Sarcoma
Sarcoma
Epidemiology:
Sarcoma is a rare and diverse group of malignant neoplasms arising from mesenchymal tissues, characterized by significant variability in clinical behavior and prognosis. The annual incidence of sarcomas in the United States is approximately 3.4 cases per 100,000 people, underscoring their relative rarity among cancers1. Within this spectrum, spontaneous remission (SR) remains an exceptionally uncommon phenomenon, with reported cases constituting minimally 1% of total sarcoma occurrences, thereby complicating prevalence estimates due to underreporting of less dramatic cases2. SR generally remains enigmatic, with unclear mechanisms such as immune response activation or localized ischemia being hypothesized as potential catalysts for these rare cases 3.
Clinical Characteristics:
To date, there have been twenty-five reported cases of SR involving various sarcomas. Several clinical patterns can be identified among these cases. The patients’ ages at the time of regression ranged from newborn to 77 years, with a slight predominance in females. Primary tumor sites varied widely, including the limbs, trunk, abdomen, pelvis, and visceral organs such as the stomach, uterus, liver, and lungs. In most cases, remission occurred locally at the primary site, although several involved distant or multiple sites such as the lungs, lymph nodes, or heart. See Table 1 below for further information.
Histological Characteristics:
Of the cases analyzed, the histological types primarily included soft tissue and bone sarcomas, with occasional reports involving visceral or rare primary sites such as the stomach, liver, uterus, and lung. Cases representing benign or non-malignant lesions were excluded to ensure focus on confirmed malignant spontaneous regression events. This collection encompasses both pediatric and adult presentations, reflecting the broad clinical spectrum of sarcoma regression phenomena documented over more than a century.
Proposed Contributing Mechanisms:
Among the reported cases, the proposed mechanisms of spontaneous regression varied notably. In three patients, regression was associated with exposure to mixed bacterial toxins, suggesting an infection-induced immune response. One case attributed regression to biopsy-induced immune activation, while others implicated T-lymphocyte–mediated or hormonal factors. The remaining cases did not report a specific cause of regression. Collectively, these observations suggest that infection, immune stimulation, and hormonal influences may each contribute to the spontaneous regression of sarcomas.
Site and Extent of Remission:
Among the reported cases, complete tumor regression was observed in nearly all patients, with remission occurring at both primary and metastatic sites. Most cases demonstrated regression confined to the primary sarcoma lesion, while several also showed resolution of metastatic involvement, particularly in the lungs and regional tissues. The duration of follow-up ranged from several months to over four decades, with some patients maintaining long-term remission for up to 47 years. Although follow-up information was not consistently reported, these findings suggest that spontaneous regression in sarcomas can, in certain instances, lead to durable disease control, distinguishing it from the transient regressions occasionally seen in other malignancies.
Table 1: Sarcoma SR Cases and Clinical Characteristics
Age/sex | Primary site | Remission site | Proposed mechanisms | Follow-up | |
|---|---|---|---|---|---|
42/F | Shoulder | Shoulder and axilla | Mixed bacterial toxins | Not reported | |
39/F | Back | Back | Not reported | Not reported | |
6 months/F | Interscapular region | Interscapular region | Not reported | 7 years | |
27/M | Left tibia | Left tibia | Mixed bacterial toxins | 37 years | |
2 months/M | Lower thigh | Lower thigh | Not reported | 5 years | |
5 months/F | Thigh, lower abdomen | Thigh, lower abdomen | Not reported | 12 years | |
29/F | Humerus | Humerus | Not reported | 4 years | |
5/M | Right fibula | Right fibula | Not reported | 6 years | |
Newborn/F | Head, face, neck | Head, face, neck | Not reported | 3 years | |
60/F | Stomach | Stomach and adjacent mesocolon | Not reported | 3 years | |
29/F | Gluteal region and thigh | Gluteal region and thigh | Mixed bacterial toxins | 47 years | |
25/M | Femur | Ribs, sternum, crest of ilium, lungs | Immune response | Not reported | |
36/M | Pelvis | Pelvis | Immunological factors | Not reported | |
15/F | Buttock and pelvis | Buttock, thigh, and calf | Not reported | 10 years | |
77/M | Penis | Glans penis and prepuce | Not reported | 1.5 years | |
4/M | Right hand | Right hand | Apoptosis or immune maturation | 4 years | |
58/F | Uterus | Lungs | Immunological and hormonal factors | 5 years | |
75/F | Liver | Liver and lungs | Not reported | 20 months | |
38/M | Abdomen | Abdomen, lungs, heart | Immunologic response | Not reported | |
57/F | Proximal thigh | Proximal thigh | T-lymphocyte–mediated immune response | 2 years 2 months | |
19/M | Right thigh | Lungs | Metastasis suppressor genes | Not reported | |
72/F | Breast | Lungs and scalp | Not reported | 1 year | |
49/M | Peritoneum | Peritoneum | Not reported | Not reported | |
59/M | Stomach and pancreas | Stomach and pancreas | Not reported | 1 year | |
25/F | Inguinal region | Lungs and inguinal region | Immune response post-biopsy | Not reported | |
14 -year-old male. | Tongue, dorsal aspect | Cr at 5 years followup | None reported | Cr at 5 years followup | |
A) 57-year old Japanese male who had near total gastrectomy, omentectomy, splenectomy, resection of distal 1/3 of pancreas, jejunojejunostomy, and feeding jejunostomy for adenocarcinoma of stomach | A) lower esophagus, 2-3 cm above esophagogastric junction | A) endoscopy one week after diagnosis of recurrent esophageal cancer showed only severe inflammation at esophageal junction; repeated endoscopies over the next 9 years showed no recurrent squamous cell carcinoma | A) None reported | A) endoscopy one week after diagnosis of recurrent esophageal cancer showed only severe inflammation at esophageal junction; repeated endoscopies over the next 9 years showed no recurrent squamous cell carcinoma | |
B) 53-year old Chinese man from Tahiti presented with large mass in upper right abdomen; history of Billroth II gastrectomy for large benign gastric ulcer and cirrhosis of the liver in August of 1966 | B) right hepatic lope | B) 17 years after surgery, patient was examined and shown free of cancer | B) None reported | B) 17 years after surgery, patient was examined and shown free of cancer | |
The observation that a neoplasm may be absorbed subsequent to, or during, an acute infection, opens a most interesting field for speculation. The greater number of cases in this group have occurred after an attack of erysipelas, an observation which has led to the use of toxins of the causative organism as a therapeutic measure. However, further observation shows that recession has also occurred after smallpox, pneumonia, malaria, and acute tuberculosis. No one organism is, therefore, specific in causing regression. In the histories of those cases that are given in detail, there is a common symptom, namely, high temperature, sustained without remission for several days. | Injections of bacterial toxins, while they do give rise to violent febrile reactions, are not characterized by the continuance of fever in full violence and without remission over a period of forty-eight hours. | The observation that a neoplasm may be absorbed subsequent to, or during, an acute infection, opens a most interesting field for speculation. The greater number of cases in this group have occurred after an attack of erysipelas, an observation which has led to the use of toxins of the causative organism as a therapeutic measure. However, further observation shows that recession has also occurred after smallpox, pneumonia, malaria, and acute tuberculosis. No one organism is, therefore, specific in causing regression. In the histories of those cases that are given in detail, there is a common symptom, namely, high temperature, sustained without remission for several days. | |||
the majority of spontaneous regressions recorded in the literature occurred during or following an acute bacterial infection of some sort | toxin therapy | the majority of spontaneous regressions recorded in the literature occurred during or following an acute bacterial infection of some sort | |||
22 years old woman, had given birth six months prior | Retroperitoneal space | After laparotomy, no tumor was found. | After laparotomy, no tumor was found. | ||
78-year-old female Native to Okinawa, Japan-- endemic to Kaposi's sarcoma | Kaposi's sarcoma developing in the feet and legs | Skin biopsies revealed complete regression of skin lesions 8 months later No recurrence observed in following 6 months | Evidence of numerous CD8 cell infiltration in second biospy tissues | Skin biopsies revealed complete regression of skin lesions 8 months later No recurrence observed in following 6 months | |
53-year-old Caucasion male with end-stage renal disease | Pretibial region on legs, left arm, mucuous membranes of pharynx, and right conjunctive, diagnosed as Kaposi's sarcoma | 2 months after grafectomy and hemodialysis and upon discontinuation of immunosuppressive therapy, repeat biopsy confirmed disappearance of KS lesions almost completely HHV8 viral DNA still detected | With restored immune function, HHV8 can be suppressed into latency | 2 months after grafectomy and hemodialysis and upon discontinuation of immunosuppressive therapy, repeat biopsy confirmed disappearance of KS lesions almost completely HHV8 viral DNA still detected | |
29-year-old female | Left shoulder and left arm | Experienced subsiding of pain in arm after findings of periosteal proliferation Cast removed in Oct. 1952 Roentgenogram in Jan. 1955 demonstrated complete healing of humerus, except for slight deformity & sclerosis | Mechanism is unknown | Experienced subsiding of pain in arm after findings of periosteal proliferation Cast removed in Oct. 1952 Roentgenogram in Jan. 1955 demonstrated complete healing of humerus, except for slight deformity & sclerosis | |
17-year-old boy | bones | Progressive ossification of the lesion was further confirmed at the 2-year follow-up. This reduction of lesions was visible on all affected bones. Some locations had almost disappeared at the 2-year fol- low-up, especially in the pelvic ring | none reported | Progressive ossification of the lesion was further confirmed at the 2-year follow-up. This reduction of lesions was visible on all affected bones. Some locations had almost disappeared at the 2-year fol- low-up, especially in the pelvic ring | |
newborn boy | skin | Subcutaneous nodules reduced in size and became undetectable, and some of them tended to turn into dermal nodules which appeared at the body surface and then disappeared. CT at eight months demonstrated that most visceral lesions were undetectable | None reported | Subcutaneous nodules reduced in size and became undetectable, and some of them tended to turn into dermal nodules which appeared at the body surface and then disappeared. CT at eight months demonstrated that most visceral lesions were undetectable | |
83-year-old woman. history of dyslipidemia, untreated meningioma and joint disorder of unknown origin | blood vessels | Several weeks postbiopsy, the neoplasm had undergone complete clinical regression | None reported | Several weeks postbiopsy, the neoplasm had undergone complete clinical regression | |
24-year-old male | ureter | Sonography after three months showed a reduction in size to 9.4 × 5.4 cm2. 1 year after diagnosis, an MRI showed regression of the tumor with a small resi- due of 2.2 × 1.2 × 1.9 cm2 along the right ureter and a minimal hydronephrosis of the right kidney without loss of renal function. A second MRI 6 months later and a third MRI 1 year later showed persisted regression without hydronephrosis | None reported | Sonography after three months showed a reduction in size to 9.4 × 5.4 cm2. 1 year after diagnosis, an MRI showed regression of the tumor with a small resi- due of 2.2 × 1.2 × 1.9 cm2 along the right ureter and a minimal hydronephrosis of the right kidney without loss of renal function. A second MRI 6 months later and a third MRI 1 year later showed persisted regression without hydronephrosis | |
77-year-old man. History of hypertension, dyslipidemia, benign prostatic hyperplasia, and previous inguinal hernioplasty. | lymph nodes, muscles | Subsequently, a progressive reduction in the diameters was found, despite the patient did not undergo specific treatments. After a first observation period of approximately 1 year with quarterly CT scans, the diameters of the retroperitoneal lesion were reduced up to 6 × 15 × 34 mm, and the lymphadenopathies near the left kidney shrank to a size of 17 × 11 mm and 13 × 7 mm, respectively. | there was an underlying infectious event at the tumor site, as purulent material was drained. This probably initiated a major immune response against inflammatory pseudotumor (IPT), thus leading to a progressive decrease in the size of the tumor mass. | Subsequently, a progressive reduction in the diameters was found, despite the patient did not undergo specific treatments. After a first observation period of approximately 1 year with quarterly CT scans, the diameters of the retroperitoneal lesion were reduced up to 6 × 15 × 34 mm, and the lymphadenopathies near the left kidney shrank to a size of 17 × 11 mm and 13 × 7 mm, respectively. | |
58-year-old woman | lung | At first, one month after RT, it increased in size to be followed by a reduction of the mass (9 months after). This reduction was observed in all the metastatic lesions, even in those that were not irradiated. | Radiotherapy led to immune system activation within the micro-tumoral environment. | At first, one month after RT, it increased in size to be followed by a reduction of the mass (9 months after). This reduction was observed in all the metastatic lesions, even in those that were not irradiated. | |
62-year-old man | skin | repeat MRI 21 days after biopsy showed a significant decrease in size. At the time of the surgery 34 days after the open biopsy, the tumor has regressed even further where it was difficult to palpate the mass. | open biopsy activates host immune response | repeat MRI 21 days after biopsy showed a significant decrease in size. At the time of the surgery 34 days after the open biopsy, the tumor has regressed even further where it was difficult to palpate the mass. | |
5-month-old infant | muscle | Four months following diagnosis, the mass appeared to be decreasing in size following the biopsy. 6 weeks later, MRI showed that the tumor was stable in size and now appeared more cystic and necrotic. The tumor started to shrink thereafter and by the age of 24 months, was impalpable | in patients diagnosed with IFS during the first 6 months of life, a more benign clinical course is possible | Four months following diagnosis, the mass appeared to be decreasing in size following the biopsy. 6 weeks later, MRI showed that the tumor was stable in size and now appeared more cystic and necrotic. The tumor started to shrink thereafter and by the age of 24 months, was impalpable | |
35-year-old woman | skull, spine | 5 months after the COVID-19 infection, another MRI was performed to re-evaluate the tumor and define the surgical plan. A surprising regression of the tumor was noticed. A 1 cm × 0.6 cm × 0.5 cm lesion was restricted to the left side of the skull base, no extraosseous component was identified, and there was no mass effect over the brainstem, cervical spinal cord, or even longus colli muscles | the onset of COVID-19 with exacerbated immune response and improvement in anti-tumor immunity (detection and elimination), by both direct and cross-reactions, had a fundamental role in this surprising chordoma regression | 5 months after the COVID-19 infection, another MRI was performed to re-evaluate the tumor and define the surgical plan. A surprising regression of the tumor was noticed. A 1 cm × 0.6 cm × 0.5 cm lesion was restricted to the left side of the skull base, no extraosseous component was identified, and there was no mass effect over the brainstem, cervical spinal cord, or even longus colli muscles | |
70-year-old man | S4, S5 vertebrae, coccyx | A notable spontaneous decrease in tumor size was identified on the subsequent MRI 4 weeks after the first one. | None reported | A notable spontaneous decrease in tumor size was identified on the subsequent MRI 4 weeks after the first one. | |
75-year-old woman. history of hypertension, mitral valve prolapse, history of head trauma with a seizure disorder (controlled on medications), and a contrast allergy. She was taking multiple medications for her chronic medical conditions, including gabapentin, famotidine, loratadine, hydralazine, atenolol, a nitroglycerin patch, and vitamins B2, B6, and B12. Also, intermittently and inconsistently been taking a number of alternative supplements since diagnosis, including “Healthy aging Anti-oxidant complex” (containing Resevatrol, R-alpha lipoic Acid, hyaluronic acid, Astaxanthin, Acai), Echinacea, and Russian supplements including Badger (meles meles Linnaeus) fat/oil tablets and Sea buckhorn (Hippophae rhamnoides) oil. | skull | On repeat pre-operative MRI without contrast, she was found to have had 61.7% regression of her skull base mass. | The chordoma may have regressed from an autoimmune reaction | On repeat pre-operative MRI without contrast, she was found to have had 61.7% regression of her skull base mass. | |
36-year-old man | Clinical and radiological condition improved spontaneously, patient is alive, almost symptom-free, after 6 years of follow-up, pain decreased, and during the following years the complaints gradually disappeared, patient has been free of pain, and he walks almost normally, radiological remission took place, the tumour area became increasingly delimited and sclerosed | Clinical and radiological condition improved spontaneously, patient is alive, almost symptom-free, after 6 years of follow-up, pain decreased, and during the following years the complaints gradually disappeared, patient has been free of pain, and he walks almost normally, radiological remission took place, the tumour area became increasingly delimited and sclerosed | |||
Chinese female, first seen at the age of seven | marked regression in the tumor since 1943, tumor is slowly becoming smaller, no ulceration | onset of menstruation, ovarian function | marked regression in the tumor since 1943, tumor is slowly becoming smaller, no ulceration | ||
Female, 40 years, nulliparous | the tumour had gradually decreased in size and had wholly disappeared after two years | the tumour had gradually decreased in size and had wholly disappeared after two years | |||
nodule becomes pale and wrinkled, and gradually disappears, leaving an inconspicuous scar. Complete spontaneous regression does occur | nodule becomes pale and wrinkled, and gradually disappears, leaving an inconspicuous scar. Complete spontaneous regression does occur | ||||
62-year-old Jewish diabetic white man | lesions disappeared completely without treatment, remained free of lesions for several years, entire lesion disappeared spontaneously | lesions disappeared completely without treatment, remained free of lesions for several years, entire lesion disappeared spontaneously | |||
A Turkish teacher, 40 years old, had been dependent on dialysis since March 1981 because of terminal kidney insufficiency with suspected chronic glomerulonephritis. On June 9, 1984, he received a kidney transplant in the Transplant Center Erlangen-Nuernberg. | After a few weeks the Kaposi sarcomas were reduced in size and regressed completely within 3 months after reduction of the immunosuppressive therapy. | Reduction of immunosuppression | After a few weeks the Kaposi sarcomas were reduced in size and regressed completely within 3 months after reduction of the immunosuppressive therapy. | ||
The second observation is that of a single 34-year-old male in good health who reportedly engaged in bisexual behavior, and who spends several months a year in tropical regions. His medical history did not reveal other risk factors. | The serologic data of successive serum samples collected from these persons were first negative, then positive (including antibodies directed against Gag and Env gene products), and finally negative for presence of anti-HIV-I antibod-ies. | The serologic data of successive serum samples collected from these persons were first negative, then positive (including antibodies directed against Gag and Env gene products), and finally negative for presence of anti-HIV-I antibod-ies. | |||
25-year-old homosexual man | Some of the lesions disappeared spontaneously after Stage 1 or 2: the others disappeared after Stage 3. | Some of the lesions disappeared spontaneously after Stage 1 or 2: the others disappeared after Stage 3. | |||
10 men who have chosen not to enter conventional treatment protocols | surviving at least as well as patients who have been treated | strong, independent psychological makeup | surviving at least as well as patients who have been treated | ||
Spontaneous regression | Spontaneous regression | ||||
51-year-old white male homosexual, sexually active with multiple sexual partners, no previous medical illness, no previous sexually transmitted diseases | Two months later, gradual regression of the lesions was noted, which was complete by April 1985 | The KS resolved when the steroids were withdrawn | Two months later, gradual regression of the lesions was noted, which was complete by April 1985 | ||
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