Spontaneous Regression Accompanied by Concomitant Immune Alterations in a Patient with Chronic Lymphocytic Leukemia.

Spontaneous regression (SR) of chronic lymphocytic leukemia (CLL) is a rare event (0.2% - 1%). Some advances have been made in understanding the tumor genetic characteristics of such patients, although the immunological mechanisms leading to SR remain unclear. We describe a series of immunological events related to regression dynamics, allowing the identification of a SR phase (associated with >99% reduction of CLL cells in peripheral blood and adenopathy resolution in less than one year, concurrently with a nine-fold increase in monocyte counts, high B2M and the appearance of an oligoclonal serum IgG band), followed by a persistent regression (PR) phase that was maintained for ≥17 months. Our observations highlight a role of monocytes and B2M in SR, potentially related to immune activation. The oligoclonal IgG band detected during SR was maintained in PR, suggesting either a change in the ability of malignant cells (IgM+IgD+IgG‒) to differentiate into IgG-secreting cells, or an anti-tumor humoral response from normal B cells. These findings imply immune and molecular mechanisms required to eliminate malignant cells and might suggest new immunotherapies for CLL.

Spontaneous regression of an interhemispheric arachnoid cyst: illustrative case.

BACKGROUND: Intracranial arachnoid cysts are benign collections of cerebrospinal fluid that are often asymptomatic and discovered incidentally. An interhemispheric location of these lesions is rare, with only a few such cases reported in the literature. Though spontaneous regression of arachnoid cysts has been described in other locations, to date this phenomenon has not been reported in interhemispheric fissure cysts. OBSERVATIONS: In this report, we describe a patient with a large, multiloculated interhemispheric arachnoid cyst diagnosed on prenatal ultrasound. She did not exhibit neurologic deficits or signs of increased intracranial pressure and was observed with serial imaging. After several years of observation, imaging revealed spontaneous and progressive decrease in the cyst size. LESSONS: We illustrate a case of regression of an interhemispheric arachnoid cyst in a pediatric patient. To our knowledge, this is the first reported case of spontaneous shrinkage of an arachnoid cyst in this location. Although the current presentation is rare, this reporting adds to the current understanding of natural history of arachnoid cysts and provides an example of radiographical improvement without intervention of a cyst located within the interhemispheric fissure.

Sacrococcygeal chordoma with spontaneous regression due to a large hemorrhagic component.

Chordoma is a malignant bone tumor originating from notochordal remnants, most commonly occurring at the sacrococcygeal junction. We present a case of a 70-year-old male with chronic pain in the lower lumbar spine. MRI performed elsewhere revealed a large tumor that involved S4, S5, and the coccyx with a presacral soft tissue component. The lesion was heterogeneously hyperintense on T2-weighted images with a thick hypointense rim anteriorly. On T1-weighted images, the lesion showed a native hyperintense signal centrally probably due to hemorrhage. Based on this MRI, the diagnosis of chordoma was suggested. A spontaneous marked reduction in size was observed on a 4-week interval MRI performed at our institution before biopsy. Due to spontaneous tumor shrinkage along with peripheral enhancement, a differential diagnosis of infection or bleeding in a retrorectal cyst was proposed. This case teaches us that chordomas may contain a large hemorrhagic component, which is hyperintense on T1-weighted images and shows peripheral rim enhancement. Spontaneous shrinkage of a tumor may occur due to the resolution of a hematoma within weeks. Biopsy is key to obtain the correct diagnosis. Understanding the typical and more rare features of chordomas is key for MSK radiologists as well as pathologists. Chordomas are typically slow-growing tumors, but radiologists should be aware that intratumoral hemorrhage can lead to rapid changes in tumor size, which may be mistaken for either regression or progression of tumor. This case highlights the importance of considering hemorrhagic events within chordomas in the differential diagnosis when observing size fluctuations on imaging.

A rare and challenging case of extrahepatic costal metastases from an unknown primary hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) typically presents with a primary hepatic mass. Nevertheless, on rare occasions, the initial presentation can be exclusively related to extrahepatic metastases and the most common sites of metastases are the lungs, lymph nodes, bones, and adrenal glands. While, bone metastases are generally accompanied by multiple metastatic spreads elsewhere in the body or previously diagnosed HCC, cases of solitary bone metastases with no liver lesion at imaging have been reported. Indeed, two rare entities of HCC have been reported in the literature which are the ectopic hepatocellular carcinoma and the infiltrative type of hepatocellular carcinoma with a very challenging radiologic diagnosis and poor prognosis. In this article, we present a case of extrahepatic costal metastases of hepatocellular carcinoma, which was diagnosed through a bone biopsy, with no focal lesion on liver imaging including ultrasound, multiphase MRI, and CT scan except for the presence of a portal vein thrombosis. It is important to consider the possibility of HCC metastases when evaluating rapidly growing extrahepatic lesions in patients with chronic liver disease and to consider the tumor characteristics and imaging findings as well as limitations to make accurate and timely diagnosis leading to improved patient management. Our patient had probably an infiltrating HCC because of two prominent factors: the presence of portal vein thrombosis and a markedly elevated alpha-fetoprotein (AFP). A liver biopsy was crucial in order to confirm the diagnosis but unfortunately it could not be performed because of the unexpected death of the patient due to hemorrhagic shock. It is also worth noting in this case, that the elevated level of AFP raised the suspicion on an underlying HCC and contributed to more elaborate diagnostic tests.

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.

Spontaneous Regression of Epstein-Barr Virus-Positive Diffuse Large B-cell Lymphoma in an HIV-Positive Patient: A Case Report and Literature Review.

Individuals infected with human immunodeficiency virus (HIV) have a greater risk of developing malignancies, including both acquired immunodeficiency syndrome (AIDS)-defining malignancies as well as many non-AIDS-defining cancers. Several factors contribute to the increased incidence of malignancies in this population such as the direct effects of HIV itself, immune deficiency, co-infection with oncogenic viruses, environmental factors, and the effects of combination antiretroviral therapy (cART). The improvement of the immune response following the introduction of cART results in a better response to conventional therapies for malignancies, including chemotherapy, radiotherapy, and surgery. Significant disparities still exist in cancer treatment for people living with HIV and afflicted with cancers compared to those without HIV, with many in the former group not receiving any cancer treatment at all. We report a rare case whereby a newly diagnosed HIV-infected patient with Epstein-Barr virus-positive diffuse large B-cell lymphoma showed spontaneous regression of the lymphoma with the introduction of cART alone without any treatment of the cancer itself. We reviewed similar cases described in the literature and examined the possible explanations for this phenomenon.

Thymoma Exhibiting Spontaneous Regression With Cystic Change Due to Acute Infarction: A Case Report and Literature Review.

Spontaneous regression (SR) of thymoma is rare. We report a case of a surgically resected thymoma due to cystic changes owing to acute ischemic infarction with an increased anti-acetylcholine receptor antibody level. A 61-year-old male underwent a computed tomography (CT) scan, which showed a 4.9 cm anterior mediastinal tumor and slight right pleural effusion. Blood test results indicated an elevated white blood cell count of 13300/mL. One month later, an enhanced CT scan at our hospital showed spontaneous mediastinal tumor regression to 3.7 cm and no pleural effusion. The tumor contained homogeneous low-density areas on enhanced CT, which showed high intensity on T2-weighted magnetic resonance imaging, indicating cystic changes. He had no symptoms of myasthenia; however, his anti-acetylcholine receptor antibody level was slightly elevated (0.4 nmol/L). Suspecting a thymoma, an extended total thymectomy through a median sternotomy was performed. Histopathological analysis confirmed the diagnosis of thymoma type B2 and Masaoka stage I. SR is due to acute intratumoral infarction. At two years postoperatively, no tumor recurrence or development of myasthenia gravis was observed. Thymomas should be included in the differential diagnosis of anterior mediastinal tumors that regress spontaneously with cystic changes, pleural effusion, and an elevated inflammatory response. Mature cystic teratoma rupture should be differentiated, but preoperative biopsy is often challenging owing to necrotic and fibrous tissues; therefore, early surgical resection is required for diagnosis and treatment.

Genome Sequencing of Multiple Primary Lung Cancers Harbouring Mixed Histology and Spontaneously Regressing Small-Cell Lung Cancer.

Up to 15% of lung cancer patients present two or more anatomically separate primary lung lesions, known as multiple primary lung cancers (MPLCs). While surgical resection or stereotactic body radiation therapy (SBRT) is the standard of care for most early-stage lung cancer cases, this may not be an option for patients with widespread tumours, highlighting the need for the improved targeted management of MPLC patients, which remains challenging. Moreover, the spontaneous regression (SR) of small-cell lung cancer (SCLC) is rare, with only four cases accounted for between 1988 and 2018. We report a rare MPLC case harbouring the mixed histology of non-small-cell lung cancer adenocarcinoma (NSCLCa) and SCLC and the SR of SCLC without treatment. The patient was diagnosed in 2015 with MPLCs, identified as NSCLCa and SCLC. In 2016, a restaging PET/CT scan prior to the start of treatment showed SCLC SR. In 2018, a further tumour was detected in the patient's mandible, and a re-biopsy of the SCLC revealed histology consistent with NSCLCa. Whole-genome sequencing (WGS) analysis identified a high expression of programmed death ligand-1 (PDL-1) in the NSCLCa, which was treated with pembrolizumab. WGS revealed distinct genomic profiles and mutational mechanisms in MPLCs, suggesting the need for distinct targeted therapies to improve the management of MPLC patients and highlighting the importance of precision evaluation.

Analyses of tertiary lymphoid structures observed in cases of Merkel cell carcinoma showing spontaneous regression.

Merkel cell carcinoma (MCC) is a high-grade skin cancer, but spontaneous regression is observed at a markedly higher frequency than in other carcinomas. Although spontaneous regression is a phenomenon that greatly impacts treatment planning, we still cannot predict it. We previously reported on the prognostic impact of the presence or absence of tertiary lymphoid structures (TLS) and of Merkel cell polyomavirus (MCPyV) infection. To learn more about the spontaneous regression of MCC, detailed analyses were performed focusing on spontaneous regression cases. We collected 71 Japanese patients with MCC including 6 cases of spontaneous regression. Samples were analysed by immunostaining, spatial single-cell analysis using PhenoCycler, and RNA sequencing using the next-generation sequencer (NGS). All 6 cases of spontaneous regression were positive for MCPyV. TLS was positive in all 5 cases analysed. Spatial single-cell analyses revealed that PD-L1-positive tumour cells were in close proximity to CD20-positive B cell and CD3-, 4-positive T cells. Gene set enrichment analysis between MCPyV-positive and TLS-positive samples and other samples showed significantly high enrichment of "B-cell-mediated immunity" gene sets in the MCPyV-positive and TLS-positive groups. In conclusion, TLS may play an important role in the spontaneous regression of MCC.

Spontaneous regression of an epidermoid cyst in a pediatric patient-Case report and review of the literature.

Epidermoid cysts are infrequent, benign, slow-growing, space-occupying lesions that account for 0.5-1.8% of primary intracranial tumors. We report the case of a 17-month-old child who presented in 2015 for one episode of pallor associated with hypotonia. Epilepsy was excluded and MRI was recommended. The MRI was performed and there were no focal parenchymal lesions, but it showed an extra-axial ovoid lesion with imaging characteristics consistent with epidermoid cyst. Follow-up MRI at one year was performed and it showed minimal increased in dimensions of the cyst, without changes into the signal of the lesion. Another MRI was performed 7 years after and it showed complete resolution of the cyst. Six months afterwards, another MRI was performed and it confirmed the complete regression of the cyst, without any extra-axial masses reported. The patient did not present any neurological anomalies. No follow-up MRI was recommended afterwards. Spontaneous regression of epidermoid cyst in pediatric population is an extremely rare event, but it should be taken into account when the patient shows no symptoms. This is the third case of spontaneous regression of an epidermoid cyst reported in pediatric patients, and the first one in the temporal region. Careful follow-up and watchful waiting could be an option to surgical treatment in epidermoid cysts.

A very rare case of spontaneous regression of basaloid squamous cell carcinoma of the lung.

Spontaneous regression of non-small cell lung cancer is relatively rare. Here, we present a very rare case of spontaneous regression of lung cancer which occurred in a patient with basaloid squamous cell lung cancer. To the best of our knowledge, this is the first report of such a case. A 76-year old man was referred to our hospital with nodules in the right upper lobe determined by chest computed tomography. The nodules spontaneously regressed during follow-up. Two years later, the tumor had regrown and the patient subsequently underwent surgery. The pathological findings showed basaloid squamous cell carcinoma. Stimulation of the immune system was considered to be the cause of the spontaneous regression and CD-8 positive and CD-4 positive lymphocytes might play an important role.

Spontaneous regression of recurrent pulmonary large cell neuroendocrine carcinoma with alteration of PD-L1 expression after surgical resection: A case report.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive subtype of non-small cell lung cancer with a poor prognosis. Spontaneous regression, that is, partial or complete disappearance of a malignancy without medical intervention, is extremely rare in LCNEC. Herein, we present a case of spontaneous complete regression in a 71-year-old male patient with recurrent LCNEC after surgical resection. The patient was diagnosed with stage IB LCNEC and underwent surgical resection. At 1-year follow-up, chest computed tomography revealed a recurrent lesion next to the stump site and enlargement of lymph nodes 4R and 7; recurrent LCNEC was confirmed. The patient declined chemoradiation therapy. One year after recurrence, the patient experienced severe multifocal necrotizing pneumonia and was treated with antibiotics, resulting in a gradual decrease in the size of the recurrent lesion. Five years after the initial diagnosis, positron emission tomography/computed tomography revealed no hypermetabolic lesions, indicating the spontaneous complete regression of LCNEC.

Spontaneous shrinkage of sporadic vestibular schwannomas: a clinical and radiological analysis.

OBJECTIVE: The natural history of sporadic vestibular schwannoma (VS) is unpredictable, as tumors may or may not grow and can even spontaneously regress. A spontaneous VS shrinkage MRI-based pattern has been proposed with either a scalloped tumor aspect in the cerebellopontine angle or the appearance of a CSF-filled space surrounding the intracanalicular (IC) tumor within an enlarged canal. The authors of this retrospective study aimed to describe the evolution of sporadic VSs with radiological signs of VS regression and to identify prognostic factors for tumor shrinkage. METHODS: All MRI scans obtained during patient follow-up were reviewed for extracanalicular (EC) and IC size and tumor characteristics. Volumetric measurements were performed on the first and last MRI scans. Shrinkage was considered to have occurred if the tumor size had decreased by ≥ 2 mm in its largest diameter and/or if the volume had decreased by ≥ 20%. Audiometric data were also collected. RESULTS: Among 512 patients under observation for sporadic VSs, 66 (13%) had at least one radiological sign of VS regression and 31 of these (6% overall) had confirmed tumor shrinkage. The mean follow-up was 4 ± 2.5 years. One radiological sign was present on initial MRI in 58% of patients and appeared during the follow-up period in the remaining 42%. Two groups were identified: 31 patients (47%) demonstrated progressive tumor regression during follow-up, and tumors in 35 patients (53%) remained stable once signs of regression were identified (assuming a stabilized regression). The prognostic factors for VS regression were as follows: EC VS extension (p = 0.02), cystic lesion (p = 0.002), and central necrosis (p = 0.02). The mean pure-tone average (PTA) was 43 ± 26.2 dB at the time of diagnosis and 53 ± 28.3 dB at the last visit (p < 0.0001). Among patients with an observed tumor shrinkage, ∆PTA was lower if the inner ear signal on the high-resolution T2-weighted image had improved (-3 ± 8.9 dB, n = 11) than if the inner ear signal had not improved (-10 ± 6.9 dB, n = 20) (p = 0.02) between the initial and last MRI scans. CONCLUSIONS: Spontaneous shrinkage of sporadic VSs could be suspected based on two radiological aspects that are indicative of VSs in progressive or stabilized regression and is an additional argument for the conservative management of these tumors. During follow-up, recovery from a reduced to a normal cochlear fluid MRI signal is a good indicator for hearing preservation.

Regressed Non-metastatic Germ Cell Tumour: A Case Report and Literature Review.

Testicular germ cell tumour regression is a rare phenomenon, where the primary testicular tumour spontaneously regresses, typically with metastatic disease at presentation. We present a case of a regressed germ cell tumour (GCT) in a 44-year-old post-pubertal male. Initially treated for suspected infection, the patient's testicular swelling prompted further investigation, leading to a radical orchidectomy that revealed the unusual histomorphologic findings of an entirely necrotic, non-seminomatous GCT consistent with a pure embryonal carcinoma.

Epithelioid Hemangioendothelioma of the Liver Showing Spontaneous Complete Regression after the Cessation of Methotrexate Intake.

A 71-year-old man with slight fever and dull abdominal pain was referred to our hospital. He had been receiving methotrexate (MTX) to treat his rheumatoid arthritis for more than 6 years but stopped taking MTX after admission due to the rapid aggravation of his liver function. Computed tomography (CT) showed multiple liver lesions with late enhancement, highly suggesting them to be cholangiocarcinomas. Tumor marker levels were normal except for a slightly elevated PIVKA-II level, i.e., 45 mAU/mL (range 0-40 mAU/mL). We did a biopsy to the largest lesion and endoscopic biliary drainage to make a definitive diagnosis of the hepatic lesions and treat jaundice, respectively. Pathological study showed round, polygonal, and spindle-shaped epithelial atypical cells growing in a sarcomatoid fashion. Atypical cells were positive for CD31, CD34, vimentin, and TFE3, and some of them had intracellular vacuoles, leading to the diagnosis of epithelioid hemangioendothelioma (EHE) of the liver. The patient got well 4 weeks after the endoscopic biliary drainage. CTs showed marked regression of the EHE lesions 3 months after biliary drainage and complete regression in 12 months. The patient further developed Hodgkin lymphoma in the para-aortic lymph nodes 23 months after the biliary drainage and is now under chemotherapy for the malignant lymphoma. We, however, have not detected any EHE lesions in the liver or distant organs for at least 16 months after the confirmation of complete regression of the EHE lesions. Oncologists should note the spontaneous regression of the EHE and investigate the correlation between MTX cessation and EHE regression.

Spontaneous vanishing of hepatocellular carcinoma: A case report of an extremely rare incident.

One of the very uncommon clinical conditions is the spontaneous remission of tumors, with scarce reports around the world in various types of tumors. Spontaneous remission of hepatocellular carcinoma (HCC) is extremely rare, but it is well documented with a still unclear underlying mechanism. In this case report, we present one of those exceptional incidents of HCC regression with a trial to tackle possible explanations. Our case, which has a history of successfully treated hepatitis C virus, presented with a large infiltrative right lobar mass invading the main portal vein, with markedly elevated alpha fetoprotein (AFP). According to the applied diagnostic and treatment guidelines, the patient was scheduled for conservative management. Although he did not receive any specific treatments for his condition, the mass regressed in size with recanalization of the portal vein and normalization of AFP after 6 months of follow-up and keep the same for the following 3 years. The mechanisms by which spontaneous regression of HCC can occur are still unknown and should be furtherly investigated better to understand the behavior of such aggressive neoplastic disease.

Pathologically confirmed spontaneous regression of small cell lung cancer after computed tomography-guided percutaneous transthoracic needle biopsy followed by surgery.

BACKGROUND: Spontaneous regression of malignant tumors is a rare phenomenon, especially in primary lung cancer. The underlying mechanisms remain unclear, but they may often involve immunological mechanisms. CASE PRESENTATION: In January 2020, a 78-year-old female underwent examination during follow-up of interstitial pneumonia. Chest X-ray and computed tomography (CT) scan revealed a 1.2 × 1.2 cm nodule in the left lower lobe. Based on CT-guided percutaneous transthoracic needle biopsy (PTNB), it was diagnosed as small cell lung cancer (SCLC). Immunohistochemical staining showed that tumor cells were positive for CD56, synaptophysin, and chromogranin A. Twenty-three days after the CT-guided PTNB, repeat CT scan showed that the tumor size regressed to 0.6 × 0.6 cm. The tumor showed positive uptake in fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT. The maximum standardized uptake value of the nodule was 2.24. PET-CT and enhanced magnetic resonance imaging of the brain showed no distant or lymph node metastasis. The patient's preoperative disease was diagnosed as cT1aN0M0, stageIA1, SCLC. In March 2020, she underwent left lower lobectomy and mediastinal lymph node dissection. Pathological examination of the resected specimen showed that the small tumor cells were dense with a high nucleus to cytoplasm ratio, and the morphological diagnosis was small cell carcinoma. The resected tumor size regressed to 0.05 × 0.02 cm, and no lymph node metastasis was observed. Because it was extremely small, immunohistochemical staining could not be conducted. Active fibrosis and inflammation were present around the tumor. Finally, the patient was pathologically diagnosed as SCLC pT1miN0M0, stage IA1. The patient is alive without recurrence 23 months after surgery with no adjuvant therapy. CONCLUSIONS: We present a rare surgical case of pathologically confirmed spontaneous regression of SCLC after CT-guided PTNB. Although spontaneous regression is extremely rare, we should recognize this phenomenon.