Figure 1
Teaching Case
SectionInterventional radiology
Case TypeClinical Cases
AuthorsElie Lteif, M.D.; Fatemeh Behnia, M.D.
Connected authors
61 years, male
A 61-year-old male patient had a histologically proven melanoma treated with local excision and high dose of IL-2.
He had been off-treatment and cancer-free for 2 years when on a follow up FDG PET/CT a 2.4x3.1 cm hilar node with a max SUV of 13.6 was found and boipsied.
He had been off-treatment and cancer-free for 2 years when on a follow up FDG PET/CT a 2.4x3.1 cm hilar node with a max SUV of 13.6 was found and boipsied.
Complete spontaneous histologically proven metastatic melanoma regression post biopsy.
Regression post excision
Regression post treatment
A left hilar node measuring 2.4x3.1 cm with a max SUV of 13.6 was found.
Other tiny lymph nodes with no FDG uptake were noted as well.
Very focal intense FDG uptake corresponding to a normal right round ligament of the femoral head on the concurrent diagnostic CT. This more likely repents a traumatic /inflammatory process as this would be a very uncommon location for metastasis.
A mediastinoscopy for biopsy was performed to confirm the diagnosis.
A histologically proven metastatic melanoma was found.
Two months post biopsy, a re-staging PET/ CT was obtained prior to treatment. During this period, patient refused any treatment and he was already off treatment and cancer free for 2 years.
The PET/CT showed complete regression of the previously described hilar node.
The patient remained disease free.
Other tiny lymph nodes with no FDG uptake were noted as well.
Very focal intense FDG uptake corresponding to a normal right round ligament of the femoral head on the concurrent diagnostic CT. This more likely repents a traumatic /inflammatory process as this would be a very uncommon location for metastasis.
A mediastinoscopy for biopsy was performed to confirm the diagnosis.
A histologically proven metastatic melanoma was found.
Two months post biopsy, a re-staging PET/ CT was obtained prior to treatment. During this period, patient refused any treatment and he was already off treatment and cancer free for 2 years.
The PET/CT showed complete regression of the previously described hilar node.
The patient remained disease free.
The incidence of malignant melanoma has been increasing dramatically during the last decade [1]. The most important prognostic factor is the Breslow classification, which is based on the thickness of the primary lesion [1].
Melanoma can spread haematogenously or via the lymphatic system, although the most common metastatic sites are the lung, brain and bone; melanoma metastases have been reported everywhere [1-8]. FDG PET-CT is highly sensitive for detection of metastatic melanoma due to high uptake values [1-7]. CT examination is likely more sensitive in detecting small parenchymal lung lesions, and MRI remains the modality of choice for evaluation of brain metastases [1].
The sensitivity of the PET examination for detecting melanoma depends on its size [1].
Lesions greater than 1 cm are 95% detected; lesions between 6 and 10 mm are 80 % detected; and for lesions less than 5 mm , there is a less than 20 % chance to detect them [1].
Spontaneous regression of metastatic melanoma can be partial or complete, permanent or
temporary [6-7]. It has to occur in the absence of disease specific treatment [6-7]. The present case may be classified as a complete spontaneous regression according to this definition [6-7].
In rare case reports of malignant spontaneous regression, it seems to be associated with
changes in the immune status of the patient [8]. William B. Coley was the first scientist who noticed this association [13]. He used to induce a febrile illness, either with vaccines or toxins, that triggered the patient's own immune system which resulted in variable success [13]. Matzinger studied the escape of malignant cells from the immune response where there is a deactivation of pathogen-specific molecular patterns to Toll-like receptors that activate tumour-toxic T cells [9].
A review of the literature suggests that metastatic lesions may induce an immune escape through possible mechanisms such as mutation, production of suppressive cytokines, down-regulation of human leukocyte antigen and myeloid-derived suppressor cells [10-12].
In the present case, the spontaneous regression of metastatic hilar lymph node followed the biopsy could be considered to be related to local immunologic factors [14-15]. One potential explanation is via activation of a natural tumour-specific cytolytic T-cell response that is not stimulated in the remaining melanoma metastases [10]. It was recently reported that the immunological process, including certain cytokines, such as tumour necrosis factor and interferon may stimulate cytotoxic function against the malignant cells [11-16]. Another explanation proposes that biopsy can act as mediating and may increase the blood flow and immune response locally [6].
These hypotheses remain obscure and deserve further studies and investigation.
A written informed patient consent for publication has been obtained.
Melanoma can spread haematogenously or via the lymphatic system, although the most common metastatic sites are the lung, brain and bone; melanoma metastases have been reported everywhere [1-8]. FDG PET-CT is highly sensitive for detection of metastatic melanoma due to high uptake values [1-7]. CT examination is likely more sensitive in detecting small parenchymal lung lesions, and MRI remains the modality of choice for evaluation of brain metastases [1].
The sensitivity of the PET examination for detecting melanoma depends on its size [1].
Lesions greater than 1 cm are 95% detected; lesions between 6 and 10 mm are 80 % detected; and for lesions less than 5 mm , there is a less than 20 % chance to detect them [1].
Spontaneous regression of metastatic melanoma can be partial or complete, permanent or
temporary [6-7]. It has to occur in the absence of disease specific treatment [6-7]. The present case may be classified as a complete spontaneous regression according to this definition [6-7].
In rare case reports of malignant spontaneous regression, it seems to be associated with
changes in the immune status of the patient [8]. William B. Coley was the first scientist who noticed this association [13]. He used to induce a febrile illness, either with vaccines or toxins, that triggered the patient's own immune system which resulted in variable success [13]. Matzinger studied the escape of malignant cells from the immune response where there is a deactivation of pathogen-specific molecular patterns to Toll-like receptors that activate tumour-toxic T cells [9].
A review of the literature suggests that metastatic lesions may induce an immune escape through possible mechanisms such as mutation, production of suppressive cytokines, down-regulation of human leukocyte antigen and myeloid-derived suppressor cells [10-12].
In the present case, the spontaneous regression of metastatic hilar lymph node followed the biopsy could be considered to be related to local immunologic factors [14-15]. One potential explanation is via activation of a natural tumour-specific cytolytic T-cell response that is not stimulated in the remaining melanoma metastases [10]. It was recently reported that the immunological process, including certain cytokines, such as tumour necrosis factor and interferon may stimulate cytotoxic function against the malignant cells [11-16]. Another explanation proposes that biopsy can act as mediating and may increase the blood flow and immune response locally [6].
These hypotheses remain obscure and deserve further studies and investigation.
A written informed patient consent for publication has been obtained.
References
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[2] Ricci SB1, Cerchiari U. (2010) Spontaneous regression of malignant tumors: Importance of the immune system and other factors (Review). 941-945 (PMID: 22870091)
[3] Huang TW1, Cheng YL, Chen JC, Tsai WC, Chang H, Lee SC. (2008) Spontaneous regression of a mediastinal thymoma. J Thorac Cardiovasc Surg (PMID: 19380006)
[4] Am J Surg Pathol. 2006 Jul;30(7):858-65. (2006) Spontaneous regression of testicular germ cell tumors: an analysis of 42 cases. Am J Surg Pathol 30(7):858-65 (PMID: 16819328)
[5] Jessy T1. (2011) Immunity over inability: The spontaneous regression of cancer. J Nat Sci Biol Med 2(1):43-9 (PMID: 22470233)
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[8] Imrédi E, Plótár V, Szavcsur P, Pánczél G, Melegh K, Schlachter K, Liszkay G. (2018) Treatment of metastatic progression following the synchronous occurrence of cutaneous and ocular primary melanomas. Orv Hetil 159(16):642-647. (PMID: 29658281)
[9] Matzinger P (1998) An innate sense of danger. Semin Immunol 10(5):399-415. (PMID: 12081934)
[10] Zorn E, Hercend T (1999) A natural cytotoxic T cell response in a spontaneously regressing human melanoma targets a neoantigen resulting from a somatic point mutation. Eur J Immunol 29(2):592-601 (PMID: 10064075)
[11] Shaw HM, McCarthy SW, McCarthy WH, Thompson JF, Milton GW (1989) Thin regressing malignant melanoma: significance of concurrent regional lymph node metastases. Histopathology 15(3):257-65 (PMID: 2807184)
[12] Matsuki R, Sugiyama M, Yoshiike S, Shibahara J, Kogure M, Yokoyama M, Suzuki Y, Abe N, Masaki T, Mori T (2018) Spontaneous regression of colorectal liver metastasis. Clin J Gastroenterol 11(4):263-267 (PMID: 29546568)
[13] Coley WB (1910) The Treatment of Inoperable Sarcoma by Bacterial Toxins (the Mixed Toxins of the Streptococcus erysipelas and the Bacillus prodigiosus). Proc R Soc Med 3(Surg Sect):1-48 (PMID: 19974799)
[14] Zurac S1, Negroiu G, Petrescu S, Andrei R, Tebeica T, Popp C, Musţată R, Neagu M, Constantin C, Solovan C, Chiţu V, Reboşapcă A, Andreescu B, Marinescu I, Stăniceanu F (2012) Spectrum of morphologic alterations of regression in cutaneous melanoma--potential for improving disease prognosis. Rom J Intern Med 50(2):145-53 (PMID: 19974799)
[15] Frankel AE, Rossi P, Kuzel TM, Foss F (2002) Diphtheria fusion protein therapy of chemoresistant malignancies. Curr Cancer Drug Targets 2(1):19-36 (PMID: 12188918)
[16] Tran T, Burt D, Eapen L, Keller OR. (2013) Spontaneous regression of metastatic melanoma after inoculation with tetanus-diphtheria-pertussis vaccine. Curr Oncol 20(3):e270-3 (PMID: 23737697)
Case information
| URL: | https://www.eurorad.org/case/16055 |
| DOI: | 10.1594/EURORAD/CASE.16055 |
| ISSN: | 1563-4086 |
License
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Figure 1
Department of radiology, University of washington, Seattle, USA
Figure 2
Department of radiology, University of washington, Seattle, USA
Figure 3
Department of radiology, University of washington, Seattle, USA
Figure 4
Department of radiology, University of washington, Seattle, USA
Figure 5
Department of radiology, University of washington, Seattle, USA