G) These infiltrates demonstrated multiple punctate and coarse calcifications on CT, suggesting a relatively metabolically inert process. (H and I) In contrast, a few intensely FDG-avid lymph nodes were identified, including right level II cervical and right supraclavicular (measures 2.6 × 2.3 cm; SUVmax 9.1) lymph nodes. The marked difference in FDG uptake between the intensely avid supraclavicular lymph nodes and the diffusely infiltrative, minimally avid soft-tissue deposits raised the possibility of dual pathology. SUVmax: Maximum standardised uptake value

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The marked difference in FDG uptake between the intensely avid lymph nodes and the diffusely infiltrative, minimally avid soft-tissue deposits raised the possibility of dual pathology and in Fig 2 histopathological findings are shown; (A) Biopsy (40x magnification) from the diffuse retroperitoneal soft-tissue infiltration showed shows extensive amyloid deposition in the blood vessel wall (arrow) and adipose tissue, along with scattered lymphoplasmacytic inflammatory infiltrate. (B and C) Congo red staining (100x) highlighted the deposits with characteristic apple-green birefringence under polarised light (400x), confirming amyloidosis. Immunohistochemistry demonstrated significantly higher expression of lambda light chains compared to kappa light chains, while amyloid A and β-amyloid were negative, favouring AL (light-chain) amyloidosis. There was no evidence of increased plasma cells, skeinoid fibrosis, or neoplastic pathology. Pancytokeratin, β-catenin, calretinin, CDK4, and MDM2 were negative, excluding epithelial, desmoid-type fibromatosis, and dedifferentiated liposarcoma. Smooth muscle actin highlighted fibromuscular tissue only. (D) Ultrasound guided Biopsy (100x) from the right supraclavicular lymph node revealed lymph-node parenchyma with numerous necrotizing epithelioid cell granulomas and Langhans giant cells. Ziehl–Neelsen staining for acid-fast bacilli was negative; however, the overall histomorphology was consistent with necrotizing granulomatous lymphadenitis favouring tuberculosis.

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Fig 2: Shows histopathological findings. (A) Biopsy (Congo red, 40x magnification) from the diffuse retroperitoneal soft-tissue infiltration showed shows extensive amyloid deposition in the blood vessel wall (arrow). (B and C) Congo red staining (100x) highlighted the deposits with characteristic apple-green birefringence under polarised light (400x), confirming amyloidosis. (D) Biopsy (Congo red, 100x) from the right supraclavicular lymph node revealed necrotising epithelioid cell granulomas.

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The marked difference in FDG uptake between the intensely avid lymph nodes and the diffusely infiltrative, minimally avid soft-tissue deposits raised the possibility of dual pathology.

Based on the combined imaging and histopathological findings, a diagnosis of concurrent systemic amyloidosis with active tuberculous lymphadenitis was established.

DISCUSSION

The coexistence of systemic amyloidosis and tuberculosis is rare but biologically plausible, particularly in regions where chronic infections remain prevalent.^[2,4] Chronic inflammatory conditions are classically associated with AA amyloidosis; however, in the present case, immunohistochemistry confirmed AL-type amyloidosis, indicating a separate plasma-cell dyscrasia–related process coexisting with active TB. FDG PET/CT plays a crucial role in such complex clinical scenarios by providing whole-body metabolic and anatomical assessment.^[3-5] Tuberculous lesions typically show intense FDG uptake due to activated macrophages and lymphocytes, often mimicking malignancy, whereas amyloid deposits generally demonstrate absent or low-grade FDG uptake reflecting their acellular and metabolically inert nature.^[4-6] Other differentials for low FDG avidity infiltrative disorders include sarcoidosis (fibrotic phase), IgG4-related disease, low-grade lymphomas (such as follicular, marginal zone or small lymphocytic lymphoma), other malignancies such as invasive lobular breast carcinoma, mucinous adenocarcinoma or diffuse gastric cancer (lienitis plastic). The presence of punctate and coarse calcifications within diffuse soft-tissue deposits is consistent with dystrophic calcification, which occurs in damaged or necrotic tissues despite normal serum calcium and phosphate levels. Dystrophic calcification is commonly associated with chronic inflammation, granulomatous diseases such as TB, and proteinaceous deposits, including amyloid.^[1-6] Malignant neoplasms such as mucinous adenocarcinomas, papillary carcinomas, treated lymphomas, and certain sarcomas may demonstrate dystrophic calcification due to tumour necrosis or degenerative changes, whereas benign tumours, including fibrous tumours and haemangiomas, may calcify over time.^[6,7]

In the present case, the striking disparity in FDG uptake between intensely FDG-avid lymph nodes (SUVmax 9.1) and diffusely infiltrative soft-tissue deposits with negligible metabolic activity (SUVmax ~1.1) served as a key imaging clue suggesting dual pathology rather than a single disseminated disease process. Recent literature emphasises the expanding role of FDG PET/CT in differentiating active infection from indolent infiltrative disorders, guiding biopsy, and preventing misdiagnosis, particularly in TB-endemic regions.^[7-10]

CONCLUSION

This case highlights the complementary role of FDG PET/CT in identifying and characterising coexisting infectious and infiltrative pathologies based on differential metabolic behaviour. Recognition of discordant FDG uptake patterns, especially in TB-endemic regions, is essential for accurate diagnosis and appropriate management. Histopathological confirmation remains indispensable, with FDG PET/CT serving as a valuable tool for guiding targeted biopsy and avoiding diagnostic pitfalls.