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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

Author–year

Age/sex

Primary site

Remission site

Proposed mechanisms

Follow-up

Wyeth et al., 18974

42/F

Shoulder

Shoulder and axilla

Mixed bacterial toxins

Not reported

Watson, 19025

39/F

Back

Back

Not reported

Not reported

Shore, 19366

6 months/F

Interscapular region

Interscapular region

Not reported

7 years

Coley et al., 19277

27/M

Left tibia

Left tibia

Mixed bacterial toxins

37 years

Penner, 19538

2 months/M

Lower thigh

Lower thigh

Not reported

5 years

Dobson et al., 19569

5 months/F

Thigh, lower abdomen

Thigh, lower abdomen

Not reported

12 years

Levin, 195710

29/F

Humerus

Humerus

Not reported

4 years

Cole et al., 195911

5/M

Right fibula

Right fibula

Not reported

6 years

Berner et al., 196512

Newborn/F

Head, face, neck

Head, face, neck

Not reported

3 years

Tietjen et al., 197413

60/F

Stomach

Stomach and adjacent mesocolon

Not reported

3 years

Nauts, 197514

29/F

Gluteal region and thigh

Gluteal region and thigh

Mixed bacterial toxins

47 years

Meares, 197815

25/M

Femur

Ribs, sternum, crest of ilium, lungs

Immune response

Not reported

Dissinc et al., 197816

36/M

Pelvis

Pelvis

Immunological factors

Not reported

Jenkins et al., 198617

15/F

Buttock and pelvis

Buttock, thigh, and calf

Not reported

10 years

Casado et al., 198818

77/M

Penis

Glans penis and prepuce

Not reported

1.5 years

Miura et al., 200219

4/M

Right hand

Right hand

Apoptosis or immune maturation

4 years

Ota et al., 200220

58/F

Uterus

Lungs

Immunological and hormonal factors

5 years

Otrock et al., 200621

75/F

Liver

Liver and lungs

Not reported

20 months

BaniHani et al., 200922

38/M

Abdomen

Abdomen, lungs, heart

Immunologic response

Not reported

Matsuo et al., 200923

57/F

Proximal thigh

Proximal thigh

T-lymphocyte–mediated immune response

2 years 2 months

Bacci et al., 200824

19/M

Right thigh

Lungs

Metastasis suppressor genes

Not reported

Kim, 200825

72/F

Breast

Lungs and scalp

Not reported

1 year

Zhao et al., 201426

49/M

Peritoneum

Peritoneum

Not reported

Not reported

Zhao et al., 201426

59/M

Stomach and pancreas

Stomach and pancreas

Not reported

1 year

Kinoshita et al., 201527

25/F

Inguinal region

Lungs and inguinal region

Immune response post-biopsy

Not reported

Lourenco et al., 201228

14/M

Tongue

Cr at 5 years

Chang, 200029

57/M

Lower esophagus

Esophageal junction

None reported

9 years

Chang, 200029

53/M

Right hepatic lobe

None reported

17 years

Rohdenburg, 191830

Bacterial toxin injections

Nauts et al., 194631

Toxin therapy

De et al., 201132

22/F

Retroperitoneal space

Kondo et al., 200033

78/F

Feet and legs

Skin lesions

CD8 cell infiltration

6 months

Nagy et al., 200034

53/M

Pretibial region, left arm, pharynx, right conjunctiva

Restored immune function

2 months

Leven, 195735

29/F

Left shoulder and left arm

Left arm

Complete healing by Jan. 1955

Hosahalli & Asanna et al., 202336

1/M

Skin

Left cheek and scalp

KAT6A::EP300 fusion

24 months

Macías-García, 201837

83/F

Blood vessels

None reported

Several weeks postbiopsy

Medici, 202438

77/M

Lymph nodes and muscles

Retroperitoneal lesion and lymph nodes

Immune response due to infection

1 year with reduction in size

Campos & Amírez et al., 202439

58/F

Lung

Metastatic lesions

Immune system activation

9 months

Mizuno, 201940

62/M

Skin

Skin

Immune response

34 days

Sait, 201841

5/M

Muscle

Benign clinical course in early diagnosis

19 months

Silvia & Unior et al., 202442

35/F

Skull and spine

Skull base lesion

Exacerbated immune response

5 months

Dissing et al., 197843

36/M

Alive at 6 years

Kauffman & Stout et al., 196544

Cook, 196645

Nodule

Complete spontaneous regression

Bart & Kopf et al., 198246

62/M

Lesions

Several years

Bluming, 197647

Occasional spontaneous regression

Pilgrim, 198848

40/M

Kaposi sarcomas

Reduction of immunosuppression

Complete regression within 3 months

Perrin et al., 198849

34/M

Janier et al., 198550

25/M

Lesions

Levy et al., 198551

Psychological makeup

Surviving as well as treated patients

Real & Krown et al., 198552

Blayney et al., 198653

51/M

Steroid withdrawal

Complete remission by April 1985

References:

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  33. Kondo, Y., Izumi, T., Yanagawa, T., Kanda, H., Katano, H., & Sata, T. (2000). spontaneously regressed Kaposi's sarcoma and human herpesvirus 8 infection in a human immunodeficiency virus-negative patient. Pathology international, 50(4), 340–346. https://doi.org/10.1046/j.1440-1827.2000.01043.x
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  49. Perrin et al., 1988. Reversal of Positive Serology for Human Immunodeficiency Virus (HIV); Observation of Two Cases. Schweizerische Medizinische Wochenschrift 118(45): Nov 12 1988; 1641-1644
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