Not always a miracle - The case of the missing metastasis.

Spontaneous regression of malignant neoplasms is extremely rare, but renal cell carcinomas (RCC) are most often associated with this phenomenon. We report a case of a patient with personal history of RCC, who underwent nephrectomy and no other oncological treatment. One year after nephrectomy, a lung metastasis was detected and kept under follow-up for 3 years. Its size increased over time until a needle biopsy was performed, and its metastatic nature confirmed. Wedge resection of the lung nodule was performed, and no neoplastic cells were found, suggesting its spontaneous regression after biopsy. Different theories have been proposed to explain this phenomenon and, in most cases, the mechanism seems to involve the activation of the immune system. This case supports the importance of reducing tumor burden and the impact of the disturbance of the tumor microenvironment caused by instrumentation, in improving immune system activation and its essential role in neoplasm regression.

Spontaneous regression of primary cutaneous diffuse large B-cell lymphoma, leg type: A case series and review of the literature.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is a subtype of cutaneous B-cell lymphoma with unfavorable prognosis usually requiring aggressive polychemotherapy for disease control. Only single cases of spontaneous regression of PCDLBCL, LT are reported in the literature, peaking 3 months post-biopsy following a clinical history of no longer than 1 year. Here, we report the first case of a spontaneously relapsing and remitting PCDLBCL, LT with complete regression after a clinical history of more than 9 years and thus an atypically indolent clinical course. The female patient presented with recurrent erythematous, non-ulcerated, non-raised plaques of the right lower leg for 6 years. Pathological workup and exclusion of a systemic disease confirmed the diagnosis of PCDLBCL, LT. Due to the history of repeated spontaneous remission, no therapy was initiated. Nine years after first occurrence the patient presented with complete clinical remission lasting for 64 months. We retrospectively identified four additional PCDLBCL, LT patients with spontaneous remission lasting up to 53 months. Our data provide evidence for a distinct PCDLBCL, LT patient subgroup that clinicians should be aware of and warrants a watch-and-wait treatment regime.

SPONTANEOUS REGRESSION OF HEPATOCELLULAR CARCINOMA: FOCUSING IN THE ASSOCIATED RISK FACTORS.

BACKGROUND: Spontaneous regression (SR) is defined as the partial or complete disappearance of a tumor, in the absence of a specific treatment. Evidence of the SR in hepatocellular carcinoma (HCC) is rare. OBJECTIVE: The authors aimed to review all the cases of SR of HCC in two reference centers of Southern Brazil, highlighting the main characteristics. METHODS: Data of all patients with HCC were retrospectively reviewed looking for the occurrence of SR in patients from two tertiary centers in Southern Brazil, in the last five years. The diagnosis of cirrhosis was established according to clinical, laboratory and imaging data, as well as upper endoscopy or histopathological examination when necessary. The diagnosis of HCC was based on typical findings according to radiologic criteria (LIRADS) or histopathological examination. Spontaneous regression was defined as a partial or complete involution of a HCC in the absence of a specific therapy. RESULTS: From all cases of HCC in the last 5 years (n=433), there were five cases of SR. Three (60%) were men, the mean age was 62.6 (50.0-76.0) years, and the etiology was HCV in 3 (60%). Complete regression was observed in three patients (60%), one patient (20%) presented partial regression, and one (20%) relapesed and died. The time of follow-up varied between 12 and 21 months. In this presentation, it was highlighted one case of SR observed after COVID-19 infection in a patient with cirrhosis. The possible mechanisms involved in this situation were reviewed, emphasizing the most common like hypoxia and immunological. There were also one patient submitted to a surgical procedure as a possible fator involved and three patients without obvious risk factors. CONCLUSION: This phenomenon will possibly contribute to a better understanding of the pathophysiological mechanisms of HCC.

Progression to Lymph Node Metastasis After Spontaneous Regression of Pulmonary Adenocarcinoma Following Biopsy.

BACKGROUND/AIM: Spontaneous regression (SR) of cancer, which indicates the natural disappearance of malignant tumors, is rare. Little is known about the mechanisms underlying SR; however, immunological reactions, infections, injuries, and medications have been presumed. Among previously reported cases of SR, lung cancer cases have been extremely limited. CASE REPORT: Here, we present a case of lymph node metastasis exacerbation after SR of a primary adenocarcinoma following a biopsy. After complete disappearance of the primary site tumor, metastatic lymph nodes in the mediastinum gradually increased in size as a single lesion. Local treatment with resection and radiotherapy was effective for this metastasis, without recurrence for >3 years. CONCLUSION: This is an interesting case of SR of pulmonary adenocarcinoma with inconsistent features in the primary and metastatic lesions. When physicians encounter exacerbation of metastatic sites with SR of the primary site in lung cancer, local intervention may be considered as a curative treatment.

Spontaneous regression of multiple solitary plasmacytoma harboring Epstein-Barr virus: a case report and literature review.

We report a rare case of spontaneous regression (SR) in an elderly untreated patient with multiple solitary plasmacytoma (MSP). Diagnosis of MSP was confirmed through surgical resection of the left nasal cavity mass and subsequent biopsy of the right humerus. The patient was considered ineligible for chemotherapy due to poor performance status. At 3-month post-diagnosis, the patient's condition worsened with deteriorating bone lesions and emergence of a new serum monoclonal protein. However, these clinical findings completely disappeared at 6 months, and positron emission tomography-computed tomography at 1 year confirmed complete metabolic remission. Notably, peripheral blood lymphocyte counts were inversely correlated with tumor progression and remission. Pathological re-evaluation of the initial biopsy specimens revealed programmed cell death protein 1 (PD-1) expression in tumor-infiltrating CD8+ T cells. In addition, tumor cells were infected with Epstein-Barr virus (EBV) but were negative for programmed cell death ligand 1 (PD-L1) expression, which is the most potent immune escape mechanism in tumor cells. While the mechanism underlying SR remains unclear, our findings suggest that host immune response as well as EBV infection may contribute to SR. Further studies are needed to elucidate the clinicopathologic mechanisms of tumor regression in plasma cell neoplasms.

Malignant features of minipig melanomas prior to spontaneous regression.

In MeLiM minipigs, melanomas develop around birth, can metastasize, and have histopathologic characteristics similar to humans. Interestingly, MeLiM melanomas eventually regress. This favorable outcome raises the question of their malignancy, which we investigated. We clinically followed tens of tumors from onset to first signs of regression. Transcriptome analysis revealed an enrichment of all cancer hallmarks in melanomas, although no activating or suppressing somatic mutation were found in common driver genes. Analysis of tumor cell genomes revealed high mutation rates without UV signature. Canonical proliferative, survival and angiogenic pathways were detected in MeLiM tumor cells all along progression stages. Functionally, we show that MeLiM melanoma cells are capable to grow in immunocompromised mice, with serial passages and for a longer time than in MeLiM pigs. Pigs set in place an immune response during progression with dense infiltration by myeloid cells while melanoma cells are deficient in B2M expression. To conclude, our data on MeLiM melanomas reveal several malignancy characteristics. The combination of these features with the successful spontaneous regression of these tumors make it an outstanding model to study an efficient anti-tumor immune response.

Burnt out testicular tumor - A case report.

ABSTRACT: Spontaneous regression of testicular tumors known as burnt-out tumor of testis is a rare entity and is seen in about 5% of testicular germ cell tumors. It is described as a spontaneously, completely, or partially regressed testicular tumor with or without metastasis in the absence of any treatment. This entity is now included in the 2016 classification of testicular tumors. This is probably only the second case presented in India. High degree of awareness of this entity by the pathologist, clinician, and radiologist is necessary for proper management and survival of the patient.

Câncer materno: a compreensão da criança e suas representações / Maternal cancer: the child's understanding and its representations / Cáncer materno: comprensión del niño y sus representaciones

O câncer é uma doença crônico-degenerativa, que tem como uma de suas principais características a capacidade de invadir tecidos e órgãos do corpo, favorecendo o crescimento desordenado de células. É uma doença que impacta fortemente a pessoa enferma e todos à sua volta, incluindo sua família e seus amigos. A partir desse cenário, este trabalho visou compreender a visão da criança e o impacto emocional sofrido diante do diagnóstico de câncer da mãe. Buscou-se avaliar, a partir de ferramentas lúdicas e do desenho-estória, o entendimento da criança em relação ao processo de adoecimento materno, tomando como base o referencial psicanalítico para reconhecer como ela lidou com a situação. Participaram desta pesquisa uma mulher de 39 anos com diagnóstico de câncer em remissão e seu filho de 9 anos. Os resultados demonstraram que o adoecimento materno causou impactos emocionais significativos e assustadores para o infante, gerando fantasias irreais relacionadas ao câncer e a si próprio. Dessa forma, considera-se de fundamental importância o cuidado estendido aos familiares do indivíduo doente, a fim de que se tenha um olhar a todos que sofrem diante desse contexto.(AU)

Cancer is a chronic-degenerative disease that has as one of its main characteristics the ability to invade tissues and organs of the body, favoring the disordered cell growth. It is a disease that strongly impacts the sick person and everyone around them, including their family and friends. Based on this scenario, this work aimed to understand the child's view and the emotional impact suffered in the face of the mother's cancer diagnosis. It sought to evaluate, with ludic tools and drawing history, the child's understanding about the mother's illness process, based on the psychoanalytic framework to recognize how they deal with the situation. A 39-year-old woman diagnosed with cancer, in remission, and her 9-year-old son participated in this research. The results showed that the maternal illness caused significant and frightening emotional impacts for the infant, creating unrealistic fantasies related to cancer and to himself. Thus, the care extended to the sick individual's family and to the relatives is considered of fundamental importance, to give a complete care for all those who suffer in this context.(AU)

El cáncer es una enfermedad crónico-degenerativa, que tiene como una de sus principales características la capacidad de invadir tejidos y órganos, favoreciendo un crecimiento desordenado de las células. Enfermedades como esta impactan fuertemente a la persona que está enferma y a todos los que la rodean, incluidos familiares y amigos. Considerando esta situación, este estudio tuvo como objetivo comprender la percepción de un niño y el impacto emocional que sufrió ante el diagnóstico del cáncer vivido por su madre. Se pretendió evaluar, utilizando herramientas lúdicas y de dibujo-cuento, la comprensión del niño al proceso de enfermedad materna, buscando reconocer cómo el niño manejó este proceso a partir del referencial teórico psicoanalítico. En esta investigación participaron una mujer de 39 años diagnosticada de cáncer en remisión y su hijo de 9 años. Los resultados mostraron que los impactos emocionales de la enfermedad materna fueron significativos y aterradores para el infante, generando fantasías irreales relacionadas con el cáncer y él mismo. De esta forma, el cuidado extendido a la familia del individuo que está enfrentando esta enfermedad es importante para promover una atención integral a quienes la padecen en este contexto.(AU)

Spontaneous Volumetric Tumor Regression During Wait-and-Scan Management of 952 Sporadic Vestibular Schwannomas.

OBJECTIVE: Spontaneous tumor shrinkage during wait-and-scan management of sporadic vestibular schwannoma is generally considered an uncommon phenomenon. However, most data informing this understanding stem from single-slice linear tumor measurements taken in the axial imaging plane. The objective of the current work was to characterize the regression capacity of sporadic vestibular schwannomas using volumetric tumor measurements. STUDY DESIGN: Retrospective cohort study using slice-by-slice, three-dimensional volumetric tumor measurements. SETTING: Three tertiary referral centers. PATIENTS: Patients with sporadic vestibular schwannoma. INTERVENTIONS: Wait-and-scan. MAIN OUTCOME MEASURES: Regression-free survival rates with regression defined as a decrease of at least 20% of the tumor volume. RESULTS: Among 952 patients undergoing a total of 3,505 magnetic resonance imaging studies during observation, 123 experienced volumetric tumor regression after diagnosis at a median of 1.2 years (interquartile range, 0.6-2.9 yr). Volumetric regression-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after diagnosis were 94% (92-95%; 662), 86% (83-89%; 275), and 78% (73-82%; 132), respectively. Among 405 patients who demonstrated an initial period of tumor growth but continued wait-and-scan management, 48 experienced volumetric regression at a median of 1.2 years (interquartile range, 0.8-2.6 yr) after initial growth. Volumetric regression-free survival rates at 1, 3, and 5 years after initial growth were 94% (92-97%; 260), 84% (79-89%; 99), and 75% (67-83%; 43), respectively. Ultimately, only 82 of the 952 patients studied showed exclusively volumetric tumor regression (i.e., without any periods of tumor growth) by the time of last follow-up. CONCLUSION: Spontaneous volumetric tumor shrinkage during wait-and-scan management occurs more frequently than suggested by previous studies using linear tumor measurements and can even occur after previous episodes of documented tumor growth. These data further highlight the dynamic nature of vestibular schwannoma growth. To this end, the application of natural history data to patient management requires a nuanced approach that parallels the complex tumor behavior of vestibular schwannoma.

Spontaneous Regression of Laryngeal Squamous Cell Carcinoma After Biopsy.

Approximately 7 cases of spontaneous regression of adult laryngeal carcinoma have been published in the literature since 1900. This case presents a 62-year-old male with a 6-month history of hoarseness who was subsequently diagnosed with a T1aN0M0 left true vocal fold squamous cell carcinoma (SCC) after biopsy. One month following the initial biopsy, histopathological findings on repeat biopsy revealed absence of malignancy and regression of the tumor without radiation. There has been no evidence of tumor recurrence. This case exemplifies how innate immune modulation may play a role in the spontaneous regression of laryngeal SCC, although the mechanism remains unknown.

Role of FoxP3-positive regulatory T-cells in regressive and progressive cervical dysplasia.

PURPOSE: Forkhead Box Protein 3 (FoxP3) is known as a key mediator in the immunosuppressive function of regulatory T-cells (Tregs). The aim of our study was to investigate whether FoxP3-positive Tregs have the potential to act as an independent predictor in progression as well as in regression of cervical intraepithelial neoplasia, especially in patients with intermediate cervical intraepithelial neoplasia (CIN II). METHODS: Nuclear FoxP3 expression was immunohistochemically analysed in 169 patient samples (CIN I, CIN II with regressive course, CIN II with progressive course, CIN III). The median numbers were calculated for each slide and correlated with the histological CIN grade. Statistical analysis was performed by SPSS 26 (Mann-Whitney U test, Spearman's rank correlation). RESULTS: An increased FoxP3 expression in CIN II with progression could be detected in comparison to CIN II with regression (p = 0.003). Total FoxP3 expression (epithelium and dysplasia-connected stroma) was higher in more advanced CIN grades (p < 0.001 for CIN I vs. CIN II; p = 0.227 for CIN II vs. CIN III). A positive correlation could be detected between FoxP3-positive cells in epithelium and total FoxP3 expression (Spearman's Rho: 0,565; p < 0.01). CONCLUSION: Expression of FoxP3 could be a helpful predictive factor to assess the risks of CIN II progression. As a prognosticator for regression and progression in cervical intraepithelial lesions it might thereby help in the decision process regarding surgical treatment vs. watchful waiting strategy to prevent conisation-associated risks for patients in child-bearing age. In addition, the findings support the potential of Tregs as a target for immune therapy in cervical cancer patients.

Predicting regression of cervical intraepithelial neoplasia grade 2 in women under 25 years.

BACKGROUND: A number of retrospective and prospective studies have documented substantial rates of regression in cervical intraepithelial neoplasia grade 2 lesions in young women. Initial observational management of cervical intraepithelial neoplasia grade 2 is increasingly accepted as appropriate for women under 25 years of age with screen-detected abnormalities and is included in a number of clinical guidelines. However, there has been a paucity of large prospective studies on observational management with strict inclusion criteria. A number of important questions remain, specifically regarding the clinical variables that are associated with the risk of progression or persistence of disease. To investigate these factors and to ensure that young women with cervical intraepithelial neoplasia grade 2 undergoing observational management were being managed in a well-monitored and an appropriately informed fashion, we conducted a large, multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 in women under 25 years. OBJECTIVE: This study aimed to determine the regression rates and clinical, cytologic, and pathologic predictors of regression of cervical intraepithelial neoplasia grade 2 in women under 25 years undergoing observational management over 24 months. STUDY DESIGN: This study was a multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 (ie, repeat colposcopy, cytology, and cervical biopsy every 6 months) for up to 24 months. A total of 615 consenting women under 25 years with newly-diagnosed, biopsy-proven cervical intraepithelial neoplasia grade 2 were recruited (from 2010 to 2016) through 16 hospital-based colposcopy units in New Zealand and Australia. RESULTS: At completion, 326 women had confirmed regression, 156 had persistent high-grade cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ, and 24 had unconfirmed regression (ie, first regression at the 24-month follow-up). A total of 109 women did not complete the protocol (41 because of delayed follow-up, 41 lost to follow-up, 22 elected treatment, 4 refused a biopsy, and 1 died of an unrelated cause). Confirmed regression was observed in 53% (326 of 615) of all women enrolled in the study and, when missing data were imputed, it was estimated that 64% of women (95% confidence interval, 60%-68%) would have experienced regression. Similarly, lesions regressed in 64% (326 of 506) of women who completed the observational protocol. Based on a multivariable analysis, detection of human papillomavirus 16 in a liquid-based cytology sample at the time of initial colposcopy decreased the chance of regression by 31% (risk ratio, 0.69; 95% confidence interval, 0.56-0.86; P<.001). In addition, at initial colposcopy, low-grade or normal colposcopic impression, later year of diagnosis, low-grade or normal cytology, and being a nonsmoker were all independently associated with an increased chance of regression. CONCLUSION: More than half of women under 25 years with cervical intraepithelial neoplasia grade 2 will regress to cervical intraepithelial neoplasia grade 1 or normal within 24 months without destructive treatment. The absence of human papillomavirus 16 is the most important predictor of regression.

Spontaneous regression of solitary osteochondromas in children: An option to consider in clinical practice.

Osteochondromas are neoplasm that belong to the family of cartilaginous histogenesis tumors and represent 90% of all forms of exostoses. As most osteochondromas are asymptomatic, underdiagnosis is frequent. Symptomatic forms usually manifest before the age of 20 years, and the most common symptoms are pain and the detection of a bony mass. Herein, we report four cases of spontaneous regression of solitary osteochondromas in the light of literature. We consider that orthopedic surgeons should take into account the possibility of spontaneous regression of these tumors, before recommending surgery. Symptoms are usually mild and we recommend following these patients with X-ray and physical examination annually.

Regression is significantly associated with outcomes for patients with melanoma.

BACKGROUND: The prognostic significance of regression in melanoma is debated. We present a large multicenter study correlating regression with sentinel lymph node metastasis and melanoma-specific survival. METHODS: The Sentinel Lymph Node Working Group database was reviewed from 1993 to 2018. Patients with known regression and sentinel lymph node status were included. Clinicopathologic factors were correlated with regression, sentinel lymph node status, and melanoma-specific survival. RESULTS: There were 4,790 patients; median follow-up was 39.6 months. Regression was present in 1,081 (22.6%) cases, and 798 (16.7%) patients had sentinel lymph node metastases. On multivariable analysis, male sex, truncal tumors, and decreasing thickness were significantly associated with regression (P < .05), whereas head/neck or leg tumors had lower rates of regression (P < .05). Regression was significantly correlated with a decreased risk of sentinel lymph node disease on multivariable analysis (odds ratio 0.68, 95% confidence interval 0.54-0.85; P = .0008). Multivariable analysis also showed that increasing age, male sex, increasing thickness, ulceration, lymphovascular invasion, microsatellitosis, and sentinel lymph node metastasis were significantly (P < .05) associated with worse melanoma-specific survival, while regression was significantly associated with better melanoma-specific survival (hazard ratio 0.75, 95% confidence interval 0.57-0.99; P = .043). CONCLUSION: This large study shows that regression is significantly associated with better outcomes in patients with melanoma and is correlated with a lower risk of sentinel lymph node metastasis and a better melanoma-specific survival.

Five-year follow-up and clinical outcome in euthyroid patients with thyroid nodules.

BACKGROUND: Thyroid nodule diagnosis has become increasingly frequent. Defining optimum surveillance intervals for patients with unsuspicious thyroid nodules remains a challenge. This was a single centre cohort study in which patients diagnosed with unsuspicious thyroid nodules in whom no treatment was indicated were invited for re-evaluation 5 years after the diagnosis. The primary end point of the study was to estimate the change in nodule size with thyroid ultrasound (US) and the secondary end point was to assess the need for clinical management 5 years after the diagnosis. PATIENTS AND METHODS: Baseline patient parameters and ultrasound characteristics of the nodules were retrospectively collected. At follow-up, thyroid ultrasound was performed. RESULTS: A hundred and eighteen (107 women / 11 men, aged 56.8 ± 13.4 years) patients were included in the study having 203 nodules at baseline, with mean largest nodule diameter 10.5 ± 7.4 mm. After 5 years, 58 (28.6%) nodules significantly increased in size, 27 (13.3%) decreased, and for 104 (51.2%) of nodules, no change in size was noted. Fourteen (6.9%) nodules disappeared. Additional 26 new nodules (mean largest diameter 7.7 ± 5.0 mm) in 16 patients were identified at follow-up. Regarding the clinical outcome, no new thyroid cancers were found. For 107 (90.7%) patients no further management was indicated. Five (4.2%) patients were referred to thyroidectomy because of the growth of the nodules. Two (1.7%) patients were treated for hyperthyroidism. Four (3.4%) patients did not complete the study. CONCLUSIONS: We report a single centre experience of the natural history of unsuspicious thyroid nodules. Our results showed that 71.4% of such nodules remained stable in size, decreased or even disappeared and that the vast majority of the patients remained clinically stable with no need for treatment 5 years after the diagnosis.