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.

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.

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 a Pulmonary Metastasis Secondary to Contralateral Metastasectomy.

Spontaneous regression is defined as the partial or complete resolution of a malignant neoplasm either with treatment that is perceived to be inadequate or in the absence of therapy. This report describes a case of spontaneous regression of a pulmonary metastasis of renal cell carcinoma secondary to metastasectomy in the contralateral lung.

Mathematical simulation of tumour angiogenesis: angiopoietin balance is a key factor in vessel growth and regression.

Excessive tumour growth results in a hypoxic environment around cancer cells, thus inducing tumour angiogenesis, which refers to the generation of new blood vessels from pre-existing vessels. This mechanism is biologically and physically complex, with various mathematical simulation models proposing to reproduce its formation. However, although temporary vessel regression is clinically known, few models succeed in reproducing this phenomenon. Here, we developed a three-dimensional simulation model encompassing both angiogenesis and tumour growth, specifically including angiopoietin. Angiopoietin regulates both adhesion and migration between vascular endothelial cells and wall cells, thus inhibiting the cell-to-cell adhesion required for angiogenesis initiation. Simulation results showed a regression, i.e. transient decrease, in the overall length of new vessels during vascular network formation. Using our model, we also evaluated the efficacy of administering the drug bevacizumab. The results highlighted differences in treatment efficacy: (1) earlier administration showed higher efficacy in inhibiting tumour growth, and (2) efficacy depended on the treatment interval even with the administration of the same dose. After thorough validation in the future, these results will contribute to the design of angiogenesis treatment protocols.

Rare Case of a Disappearing Pituitary Adenoma During the Coronavirus Disease 2019 (COVID-19) Pandemic.

We present a case of a 28-year-old woman with a history of severe headaches and pituitary insufficiency. She was found to have a large, enhancing, sellar mass consistent with a pituitary adenoma. The patient's surgical care was delayed due to the coronavirus disease 2019 (COVID-19) pandemic, and follow-up imaging revealed spontaneous involution of the sellar mass. Spontaneous involution of pituitary masses has been described but not often encountered in clinical practice. This case highlights that follow-up imaging is necessary when scheduling elective surgeries during the COVID-19 pandemic.

Regresión de tumor pardo en adenoma paratiroideo / Brown tumor regression in parathyroid adenoma

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Reporting regression in primary cutaneous melanoma. Part 2: prognosis, evaluation and management.

The effect of histological regression on patient prognosis for primary cutaneous melanoma is controversial. Some authors hypothesize that regression indicates a robust systemic immune response and may decrease risk of metastasis. Others argue that histological regression calls into question a T0 diagnosis because there may have been an invasive component of the melanoma that is no longer visible but is still active. The literature to date does not suggest that histological regression is associated with increased risk of positive sentinel lymph node status, metastasis or increased risk of mortality. Thus, the presence of histological regression should not change patient staging, evaluation or management. The criteria used for reporting regression have varied dramatically across studies, and standardized reporting is needed to foster evidence-based practices in the future.

Optical coherence tomography (OCT) to image active and inactive retinoblastomas as well as retinomas.

PURPOSE: To illustrate Optical Coherence Tomography (OCT) images of active and inactive retinoblastoma (Rb) tumours. METHODS: Current observational study included patients diagnosed with retinoblastoma and retinoma who were presented at Amsterdam UMC and Jules-Gonin Eye Hospital, between November 2010 and October 2017. Patients aged between 0 and 4 years were imaged under general anaesthesia with handheld OCT in supine position. Patients older than 4 years were imaged with the conventional OCT (Heidelberg Engineering, Heidelberg Spectralis, Germany). All patients included were divided into two groups: active and inactive tumours (retinoma and regression patterns). Patients' medical records and OCT images were analysed during meetings via discussions by ophthalmologists and physicists. RESULTS: Twelve Dutch and 8 Swiss patients were divided into two groups: 2 patients with active tumour versus 18 patients with inactive tumour. Subsequently, inactive group could be divided in two groups, which consisted of 10 patients with retinoma and 8 patients with different regression pattern types. Of all included patients, 15 were male (75%). Median age at diagnosis was 18.0 months (range 0.19-715.2 months). A total of 12 retinoblastoma (active and inactive) and 8 retinoma foci were investigated by OCT. No distinction could be made between active and inactive tumours using only OCT. CONCLUSION: Optical coherence tomography alone cannot distinguish between active and inactive Rbs. However, handheld OCT adds useful information to the established imaging techniques in the monitoring and follow-up of retinoblastoma patients. With this study, we provide an overview of OCT images of active and inactive Rbs.

Spontaneous Regression of Primary Thyroid Lymphoma: Two Rarities at the Same Time.

Primary thyroid lymphomas are pretty uncommon, and constitute about 5% of the neoplasms of this organ. Spontaneous tumor regression is defined as the total or partial disappearance of a tumor as proven by microscope without treatment or under inadequate treatment. It is estimated to happen in one out of 60,000-100,000 cases. We present a case of primary thyroid lymphoma with spontaneous regression after diagnostic puncture and corroborated with hemithyroidectomy at four months. The patient died after twenty-six months of follow-up because of endocarditis and there was no relapse at any time.

Radiologic Features of Spontaneous Regression of Vestibular Schwannomas.

BACKGROUND: Vestibular schwannoma (VS) is the most common benign tumor originating in the cerebellopontine angle. In most cases, tumors tend to grow and deserve proper treatment. Sometimes they stabilize, and rarely they decrease in size spontaneously. METHODS: We evaluated retrospectively the images of patients with spontaneous tumor regression. We describe the common neuroimage findings of patients with spontaneous tumoral regression. RESULTS: Four patients with diagnosis of VS were followed with magnetic resonance imaging (MRI). There were some relevant features in MRI: a heterogeneous contrast enhancement in the outer layer of the tumor and presence of a cerebrospinal fluid column between the tumor and the entrance of the internal auditory canal. The percentage of tumor diameter reduction ranged from 20% to 40%. CONCLUSIONS: Some MRI features may demonstrate a spontaneous involution of VS and may be closely followed in asymptomatic or oligosymptomatic patients.

Neuroblastoma stage 4S: Tumor regression rate and risk factors of progressive disease.

BACKGROUND: The clinical course of neuroblastoma stage 4S or MS is characterized by a high rate of spontaneous tumor regression and favorable outcome. However, the clinical course and rate of the regression are poorly understood. METHODS: A retrospective cohort study was performed, including all patients with stage 4S neuroblastoma without MYCN amplification, from two Dutch centers between 1972 and 2012. We investigated the clinical characteristics, the biochemical activity reflected in urinary catecholamine excretion, and radiological imaging to describe the kinetics of tumor regression, therapy response and outcome. RESULTS: The cohort of 31 patients reached a 10-year overall survival of 84% ± 7% (median follow-up 16 years; range, 3.3-39). During the regressive phase, liver size normalized in 91% of the patients and catecholamine excretion in 83%, both after a median of two months (liver size: range, 0-131; catecholamines: range, 0-158). The primary tumors completely regressed in 69% after 13 months (range, 6-73), and the liver architecture normalized in 52% after 15 months (range, 5-131). Antitumor treatment was given in 52% of the patients. Interestingly, regression rates were similar for treated and untreated patients. Four of seven patients < 4 weeks old died of rapid liver expansion and organ compression. Three patients progressed to stage 4, 3 to 13 months after diagnosis; all had persistently elevated catecholamines. CONCLUSION: Patients < 4 weeks old with neuroblastoma stage 4S are at risk of fatal outcome caused by progression of liver metastases. In other patients, tumor regression is characterized by a rapid biochemical normalization that precedes radiological regression.

Melanocytic aggregates with unique morphology associated with regression of basal cell carcinoma.

BACKGROUND: Spontaneous regression of basal cell carcinomas (BCC) is a well-documented phenomenon. In practice, we have observed melanocytic aggregates associated with BCC at various stages of regression showing unique morphologic features. METHODS: Fourteen cases featuring melanocytic aggregates were retrospectively identified through a pathology database search. Clinical and histopathologic features were systematically evaluated, and additional immunohistochemical studies were performed. Melanocyte density within tumor nodules was compared to a group of control BCCs. RESULTS: All cases showed BCC at various stages of regression with associated melanocytic aggregates, as highlighted by Melan-A and SOX10 immunostains. Three of 14 cases (21.4%) had only dermal melanocytic nests, while 11 (78.6%) had both junctional and dermal nests. The melanocytic aggregates all had similar asymmetrical architecture and lacked maturation. The melanocytes were small, uniform, bland, and had minimal cytoplasm. Their nuclei were overlapping and hyperchromatic, and had inconspicuous nucleoli. None of the melanocytic aggregates stained for BRAFV600E by immunohistochemistry. No patient developed a recurrent or metastatic melanocytic lesion (median follow-up 42 months). Melanocyte density was higher in the case series than in the control BCCs (P = 0.0008). CONCLUSION: We described the unique morphology of melanocytic aggregates associated with BCC regression.

Spontaneous partial regression of a microcystic jejunal mesenteric lymphangioma and a proposed management algorithm.

Mesenteric lymphangiomas are relatively rare, with clinical symptoms ranging from an asymptomatic presentation to an acute abdomen. The natural history and biological behaviour of this entity can range from slow indolent lesions to aggressive tumours with a risk of malignant transformation. Spontaneous regression of a mesenteric lymphangioma is rare. We herein report a case of a jejunal mesenteric lymphangioma that was initially detected incidentally in an asymptomatic patient with a subsequent sudden increase in size with resulting surrounding mass effect after 9 months and a spontaneous partial regression at surgical resection. Our case is the first reported case which outlines a period in the natural history and evolution of microcystic mesenteric lymphangioma, illustrating the sudden enlargement likely attributable to spontaneous and self-limiting haemorrhage and subsequent partial regression at surgical resection. We thenceforth propose a possible management algorithm for adult patients with mesenteric lymphangiomas.

How to radiologically identify a spontaneous regression of sporadic vestibular schwannoma?

BACKGROUND: The natural history of sporadic vestibular schwannoma is unpredictable, with tumors growing, non-growing and even showing spontaneous regression in some rare cases. OBJECTIVE: This retrospective study aims to describe the radiologic signs characterizing and identifying the shrinking vestibular schwannoma. METHODS: Involution was considered to have occurred if tumor size had decreased by 2 mm or more on its largest diameter. All magnetic resonance imaging scans were reviewed for tumor size, internal auditory meatus size, and tumor characteristics. Volumetric measurements were performed on the first and last scan. Audiometric data were collected at the first and last visit. RESULTS: Fourteen patients with a confirmed spontaneous regression were included, with a mean follow-up of 5 ± 2.6 years. The mean shrinkage rate was 0.9 ± 0.59 mm/year on 2D measurements, and 0.2 ± 0.17 cm3/year on volumetric measurements, with a relative shrinkage of 40 ± 16.9%. Two remarkable radiologic features were observed: First, a festooned aspect, defined by multiple curves in the tumor outline, noticed in 12 cases (86%); second, the appearance of cerebrospinal fluid filling the internal auditory meatus, associated with an enlargement of the internal auditory meatus compared to the contralateral side, and observed in 10 out of 13 cases with internal auditory meatus invasion (77%). Those two aspects were associated in 64% of cases. CONCLUSION: These two newly reported radiologic features could help neurosurgeons, oto-neurosurgeons and neuroradiologists to identify a spontaneous vestibular schwannoma involution at first visit. This could allow any treatment to be postponed, monitoring to be more widely spaced, and patients to be reassured.

Spontaneous Regression of Recurrent Undifferentiated Carcinoma of the Endometrium.

We herein report a very rare case of spontaneous regression of recurrent undifferentiated carcinoma of the endometrium. An 80-year-old woman had undergone total hysterectomy with bilateral adnexectomy for undifferentiated carcinoma of the endometrium. The cancer recurred locally 10 months after surgery and then metastasized to the lung and liver. After she and her family elected to receive supportive care without active treatment, the local recurrences dramatically decreased, and the metastases of the lung, liver, and peritoneum also disappeared. This case showed that spontaneous regression can occur even with malignant tumors showing an extremely poor prognosis, such as undifferentiated carcinoma of the endometrium.

Watch and See Strategy in Selected Neuroblastoma Case Scenarios: Success and Limitations.

Neuroblastoma (NBL) in infants has the potential to regress/mature spontaneously. The literature showed some cases, subjected to initial observation, with reasonable outcome. Deferring/avoiding active treatment was investigated in selected favorable NBL cases. Patients enrolled on the watch and see strategy (W&S) had small primary tumor, localized stages 1 to 2, uncomplicated stage 4s, or stage 3. Tissue biopsy was not mandatory for infants below 6 months with localized mass. On progression, active intervention was indicated according to disease stage and risk after biological characterization. In total, 32 patients were enrolled on W&S strategy; male/female:2.6/1. Twelve had stages 1 to 2, 16 had stage 4s, and 4 were stage 3. Primary adrenal site was reported in 85% patients, and 65% patients had small mass (≤5 cm). Five-year overall and event-free survival were 100% and 80.9±7%, respectively, with a 43-month median follow-up duration. Spontaneous total/near total resolution of mass occurred in 50% patients. Median time to regression was 1.7 months, and 20.7 months until resolution. Only 19% patients witnessed progression; median time to progression was 4.8 months. W&S is a reasonable approach for localized and uncomplicated stages 3 and 4S NBL. Extended tumor size is a newly investigated entity in the present study. All progressive cases were safely rescued with 100% survival outcome.

Immunohistochemical Evidence of the Involvement of Natural Killer (CD161+) Cells in Spontaneous Regression of Lewis Rat Sarcoma.

BACKGROUND/AIM: Spontaneous regression (SR) of tumours is a rare phenomenon not yet fully understood. The aim of this study was to investigate immune cells infiltrating progressive and SR tumours in a Lewis rat sarcoma model. MATERIALS AND METHODS: Rats were subcutaneously inoculated with rat sarcoma R5-28 (clone C4) cells. Developing tumours were obtained on day 42 and cryosections were immunohistochemically processed for detection of immune cells. RESULTS: A high density of granulocytes was found in the necrotic areas of both progressive and SR tumours. CD4+ cells and CD8+ cells were rare and sparsely dispersed in the tumour tissue without clear difference between the two types of tumours. On the contrary, CD161+ cells were abundant and evenly distributed in SR tumours, but these cells were very rare in progressive tumours. CONCLUSION: Based on the differences in number and distribution of the immune cell subpopulations, we believe that natural killer (CD161+) cells play a major role in the destruction of cancer cells during SR of tumours in this Lewis rat model.