Spontaneous Regression of a Metastasis from Melanoma: A Case Report

Spontaneous Regression of a Metastasis from Melanoma: A


Introduction
Spontaneous regression (SR) of cancer was initially defined by Stewart, [1] and revised by Cole [2]. According to them "it is the partial or complete disappearance of a malignant tumor in the absence of all treatment or in the presence of therapy which is considered inadequate to exert a significant influence on neoplastic disease". The authors also point out that SR does not mean a complete disappearance of the tumor, nor is it synonymous with cure [1,2]. Furthermore, they emphasize SR is not an adequate term, "because there is obviously a cause of the regression", although it is unknown. The likelihood of SR in melanoma is one of the biggest among all subtypes of cancer. In a collection of 176 cases reported by Cole during the1960's, there were predominately hypernephroma, neuroblastoma and melanoma, with 31, 29 and 19 cases, respectively [2]. Primary lesions regress more frequently than the secondary ones. Some degree of histological regression can be identified in up to 50% of cases [3,4], but a complete disappearance of the tumor happens in a lesser proportion. Some patients present with a metastatic melanoma, but the methods routinely used for staging may be unable to identify the primary site. Several reports from medical literature estimates 4%-6% of those cases [5,6], however, that kind of phenomenon is rarer when the disease present with metastases.
It has been said the first case of SR was described in 1889 [7] and it remains a rare observation. As far as we know, less than one hundred cases of complete regression of metastatic melanoma have been described so far. Conversely, the probability of SR of metastasis from melanoma is less than 1% [8,9]. The exact mechanism of SR in melanoma is not yet fully understood, but immunological factors must be considered. Melanoma cells are known to be immunogenic and to contain tumor-specific antigens which may cause production of circulating humoral antibodies, as well as other immunological reactions.

Case Report
We describe a case of a 69-year-old male patient, diagnosed

Discussion
In this case the metastatic melanoma with SR occurred in a male patient; it is known there is a lesser prevalence of this kind of cancer in females. Lungs are the main visceral sites from which metastases can regress. Both findings are in accordance to medical literature. The characteristics of the patients whose metastases from melanoma reach SR can be mainly withdrawn from an article review published by Kalialis, et al. in 2009 in which they reported 75 cases, since 1866 [10]. Below, these characteristics are described in a summarized form ( Table 1). The patient's age were divided into two groups: more or less 65 years, just to show the proportion of elderly ones. The number between parentheses, whenever present, indicates the real age of the patients. The average age in women is 43.3 years, and in men 56.9. SR occurs more commonly in males than in females; particularly in lesions of trunk in comparison to lesions of other human body areas [7]. Kalialis, et al. still accentuate the most common sites from which metastases can spontaneously regress are cutaneous or subcutaneous tissues, followed by lymph nodes. Other less common sites are, in order of probability, lungs, liver, brain and bowels [7,10]. Remarkably, the main factor associated with SR in virtually all the patients was some kind of operative trauma, followed by infection and radiotherapy.  Complet  55  3  0  0  1  59  70,2   Partial  20  3  1  1  0  25  29,8   Associated factortoSR   Operations  75  6  0  1  1  83  98,8   Infection  21  0  0  0  0  21  25   Radiation  11  0  1  0  0  by cerebral irradiation can also be noticed [11]. The patient we have described underwent a biopsy to clarify the nature of the pulmonary lesion. We believe such procedure ended up releasing some antigens to his immune system. Consequently, there could have been a mobilization of effect or cells to the tumor. Or maybe it was just a coincidence, because the regression was about to occur when the biopsy was performed. In both situations, there should have been a major effectiveness of the immune system.
Unequivocally, the lesion regressed completely, anyway. A similar SR of a metastatic melanoma pulmonary following biopsy has been reported as well [12]. The importance of a surgical procedure in promoting regression in metastatic melanoma can also be illustrated by Bram hall, et al. in a paper published in 2014 [13].
They did a retrospective review over a 15 year period and reported 6 cases of SR of metastatic melanoma. According to their own words, those cases are "clinical evidence of the abs copal effect"surgically induced, we would add.
Many other less relevant factors can be implied. Among them, we can cite BCG (Bacillus Calmette Guérin) and rabies vaccinations, blood transfusions, endocrine factors such as pregnancy or terminations, several alternative therapies, in addition to conditions such as xeroderma pigmentosum, diabetes mellitus, nephrolithias is, prostatic hyperplasia and peptic ulcer [10]. In all the above situations there seems to be a chronic stimulation of the immune system. Anyways, such occurrences are rare. Some factors appear to be involved with the start of cancer regression and others with its maintenance or continuation. The operative trauma is probably related to the beginning of regression. It is hard to make such a statement unequivocally; perhaps it is just a "circumstantial evidence" [13]. The infection rate in patients demonstrating regression of metastatic melanoma can be as high as 28% [14].
There can be a correlation between infection and cancer regression.
Infection, as well as other ways of immune system stimulation, can play some role in increasing the natural defenses against neoplasia. In the past, some breast cancer patients had erysipelas-induced in order to provoke some tumor regression.
Nevertheless, it seems melanoma survival rates are worse in immune suppressed patients than in normal ones [15]. There may also be a regional reduction in immune activity within lymph nodes prior to the development of lymph node metastases [16]. Supposedly, there is a balance between host defenses and proliferation of cells  [20,21].
A somewhat different view of melanoma SR has been recently proposed by Motofei [22]. According to him, that is an excellent model of a "possible autoimmune rejection". In order to support his theory, there is the observation that melanoma SR occurs more frequently in men than women, with a ratio of 2.7:1 [23]. A possible explanation for this observation is that men are not projected "as a host for gestational immune-tolerance". Motofei adds that cancer should no longer be considered a cellular problem as it has been so far; "it is a supra-cellular problem represented by inadequate evolution of complex process such as embryogenesis, development, regeneration, etc. [22].

Conclusion
SR of metastatic disease in melanoma remains poorly understood. There have been some known factors involved in such a process, but we have not been able to select patients for this kind of occurrence. Aught, it seems to be a favorable prognostic factor, even though subsequent relapse may happen. Ultimately, tumor growth regressions are the outcome of a fight between host defenses and promotional factors produced by the tumor itself or in response to its presence. Nowadays, the melanoma treatment goals are to stimulate the immune system, in order to eliminate the malignant cells. Actually, the achievements of immunotherapy in the treatment of melanoma are among the most remarkable developments in cancer therapy over the last decades.