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Clarification of an unclear axillary lesion using multimodal ultrasound diagnostics and AI
Authors: Ulrich Kaiser[1],[2], Ursula Vehling-Kaiser[2], Ernst Michael Jung[3]
[1] Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany
[2] MVZ Dr. Vehling-Kaiser GmbH, Landshut, Germany
[3] Institute of Radiology and Interdisciplinary Ultrasound, University Hospital Regensburg, Regensburg, Germany
Figure 6: B-mode AI: Inhomogeneous, irregular and malignant suspicious formation up to approx. 7 cm in size. Assessment of tumor extent and tumor morphology according to a scheme for artificial intelligence, based on the guidelines for thyroid tumors. Planning and performing an ultrasound punch biopsy.
1Clinical History
We report the case of an 82-year-old female patient who was detected to have a new-onset left axillary lymphadenopathy on contrast-enhanced computed tomography (CT) (Figure 1). The patient suffered from nodular malignant melanoma and had a history of mantle cell lymphoma. The newly occurring lymphadenopathy could be either a relapse of the lymphoma or a metastasis of the malignant melanoma. For further clarification, a multimodal ultrasound diagnostic (B-mode, color coded duplex, elastography and contrast-enhanced ultrasound (CEUS)) was performed, including an ultrasound-guided biopsy after the patient had given her written consent.
2Image Findings
An experienced examiner performed the ultrasound examination using linear multi-frequency probes (5-11 MHz and 6-18 MHz, Resona R9, Mindray). In B-mode, the mass was measured in three planes. The vascularization of the tumorous lesion was analyzed using color coded duplex sonography (CCDS) and ultrasonic microvascularization techniques (UMV) (Figure 2). With shear wave elastography (SWE), the assessment of a possible compaction of the soft tissue tumor was initially color-coded with subsequent measurement using defined regions of interest (Figure 3). CEUS was performed using 2.4 ml of SonoVue® (Bracco, Milan) with 10 ml of NaCl as a bolus injection intravenously via a cubital approach (Figure 4).
The period from the early arterial phase (after 10-15 s) to the venous phase (after 60-70 s) was digitally stored as cine loop. Additional short cine loops (up to 10 s, after every further minute and up to 5 min) were also stored. After recording, the CEUS loop was evaluated for the perfusion analysis of the dynamic tumor vascularization. This included a time intensity curve (TIC) documentation in selected regions in the peripheral and central areas of the lesion and in the surrounding tissue (for comparative analysis) (Figure 5). Selected perfusion parameters such as peak enhancement, time to peak, mean transit time (mTT) and rise time (RT) were determined in different color maps. In addition, an artificial intelligence (AI) tool designed for thyroid diagnostics was used for further characterization (Figure 6).
Overall, there was an echo-inhomogeneous, lobulated and partially infiltrating soft tissue mass up to 6 cm in size, which showed irregular hypervascularization at the margins with a central area poor in vessels. In addition, marginal soft tissue indurations and central necroses were particularly evident. In CEUS, delayed peripheral contrast agent enhancement with subsequent central washout and peripheral irregular microvascularization with central areas of necrosis could be demonstrated.
A targeted, uncomplicated core biopsy was taken under sterile conditions using a 14 G puncture needle from the areas with abnormal contrast on CEUS, with the removal of 2- to 3-cm-long cylindrical cores, which were fixed in formalin (Figure 6).
The period from the early arterial phase (after 10-15 s) to the venous phase (after 60-70 s) was digitally stored as cine loop. Additional short cine loops (up to 10 s, after every further minute and up to 5 min) were also stored. After recording, the CEUS loop was evaluated for the perfusion analysis of the dynamic tumor vascularization. This included a time intensity curve (TIC) documentation in selected regions in the peripheral and central areas of the lesion and in the surrounding tissue (for comparative analysis) (Figure 5). Selected perfusion parameters such as peak enhancement, time to peak, mean transit time (mTT) and rise time (RT) were determined in different color maps. In addition, an artificial intelligence (AI) tool designed for thyroid diagnostics was used for further characterization (Figure 6).
Overall, there was an echo-inhomogeneous, lobulated and partially infiltrating soft tissue mass up to 6 cm in size, which showed irregular hypervascularization at the margins with a central area poor in vessels. In addition, marginal soft tissue indurations and central necroses were particularly evident. In CEUS, delayed peripheral contrast agent enhancement with subsequent central washout and peripheral irregular microvascularization with central areas of necrosis could be demonstrated.
A targeted, uncomplicated core biopsy was taken under sterile conditions using a 14 G puncture needle from the areas with abnormal contrast on CEUS, with the removal of 2- to 3-cm-long cylindrical cores, which were fixed in formalin (Figure 6).
3Diagnosis
Histopathological analysis revealed mantle cell lymphoma with very high proliferative activity.
4Discussion
BACKGROUND:
Mantle cell lymphomas account for a small proportion of lymphomas in Europe. Depending on the form of mantle cell lymphoma, the clinical picture is often heterogeneous. Lymph node enlargement and splenomegaly are common symptoms. Various factors such as the Ki-67 index, TP53 alterations or blood count play a crucial role in assessing the prognosis [1-3].
CLINICAL PERSPECTIVE:
The ultrasound examination showed a mixed echogenic, lobulated soft tissue tumor with central necrosis, fast-growing with irregular hypervascularization at the margins and partial induration. The ultrasound findings indicated a suspected malignant, rapidly proliferating tumor. The applied modified AI supports this assessment. The focus of AI in this context are automatic pattern detection,measurements of diameter and volume, characterization of morphology based on analyzed and stored data volumes.
The following differential diagnoses were considered in the present case:
- Metastasis of malignant melanoma
- Tumor manifestation of breast cancer
- Soft tissue sarcoma
- Cancer of unknown primary (CUP syndrome)
- Lymphoma
In the histopathological examination that was carried out, the diagnosis of mantle cell lymphoma with high proliferation activity (Ki-67 antigen at almost 100%) was finally made and discussed in a subsequent interdisciplinary tumor board with regard to further therapeutic procedures.
THERAPY PLANNING:
In the interdisciplinary tumor board, an antiproliferative systemic therapy close to home, possibly in combination with additional local radiotherapy, was recommended, taking into account the patient's age.
OUTCOME & PROGNOSIS:
Therapy for mantle cell lymphoma is possible in an outpatient setting even in old age. The patient's general state of health, comorbidities and existing medications play an important role in the choice of therapy. In the present case, the result of the planned therapy remains to be seen.
Mantle cell lymphomas account for a small proportion of lymphomas in Europe. Depending on the form of mantle cell lymphoma, the clinical picture is often heterogeneous. Lymph node enlargement and splenomegaly are common symptoms. Various factors such as the Ki-67 index, TP53 alterations or blood count play a crucial role in assessing the prognosis [1-3].
CLINICAL PERSPECTIVE:
The ultrasound examination showed a mixed echogenic, lobulated soft tissue tumor with central necrosis, fast-growing with irregular hypervascularization at the margins and partial induration. The ultrasound findings indicated a suspected malignant, rapidly proliferating tumor. The applied modified AI supports this assessment. The focus of AI in this context are automatic pattern detection,measurements of diameter and volume, characterization of morphology based on analyzed and stored data volumes.
The following differential diagnoses were considered in the present case:
- Metastasis of malignant melanoma
- Tumor manifestation of breast cancer
- Soft tissue sarcoma
- Cancer of unknown primary (CUP syndrome)
- Lymphoma
In the histopathological examination that was carried out, the diagnosis of mantle cell lymphoma with high proliferation activity (Ki-67 antigen at almost 100%) was finally made and discussed in a subsequent interdisciplinary tumor board with regard to further therapeutic procedures.
THERAPY PLANNING:
In the interdisciplinary tumor board, an antiproliferative systemic therapy close to home, possibly in combination with additional local radiotherapy, was recommended, taking into account the patient's age.
OUTCOME & PROGNOSIS:
Therapy for mantle cell lymphoma is possible in an outpatient setting even in old age. The patient's general state of health, comorbidities and existing medications play an important role in the choice of therapy. In the present case, the result of the planned therapy remains to be seen.
5Teaching Points
The occurrence of a lesion of unclear dignity requires prompt further investigation, especially in patients with a known tumor disease history. The combined use of various modern ultrasound techniques (CEUS, multimodal ultrasound, elastography) [4, 5] – where available – allows initial conclusions to be drawn regarding the malignancy/benignancy and proliferation behavior of the mass. However, a histological examination is still necessary in most cases. In addition, the further development of artificial intelligence and its application in ultrasound and, in particular, tumor diagnostics remains to be seen with excitement.
6References
1. Hoster E, Dreyling M, Klapper W et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood 2008;111(2):558-65.
2. Aukema SM, Hoster E, Rosenwald A et al. Expression of TP53 is associated with the outcome of MCL independent of MIPI and Ki-67 in trials of the European MCL Network. Blood 2018;131(4):417-20.
3. Hoster E, Rosenwald A, Berger F et al. Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network. Journal of Clinical Oncology 2016;34(12):1386-94.
4. Jung EM, Kaiser U, Herr W et al. Novel high-resolution contrast agent ultrasound techniques HiFR CEUS and SR CEUS in combination with shear wave elastography, fat assessment and viscosity of liver parenchymal changes and tumors. Clin Hemorheol Microcirc 2024;86(3):263-73.
5. Jung EM, Wiesinger I, Kaiser U et al. Initial experiences with dynamic, quality indicator-based multimodal tissue analysis (M-Ref) with parallel assessment of viscosity and shear wave elastography in liver parenchyma alterations. Clin Hemorheol Microcirc 2024;88(4):419-27.
2. Aukema SM, Hoster E, Rosenwald A et al. Expression of TP53 is associated with the outcome of MCL independent of MIPI and Ki-67 in trials of the European MCL Network. Blood 2018;131(4):417-20.
3. Hoster E, Rosenwald A, Berger F et al. Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network. Journal of Clinical Oncology 2016;34(12):1386-94.
4. Jung EM, Kaiser U, Herr W et al. Novel high-resolution contrast agent ultrasound techniques HiFR CEUS and SR CEUS in combination with shear wave elastography, fat assessment and viscosity of liver parenchymal changes and tumors. Clin Hemorheol Microcirc 2024;86(3):263-73.
5. Jung EM, Wiesinger I, Kaiser U et al. Initial experiences with dynamic, quality indicator-based multimodal tissue analysis (M-Ref) with parallel assessment of viscosity and shear wave elastography in liver parenchyma alterations. Clin Hemorheol Microcirc 2024;88(4):419-27.
