Adult-onset multifocal retroperitoneal plexiform neurofibromas: a case report

Abstract

Background

Plexiform neurofibromas are benign peripheral nerve sheath tumors that typically present in childhood and are most often associated with neurofibromatosis type 1. They usually manifest as diffuse, infiltrative masses involving a single nerve distribution. Adult-onset, multifocal, discrete retroperitoneal plexiform neurofibromas are rare and sparsely reported. This case is presented to expand the known phenotypic spectrum and to emphasize the diagnostic challenges posed by atypical presentations.

Case presentation

A 37-year-old Iranian woman presented with a 3-month history of vague, intermittent abdominal pain without bowel or urinary symptoms. Her medical history was notable for long-standing refractory iron deficiency anemia of unknown cause. Physical examination revealed mild bilateral lower abdominal tenderness with no palpable masses or neurological deficits. Laboratory investigations confirmed microcytic anemia. Although anemia has occasionally been reported in patients with neurofibromatosis type 1 due to associated gastrointestinal lesions or chronic disease, no evidence of such an association was identified in our patient, and the anemia was considered an incidental comorbidity. Abdominal ultrasonography demonstrated bilateral hydronephrosis, prompting further imaging. Computed tomography revealed multiple well-defined soft tissue masses along the bilateral paraspinal and psoas muscles, causing ureteral compression. Magnetic resonance imaging showed lesions that were isointense to muscle on T1-weighted sequences and hyperintense on T2-weighted sequences, with persistent signal on fat-suppressed images and contrast enhancement. No osseous involvement or intra-abdominal organ invasion was identified. The imaging findings were highly suggestive of plexiform neurofibromas, and the diagnosis is therefore radiologically favored in the absence of histopathological confirmation. Genetic testing and further management were recommended; however, the patient did not return for follow-up.

Conclusions

This case illustrates an unusual adult-onset, multifocal, discrete presentation of plexiform neurofibromas in the retroperitoneum without a prior diagnosis of neurofibromatosis type 1. Recognition of such atypical imaging and clinical features is important to avoid misdiagnosis and unnecessary intervention. The case underscores the value of multimodality imaging in identifying rare variants and highlights the need for heightened clinical awareness of phenotypic variability in plexiform neurofibromas.

Background

Neurofibromas are benign peripheral nerve sheath tumors that arise from the peripheral nervous system [1]. These tumors have a predilection to develop in various locations throughout the body and are often seen in patients with neurofibromatosis type 1 (NF1), a genetic disorder characterized by abnormalities in the NF1 gene [2]. Neurofibromas are soft, fleshy growths that typically form on or under the skin, but can also occur within major or minor nerves, arising from Schwann cells that envelope nerve fibers. Plexiform neurofibroma is a distinct subtype characterized by diffuse, infiltrative growth involving multiple nerve fascicles and may present as a solitary or multifocal lesion [3]. Diagnosis is based on clinical examination and imaging. MRI is essential for determining tumor location, extent, and relationship to adjacent structures. Computed tomography (CT) and positron emission tomography (PET) can provide additional diagnostic information [4].

The clinical manifestations of plexiform neurofibroma can vary depending on factors such as tumor size, location and individual patient characteristics. Common presentations include multiple soft skin nodules, pain or numbness if nerves are compressed, and disfigurement in the case of plexiform neurofibromas [5]. It is important for clinicians to be aware of the various presentations of plexiform neurofibroma. Rare variants like plexiform neurofibromas can exhibit atypical clinical features that differ from classic NF1 manifestations [6]. Recognizing these uncommon histological and symptom patterns is vital for several reasons. First, unusual tumor characteristics may mimic malignant growths on initial examination, requiring accurate diagnosis to guide management and avoid unnecessary treatment. Second, identifying rare presentations enhances our understanding of the disease variability seen in NF1 and associated neurofibromatosis complications, which can range widely between patients. Third, knowledge of diverse clinical variants helps tailor personalized treatment approaches and monitoring plans, particularly for those at increased risk of malignant transformation [7]. In this report, we describe clinical and imaging features of a 37-year-old woman who presented with a rare multifocal variant of plexiform neurofibroma not commonly seen in clinical practice, emphasizing the importance of recognizing atypical disease manifestations. To our knowledge, adult-onset multifocal discrete retroperitoneal plexiform neurofibromas without an established NF1 diagnosis are rarely reported.

Case presentation

A 37-year-old female presented to our medical center with a 3-month history of vague abdominal pain. She described the pain as intermittent, non-radiating, and worsening over time. She reported no associated bowel or bladder symptoms. Her past medical history was significant for refractory iron deficiency anemia since teenage years of unknown etiology despite gastrointestinal workup. She had no other significant past surgical or medical illnesses. The patient's family history was non-contributory. A review of systems was otherwise unremarkable. On examination, her abdomen was soft but tenderness was elicited in the bilateral lower quadrants. No palpable masses or organomegaly were noted. Neurological exam was normal.

Initial laboratory investigations demonstrated microcytic anemia with iron studies consistent with anemia of chronic disease. The patient had a long-standing history of microcytic iron deficiency anemia of unclear etiology, which was noted as a relevant background clinical finding but was not established as being directly related to the retroperitoneal plexiform neurofibromas. An abdominal ultrasound examination ordered by her primary care physician revealed evidence of bilateral hydronephrosis. She was then referred to our department for further evaluation. The abdominal CT demonstrated well-circumscribed soft tissue masses along the paraspinal and psoas muscles bilaterally. The lesions varied in size from 1 to 3 cm in diameter. They appeared homogenously isoattenuating to muscle on non-contrast images. No areas of necrosis or calcification were noted. On contrast-enhanced images, the lesions demonstrated mild, homogeneous enhancement (Fig. 1) demonstrates conglomerated soft-tissue masses causing compression of both ureters with resultant bilateral hydronephrosis.

Fig. 1.

Contrast-enhanced axial computed tomography images of the abdomen demonstrating multiple, well-defined, homogenously enhancing soft-tissue masses along the bilateral paraspinal and psoas muscles. The lesions exert a mass effect on both ureters, resulting in bilateral hydronephrosis. No evidence of necrosis, calcification, or adjacent osseous involvement is identified

Corresponding axial T1-weighted MRI showed the lesions are isointense to muscle. On T2-weighted images, they demonstrated high signal intensity similar to fat. The lesions retained their high signal on fat-suppressed sequences, indicating they were not lipomatous. Following intravenous gadolinium administration, the lesions demonstrated enhancement. No involvement of the vertebral bones or infiltration into the abdomen was seen. Overall, the imaging findings were most consistent with plexiform neurofibromas (Fig. 2).

Fig. 2.

Magnetic resonance imaging of the abdomen demonstrates multiple well-defined retroperitoneal lesions along the bilateral paraspinal and psoas muscles. The lesions are isointense to skeletal muscle on T1-weighted images, hyperintense on T2-weighted images, and show persistent hyperintensity on fat-suppressed sequences with post-contrast enhancement, findings that are most consistent with plexiform neurofibromas. No osseous invasion or intra-abdominal organ involvement is identified

Given the clinical history of vague abdominal pain and imaging findings of multiple enhancing retroperitoneal lesions along the bilateral paraspinal and psoas muscles, a diagnosis of plexiform neurofibroma was strongly suspected. However, she did not follow up with our recommended genetic testing and management. Histopathological confirmation was not obtained due to the patient’s failure to attend follow-up. No definite intraspinal extension was identified on the available imaging.

Discussion and conclusions

Neurofibromatosis (NF) is a genetic disorder characterized by the development of multiple tumors called neurofibromas, which arise from nerve sheath cells. The most common form, NF1, also known as von Recklinghausen's disease, affects approximately 1 in 2,500 births and has nearly complete penetrance by age five [7, 8]. NF1 is inherited in an autosomal dominant pattern and is associated with various symptoms, including skin changes (such as café-au-lait spots), freckling in specific areas, and neurological complications [9]. Plexiform Neurofibroma is a specific type of neurofibroma that is particularly associated with NF1. Unlike typical neurofibromas, plexiform neurofibromas are irregular, infiltrative tumors that can involve multiple nerve fascicles and extend beyond the epineurium into surrounding tissues [8, 10]. They are often described as having a "bag of worms" appearance due to their diffuse nature. Plexiform neurofibromas can occur in approximately 30% of individuals with NF1 and may lead to significant morbidity due to their size and potential for malignant transformation [11].

The case presented here demonstrates an uncommon plexiform neurofibroma variant involving multiple discrete tumors along the paraspinal and psoas muscles bilaterally. While plexiform neurofibromas typically present early in life, often by the age of 6, the unusually late age at diagnosis at 37 years for this woman with abdominal signs reflects the variable onset that can occur, particularly in rarer subtypes. Her history of microcytic anemia predated the imaging diagnosis and was not proven to be directly related to the retroperitoneal lesions. Although anemia has been reported in patients with neurofibromatosis type 1, it is generally secondary to chronic disease, gastrointestinal bleeding from associated gastrointestinal stromal tumors or vascular abnormalities, nutritional deficiencies, or less commonly hematologic disorders, rather than the neurofibromas themselves. Our patient had no clinical, laboratory, or imaging findings suggesting these mechanisms. Therefore, we believe the microcytic anemia represents an unrelated comorbidity rather than a disease-specific feature of plexiform neurofibromas. Based on the available clinical information, the patient did not fulfill current diagnostic criteria for neurofibromatosis type 1 (NF1), as there was no documentation of café-au-lait macules, axillary or inguinal freckling, Lisch nodules, cutaneous neurofibromas, family history, or molecular confirmation.

Imaging plays a crucial role in the evaluation and management of plexiform neurofibromatosis. Magnetic resonance imaging (MRI) is considered the gold standard diagnostic tool given its high sensitivity and specificity for delineating soft tissue tumors. MRI can clearly define the infiltrative nature of plexiform neurofibromas and visualize characteristic features like the "target sign". This assists in differentiating plexiform neurofibromas from other lesions and determining the extent of disease [12]. Imaging is also vital for monitoring patients over time by assessing changes in tumor size, characteristics or identifying suspicious lesions that may indicate malignant transformation. In patients undergoing treatment, follow-up imaging allows evaluation of treatment response. Regular surveillance imaging helps detect complications early and guide clinical decision-making regarding surgery or conservative management [13, 14].

These tumors often present on CT imaging as large, lobulated soft tissue masses that appear hypoattenuating relative to surrounding muscles and fat. Internal characteristics such as multiple scattered spherical and tubular foci contribute to their heterogeneous appearance. A distinctive central region of lower attenuation surrounded by a higher attenuation rim, known as the "target sign", may also be seen [15]. Importantly, CT can demonstrate the infiltrative nature of these tumors and their involvement of multiple nerve branches as well as surrounding tissues. In addition, there is typically no evidence of bony invasion. Contrast-enhanced CT can provide supplementary information about vascularity. The delineation of tumor extent and relationship to surrounding structures afforded by CT imaging is crucial for surgical planning and monitoring potential changes that may indicate malignant transformation over time [16, 17].

On MRI, these tumors typically appear hypointense on T1-weighted sequences and hyperintense on T2-weighted imaging due to their high-water content and cellular composition. A characteristic "target sign" may be seen, consisting of a central area of high T2 signal intensity surrounded by low signal, reflecting the tumor's structure [18]. MRI clearly depicts the infiltrative growth pattern involving multiple nerve fascicles and surrounding tissues. Additionally, restricted diffusion on diffusion-weighted imaging (DWI) is common. Post-contrast sequences may demonstrate variable enhancement patterns. Importantly, MRI does not detect bone involvement. Together, these imaging characteristics aid in distinguishing plexiform neurofibromas from other lesions [12, 19–21].

Diagnosing plexiform neurofibromas poses several challenges, requiring careful correlation of clinical and imaging findings. The differential diagnosis of multifocal retroperitoneal soft tissue lesions includes schwannoma, malignant peripheral nerve sheath tumor, schwannomatosis, lymphoma, metastatic lymphadenopathy, desmoid tumor, soft tissue sarcoma, ganglioneuroma, and retroperitoneal fibrosis. Imaging characteristics, lesion distribution, enhancement pattern, and the absence of aggressive osseous invasion or widespread nodal disease help narrow the differential, but tissue diagnosis remains important when feasible [13]. Imaging may also underestimate tumor extent or exhibit variable characteristics between patients. The clinical context, including associated features of neurofibromatosis type 1 (NF1), provides valuable information to aid interpretation. Symptoms alone may not reliably distinguish plexiform neurofibromas from alternative conditions. In ambiguous cases, histological confirmation is sometimes needed when imaging suggests rapid growth or malignant transformation. While MRI is especially useful for characterizing plexiform neurofibromas, imaging findings alone are not always definitive for diagnosis, and histopathological confirmation remains the gold standard when clinically feasible [7, 22]. Careful consideration of patient history, examination, molecular markers and sometimes tissue sampling are important adjuncts that help overcome limitations and corroborate imaging to establish an accurate diagnosis [12]. Regular follow-up is also critical given complications like malignant degeneration. A multidisciplinary approach integrating comprehensive clinical and imaging data is therefore important for optimally diagnosing and managing these complex tumors. In this case, the bilateral paraspinal and psoas distribution with imaging features favoring peripheral nerve sheath origin made plexiform neurofibroma the leading diagnosis. In the present case, the diagnosis is therefore radiologically favored based on characteristic multimodality imaging findings and clinical correlation, but it should be interpreted with caution in the absence of tissue confirmation.

The strength of this case report lies in documenting a rare adult-onset, multifocal, discrete retroperitoneal presentation of plexiform neurofibromas, with detailed characterization using computed tomography and magnetic resonance imaging that enabled accurate noninvasive diagnosis and assessment of lesion extent and mass effect. Limitations include the absence of genetic testing for neurofibromatosis type 1, lack of histopathological confirmation, and unavailability of long-term follow-up due to loss to follow-up, which restricted evaluation of disease progression and malignant potential. The absence of histopathological confirmation is an important limitation of this report. Accordingly, the diagnosis should be regarded as radiologically favored rather than definitively proven. Current NF1 criteria could not be confirmed because the patient’s clinical evaluation was incomplete and genetic testing was not performed. Nevertheless, this case is clinically relevant as it highlights the importance of recognizing atypical imaging presentations to avoid misdiagnosis and unnecessary invasive interventions, and it reinforces the critical role of multimodality imaging in guiding diagnostic reasoning and management in adult patients without classic features of neurofibromatosis type 1.

We present an unusual case of multiple discrete plexiform neurofibromas involving the paraspinal and psoas muscles in a patient with no established NF1 diagnosis. While classic plexiform neurofibromas often appear as single diffuse tumors, this case demonstrated an atypical multifocal variant not commonly described. Imaging characteristics on CT and MRI correlated well with the histopathological features of plexiform neurofibroma. This case expands the known spectrum of clinical presentations for this condition and highlights the importance of recognizing diverse manifestations that may mimic other lesions. It also emphasizes the value of multimodality imaging in establishing accurate diagnoses, particularly for rare variants that exhibit non-typical features. Correlating radiological findings with the clinical picture can help overcome limitations and avoid diagnostic pitfalls. Overall, this report enhances understanding of phenotypic variability in NF1 and associated tumor subtypes. It underscores the need for a high index of suspicion to avoid missed or delayed diagnoses. Regular surveillance imaging also allows early detection of complications and monitoring for malignant transformation.

Abbreviations

CT

Computed tomography

MRI

Magnetic resonance imaging

NF1

Neurofibromatosis type 1

PET

Positron emission tomography

MPNST

Malignant peripheral nerve sheath tumor

Author contributions

All authors contributed to data collection, literature review, interpretation of imaging findings, and manuscript preparation. All authors read and approved the final manuscript.

Funding

This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Ethical approval was not required for this single anonymized case report, as no identifiable patient information is presented.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare no competing interests.