Delayed Uptake on ¹²³I‐IMP SPECT as a Diagnostic Clue in Cranial Vault Lymphoma in a 25‐Year‐Old Man: A Case Report

ABSTRACT

Lymphoma involving the cranial vault is an extremely rare condition that is often difficult to diagnose preoperatively because its imaging findings mimic those of other skull tumors. We report a case of diffuse large B‐cell lymphoma of the cranial vault in a 25‐year‐old man presenting with a rapidly enlarging frontal mass. Magnetic resonance imaging demonstrated marked diffusion‐weighted hyperintensity, and ¹²³I‐IMP SPECT showed increased tracer uptake with further accumulation on delayed images. These findings raised suspicion of malignant lymphoma before surgery. Histopathological examination confirmed diffuse large B‐cell lymphoma. This case suggests that ¹²³I‐IMP SPECT may provide useful adjunctive information for raising suspicion of lymphoma among cranial vault tumors and may contribute to improved preoperative diagnosis.

Key Clinical Message.

In cranial vault tumors, marked ¹²³I‐IMP uptake with increased retention on delayed SPECT images, combined with diffusion restriction on MRI, may provide an adjunctive imaging clue for suspecting malignant lymphoma preoperatively and facilitate appropriate diagnostic and therapeutic planning.

1. Introduction

Malignant lymphoma involving the cranial vault is a rare manifestation of extranodal non‐Hodgkin lymphoma [1, 2, 3, 4, 5, 6, 7, 8]. A systematic review of 111 reported cases of cranial vault lymphoma showed a mean patient age of 52 years, with a nearly equal sex distribution, and an enlarging subcutaneous scalp mass was the most common presenting symptom. Most reported cases were of B‐cell origin, with diffuse large B‐cell lymphoma (DLBCL) being the most common histological subtype [6]. Because its imaging findings often resemble those of other skull tumors such as meningioma or metastatic lesions, accurate preoperative diagnosis is challenging [3, 6, 7, 8]. Functional imaging modalities may provide additional diagnostic information; however, the usefulness of N‐isopropyl‐p‐[¹²³I]iodoamphetamine single‐photon emission computed tomography (¹²³I‐IMP SPECT) in cranial vault lymphoma has rarely been reported [9, 10]. Here, we report a case of cranial vault DLBCL in a 25‐year‐old man and discuss the potential role of ¹²³I‐IMP SPECT as an adjunctive imaging modality for the preoperative diagnosis of cranial vault lymphoma.

2. Case History/Examination

A 25‐year‐old Japanese man with no significant medical history presented with a progressively enlarging frontal mass. Three months before presentation to our hospital, he had experienced transient weakness of the left lower extremity. Two months before presentation, he noticed a mass in the midline frontal region, which gradually enlarged toward the left side. He visited a local hospital because of progressive enlargement of the mass. Magnetic resonance imaging (MRI) revealed a skull tumor, and he was subsequently referred to our department for further evaluation. Neurological examination on admission revealed no focal neurological deficits. Follow‐up imaging performed 2 weeks later demonstrated further enlargement of the tumor. He reported no headache, nausea, or vomiting during the clinical course.

3. Differential Diagnosis, Investigations and Treatment

Head computed tomography demonstrated a 55‐mm mass extending from the subcutaneous tissue to the epidural space with destruction of the frontal bone (Figure 1A–C). MRI was performed using a 3.0‐T scanner. The lesion showed high signal intensity on diffusion‐weighted imaging (Figure 2A) and low signal intensity on the apparent diffusion coefficient map (Figure 2B). The tumor showed low signal intensity on T1‐weighted imaging (Figure 2C) and slightly high signal intensity on T2‐weighted imaging (Figure 2D), with strong and homogeneous enhancement after gadolinium administration (Figure 3).

FIGURE 1.

Computed tomography findings of the cranial vault tumor. (A) Axial non‐contrast head computed tomography demonstrating a large mass in the left frontal region extending from the subcutaneous tissue to the epidural space, associated with destruction of the frontal bone. (B) Axial bone window CT showing osteolytic destruction of the left frontal bone. (C) Three‐dimensional bone CT reconstruction clearly demonstrating the extent of frontal bone destruction.

FIGURE 2.

Magnetic resonance imaging findings of the cranial vault lesion. (A) Axial diffusion‐weighted image showing high signal intensity in the tumor located in the left frontal region. (B) Axial apparent diffusion coefficient map demonstrating low signal intensity within the tumor. (C) Axial T1‐weighted image showing a slightly hypointense mass. (D) Axial T2‐weighted image demonstrating a slightly hyperintense lesion.

FIGURE 3.

Contrast‐enhanced magnetic resonance imaging findings. (A) Axial, (B) coronal, and (C) sagittal gadolinium‐enhanced T1‐weighted images demonstrating strong and relatively homogeneous enhancement of the tumor extending from the subcutaneous region through the skull to the epidural space.

For ¹²³I‐IMP SPECT, 222 MBq of N‐isopropyl‐p‐[¹²³I]iodoamphetamine was administered intravenously. SPECT demonstrated strong ring‐like tracer accumulation corresponding to the tumor on early images (Figure 4A), with further increased uptake on delayed images obtained 4 h after tracer administration (Figure 4B). Laboratory examination showed no significant abnormalities, including a normal soluble interleukin‐2 receptor level.

FIGURE 4.

Preoperative ¹²³I‐IMP SPECT images. (A) Axial early‐phase image demonstrating strong ring‐like tracer accumulation in the tumor (arrowhead). (B) Axial delayed‐phase image obtained 4 h after tracer administration, showing further increased tracer uptake within the lesion (arrowhead).

Based on the marked diffusion restriction and increased tracer uptake on SPECT, malignant lymphoma was considered in the differential diagnosis. Because of skull destruction and the need for cranial reconstruction, tumor removal via craniotomy was performed.

Histopathological examination of the surgically resected tumor was performed using hematoxylin and eosin staining and immunohistochemistry. Hematoxylin and eosin staining demonstrated diffuse proliferation of atypical lymphoid cells with enlarged nuclei, conspicuous nucleoli, and a high nuclear‐to‐cytoplasmic ratio (Figure 5A). Immunohistochemistry showed positivity for CD20 (Figure 5B), CD79α, Bcl‐2, and MUM‐1, and negativity for CD10 and Bcl‐6. CD3 and CD5 were positive in background T lymphocytes. CD138 was negative. The Ki‐67 labeling index was approximately 50%. These findings were consistent with diffuse large B‐cell lymphoma.

FIGURE 5.

Histopathological findings of the tumor. (A) Hematoxylin and eosin staining showing diffuse proliferation of atypical lymphoid cells with enlarged nuclei and conspicuous nucleoli (original magnification ×400). (B) Immunohistochemical staining demonstrating strong, diffuse positivity for CD20 in the tumor cells, consistent with B‐cell lymphoma (original magnification ×400). Scale bars = 50 μm.

Systemic evaluations revealed lymphoma involvement at other sites. After histopathological diagnosis, the patient was referred to another institution for systemic treatment and received Pola‐R‐CHP chemotherapy. According to follow‐up information obtained from the treating physician at the referral institution, no recurrence was observed 13 months after surgery.

4. Conclusion and Results (Outcome and Follow‐Up)

The patient remained recurrence‐free 13 months after surgery. This case suggests that ¹²³I‐IMP SPECT may provide useful adjunctive information for raising suspicion of malignant lymphoma in cranial vault tumors and may contribute to improved preoperative diagnosis.

5. Discussion

Differentiating cranial vault lymphoma from other skull tumors using conventional imaging alone is often difficult because of overlapping radiological features [3, 6, 7, 8]. Cranial vault lymphoma may mimic meningioma, metastatic skull tumors, and other skull lesions because of its relatively nonspecific CT and MRI characteristics [11, 12]. Previous studies have suggested that the pattern of bone involvement may provide an additional diagnostic clue. In particular, cranial vault lymphoma may show a large extracranial and/or intracranial soft‐tissue component despite relatively limited bone destruction, whereas other malignant skull tumors more commonly show extensive bone destruction [6, 12]. In the present case, functional imaging provided additional information that contributed to raising suspicion of malignant lymphoma. Previous studies have suggested that malignant lymphoma may demonstrate relatively high ¹²³I‐IMP uptake compared with other intracranial tumors [9, 10]. Furthermore, persistent or increased uptake on delayed images has been reported as a characteristic finding of malignant lymphoma [9, 10]. In this case, the combination of increased uptake on early images and further accumulation on delayed images was consistent with these characteristics. Previous studies of primary central nervous system lymphoma (PCNSL) have further demonstrated the diagnostic value of delayed ¹²³I‐IMP uptake. Yoshikai et al. evaluated 11 malignant lymphomas and 41 non‐lymphomatous intracranial tumors and found that all lymphomas except one small lesion had delayed tumor‐to‐normal (T/N) ratios greater than 0.9, whereas all non‐lymphomatous tumors had delayed T/N ratios below 0.8 [13]. Shinoda et al. demonstrated that ¹²³I‐IMP retention increased over time in PCNSL and suggested that evaluation of tracer retention may be more useful than assessment of uptake on a single SPECT image [14]. More recently, Osawa et al. reported that delayed‐phase ¹²³I‐IMP SPECT differentiated PCNSL from glioblastoma with a sensitivity of 92.0%, specificity of 88.9%, and area under the curve of 0.945 [15]. However, the relatively low T/N ratio and limited tumor detectability remain disadvantages of ¹²³I‐IMP SPECT [15]. Importantly, these studies primarily involved PCNSL, and the sensitivity and specificity of ¹²³I‐IMP SPECT specifically for cranial vault lymphoma have not been established. Therefore, ¹²³I‐IMP SPECT findings should be regarded as supportive rather than diagnostic in this setting. Unlike previous reports of cranial vault lymphoma that have primarily focused on clinical characteristics and conventional imaging findings [3, 6, 7, 8], the present case highlights increased ¹²³I‐IMP uptake on early images with further accumulation on delayed images as a potential adjunctive imaging clue. Thus, this case suggests that delayed ¹²³I‐IMP retention, previously reported mainly in PCNSL, may also provide adjunctive diagnostic information in lymphoma involving the cranial vault.

[¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography/computed tomography (PET/CT) is another useful functional imaging modality for lymphoma and is particularly valuable for systemic staging and treatment response assessment [16]. Cranial vault lymphomas have also been reported to show FDG uptake [6]. In contrast, ¹²³I‐IMP SPECT may provide different diagnostic information through the characteristic retention or increased uptake of IMP on delayed images reported in malignant lymphoma [9, 10]. Although ¹²³I‐IMP SPECT is not a standard modality for systemic lymphoma staging, evaluation of delayed tracer retention may provide complementary information when lymphoma is included in the differential diagnosis of a cranial vault tumor. However, the diagnostic value of this finding specifically for cranial vault lymphoma remains uncertain because of the limited number of reported cases.

Another important imaging feature was marked hyperintensity on diffusion‐weighted imaging, which reflects high cellular density. The coexistence of diffusion restriction and delayed tracer accumulation may reflect the biological characteristics of lymphoma and may serve as a useful diagnostic clue. From a clinical perspective, early and accurate recognition of cranial vault lymphoma is important because its treatment strategy differs significantly from those for other skull tumors [1, 3, 6, 7, 8, 17, 18]. Previous reports have described cranial vault DLBCL initially suspected to represent meningioma or other skull tumors, illustrating the difficulty and clinical importance of establishing the correct diagnosis [17, 18]. Systemic chemotherapy constitutes an important component of treatment for cranial vault lymphoma, whereas other malignant skull tumors may require extensive surgical resection depending on the underlying pathology. Therefore, raising suspicion of lymphoma before surgery may facilitate appropriate systemic evaluation, histopathological confirmation, and timely initiation of lymphoma‐directed therapy [1, 6, 7, 8]. Although histopathological confirmation remains essential, imaging findings that suggest lymphoma may help narrow the differential diagnosis and guide subsequent diagnostic and therapeutic planning. Earlier recognition may thereby reduce delays in the initiation of appropriate treatment.

This report has several limitations. First, it describes a single case, which limits the generalizability of the imaging findings, and similar findings may be observed in other hypercellular tumors. Second, ¹²³I‐IMP uptake was evaluated qualitatively without quantitative assessment such as measurement of the T/N ratio; therefore, direct comparison with previously reported quantitative findings was not possible. In addition, the sensitivity and specificity of ¹²³I‐IMP SPECT specifically for cranial vault lymphoma remain unknown because previous studies have primarily focused on primary central nervous system lymphoma. Third, the follow‐up period was limited to 13 months, and detailed long‐term follow‐up data were unavailable because subsequent systemic treatment and follow‐up were performed at another institution. Further studies involving larger numbers of patients with cranial vault lymphoma, quantitative assessment of ¹²³I‐IMP uptake, longer follow‐up periods, and comparison with other functional imaging modalities are needed to clarify the diagnostic value and clinical utility of ¹²³I‐IMP SPECT in this setting.

Author Contributions

Yuki Sakaeyama: investigation, data curation, writing – original draft. Yutaka Fuchinoue: investigation, data curation, writing – original draft. Mitsuyoshi Abe: investigation, formal analysis. Shuhei Kubota: investigation, formal analysis. Ryo Matsuzaki: investigation, formal analysis. Sayaka Terazono: investigation, formal analysis. Nobuo Sugo: conceptualization, supervision, writing – review and editing.

Funding

The authors have nothing to report.

Ethics Statement

Ethical approval was not required for this case report in accordance with institutional policy.

Consent

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

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The authors have nothing to report.