Multifocal extrathoracic lymphadenopathy mimicking lymphoma: an atypical presentation of sarcoidosis without thoracic involvement

Abstract

Sarcoidosis is a systemic granulomatous disease of unknown etiology, typically affecting the lungs and bilateral hilar or mediastinal lymph nodes. We present a rare case of sarcoidosis in a 42-year-old woman with extensive lymphadenopathy involving cervical, axillary, retrocrural, peritoneal, retroperitoneal, and iliac regions, without pulmonary or mediastinal involvement, thereby radiologically simulating lymphoma. Histopathological evaluation revealed noncaseating granulomatous inflammation without evidence of malignancy or infection. This case highlights the diagnostic challenge posed by extrapulmonary sarcoidosis and underscores the critical role of biopsy in differentiating it from lymphoproliferative disorders. A high index of suspicion is essential when sarcoidosis presents without its classic thoracic features.

Introduction

Sarcoidosis is a multisystem inflammatory disorder characterized by noncaseating epithelioid granulomas, most commonly affecting adults aged 20–40 years. Its etiology remains unclear, although it is believed to involve an exaggerated immune response to unidentified antigens in genetically predisposed individuals [1,2]. The classic presentation, observed in over 90% of cases, involves bilateral hilar lymphadenopathy and parenchymal lung involvement [3].

However, isolated or multifocal extrapulmonary sarcoidosis without thoracic findings is uncommon and often mimics malignancy [4,5]. This report presents a rare case of sarcoidosis manifesting as widespread lymphadenopathy without pulmonary or mediastinal involvement, which radiologically simulated lymphoma. The absence of respiratory symptoms and normal pulmonary imaging complicated the diagnosis, which was ultimately confirmed through histopathology.

Case presentation

A 42-year-old woman with no significant past medical history presented with a 2-month history of progressive, painless swelling in the cervical and axillary regions, accompanied by mild fatigue and intermittent low-grade fever. She denied weight loss, night sweats, cough, dyspnea, or skin lesions.

Physical examination: Palpable, nontender, mobile lymph nodes were noted in the cervical and bilateral axillary regions. No hepatosplenomegaly was detected. There were no signs of cutaneous nodules or uveitis.

Laboratory investigations:

• •CBC, renal, and liver function tests: within normal limits
• •Serum ACE: 35 U/L (normal)
• •Serum calcium: 9.6 mg/dL (normal)
• •ESR: 48 mm/h; CRP: 12 mg/L
• •Serologies for HIV, EBV, CMV, and tuberculosis (Quantiferon-TB Gold): negative

Imaging studies:

• •Neck ultrasound: Revealed multiple oval, hypoechoic lymph nodes with loss of central hila in bilateral cervical chains.
• •
  Contrast-enhanced CT (CECT): Neck, chest, abdomen, and pelvis imaging showed:

  • ○
    Bilateral cervical (Fig. 1) and axillary (Fig. 2) lymphadenopathy
  • ○
    Retrocrural, retroperitoneal, peritoneal, and bilateral iliac lymphadenopathy (Fig. 4 and 5, Fig. 4 and 5)
  • ○
    No mediastinal or hilar lymphadenopathy (Fig. 2)
  • ○
    No pulmonary lesions, consolidations, or interstitial changes (Fig. 3)
  • ○
    Homogeneous, well-circumscribed, non-necrotic lymph nodes

Fig. 1.

Coronal CECT of the neck showing bilateral cervical lymphadenopathy, with homogeneous enhancement. No adjacent soft tissue invasion or necrosis. (White arrows).

Fig. 2.

Coronal CECT of the chest demonstrating bilateral axillary lymphadenopathy (white arrows), with absence of mediastinal and hilar lymph nodes.

Fig. 4 and 5.

Coronal and axial CECT of the abdomen and pelvis showing multiple enlarged retroperitoneal, peritoneal, and iliac lymph nodes (white arrows), as well as retro crural lymph nodes (black arrows). All of which are well-circumscribed and non-necrotic.

Fig. 3.

Coronal CECT of the chest (pulmonary window) showing clear lung fields, with no evidence of interstitial thickening, nodularity, or consolidation.

Given the extensive multiregional distribution of lymphadenopathy and the absence of infection, lymphoma, particularly non-Hodgkin’s lymphoma (NHL), was the primary imaging differential [6].

Biopsy and histopathology: An ultrasound-guided core needle biopsy of a right cervical lymph node was performed. Histologic examination revealed multiple, well-formed noncaseating granulomas composed of epithelioid histiocytes and multinucleated giant cells (Fig. 6). There was no necrosis, malignancy, or Reed–Sternberg cells. Special stains for mycobacteria (Ziehl-Neelsen), fungi (PAS, GMS) were negative, confirming a diagnosis of sarcoidosis.

Fig. 6.

Histopathology (H&E, 40×) of the axillary lymph node biopsy showing multiple noncaseating epithelioid granulomas, composed of Langhans-type multinucleated giant cells and epithelioid histiocytes. No evidence of necrosis or malignancy.

Discussion

Sarcoidosis is a systemic granulomatous disease of unknown etiology, typically presenting with intrathoracic lymphadenopathy, parenchymal lung involvement, or both. Over 90% of patients exhibit thoracic manifestations, making these findings key diagnostic anchors in clinical and imaging assessments [3]. However, in a small subset of patients, sarcoidosis may present with extrapulmonary findings alone—most commonly involving the skin, eyes, or peripheral lymph nodes [5]. When lymphadenopathy is extensive and thoracic findings are absent, the radiologic appearance may closely mimic lymphoma, posing a significant diagnostic dilemma [6].

The present case exemplifies this rare and diagnostically challenging presentation. The patient had widespread lymphadenopathy—cervical, axillary, retroperitoneal, retrocrural, peritoneal, and iliac—without any hilar or mediastinal adenopathy and without lung parenchymal involvement on high-resolution CT. This constellation is more characteristic of low-grade non-Hodgkin lymphoma, particularly given the systemic nodal distribution and absence of systemic infectious symptoms [6,7]. In such a context, the radiologic pattern aligns poorly with typical sarcoidosis and is more consistent with lymphoproliferative disease.

Imaging findings alone, however, are insufficient to reliably differentiate sarcoidosis from lymphoma. In this case, the lymph nodes were homogeneous, non-necrotic, and well-marginated—features seen in both diseases [6,8]. The absence of necrosis or matted nodes made tuberculosis and fungal lymphadenitis less likely, though not excludable without histopathology. In sarcoidosis, lymph nodes may enhance homogeneously and be found in deep and peripheral nodal stations, but such a widespread distribution without thoracic involvement is highly atypical [3,4]. Additionally, the lack of hypermetabolism data (e.g., from PET-CT) further limited noninvasive characterization.

Given this diagnostic ambiguity, histopathologic analysis is essential. The biopsy in our patient revealed well-formed noncaseating granulomas, which are the histologic hallmark of sarcoidosis [2,9]. The absence of necrosis, neoplastic infiltration, and infectious organisms (confirmed by negative Ziehl-Neelsen and PAS staining) supported the diagnosis. However, it is important to note that noncaseating granulomas are not pathognomonic for sarcoidosis and can be seen in a variety of conditions, including sarcoid-like reactions associated with malignancies, particularly Hodgkin lymphoma and certain carcinomas [10]. Hence, careful correlation with the overall clinical and imaging picture—and exclusion of other causes—is crucial.

Interestingly, in our case, serum ACE levels and calcium were within normal limits, a finding that may seem contradictory given their common association with active sarcoidosis. However, these markers have limited sensitivity and specificity. ACE levels are elevated in only 60%-70% of active cases and are particularly unreliable in extrapulmonary or limited disease [3]. Normocalcemia is also not uncommon, especially in patients lacking significant granulomatous activity in organs like the lung, liver, or bone marrow.

From a diagnostic workflow perspective, this case reinforces the limitations of imaging in distinguishing granulomatous from neoplastic lymphadenopathy and emphasizes the need for tissue diagnosis in all cases of unexplained systemic lymphadenopathy. While radiology can strongly suggest a diagnosis, particularly when patterns are classic (eg, perilymphatic nodules with bilateral hilar adenopathy in sarcoidosis), atypical presentations such as this warrant histologic confirmation [6,8].

Furthermore, this case expands the spectrum of sarcoidosis presentations by illustrating that multiregional lymphadenopathy can occur without any thoracic involvement, albeit rarely. Similar cases have been documented, but they remain exceptional and easily mistaken for malignancy without biopsy [9]. Clinicians and radiologists should, therefore, remain vigilant and include sarcoidosis in the differential diagnosis—even when classic thoracic signs are absent—especially when histology or negative infectious workup points toward a granulomatous etiology.

Conclusion

This case illustrates a rare presentation of sarcoidosis mimicking lymphoma, with multifocal extrapulmonary lymphadenopathy and no thoracic involvement. In such scenarios, radiologic features alone are insufficient for diagnosis, and histopathological confirmation is essential. Clinicians and radiologists must consider sarcoidosis—even in the absence of pulmonary or mediastinal findings—when evaluating systemic lymphadenopathy to avoid misdiagnosis and unnecessary oncologic treatment.

Patient consent

Written informed consent was obtained from the patient for the publication of this case report and accompanying images.