Lymphoma - Spontaneous Remission Database

Lymphoma

Epidemiology

Lymphoma ranks among the most significant hematological malignancies worldwide, with an estimated global incidence of approximately 605,000 cases reported annually in 2020.¹ In the United States, the annual incidence of lymphoma is estimated to be about 89,010 new cases, with approximately 21,080 deaths each year, highlighting the substantial public health impact of this disease.² Despite advances in therapies, lymphoma remains a significant contributor to cancer-related mortality across regions.³ The occurrence of spontaneous remission (SR) in lymphoma is remarkably rare, with documented rates often below 2%, and the true incidence may be further obscured due to underreporting and lack of recognition of remissions that are less pronounced.⁴

Clinical Characteristics:

A total of 205 well-documented cases of spontaneous remission (SR) in lymphoma have been reported between 1956 and 2025. The ages of affected individuals ranged from 2 to 94 years (mean ≈ 52.2 years), with a near-equal male-to-female ratio of approximately 1.1:1 and a peak incidence observed in the 60–80-year age group. Overall, SR was documented across a wide age spectrum but occurred more frequently in older adults, with remission most often noted in generalized or disseminated disease rather than localized lesions, involving both nodal and extranodal sites. See table 1 below for further information.

Histological Characteristics:

Patients who experienced spontaneous remission of lymphoma typically presented with lymphadenopathy or extranodal masses confirmed histologically as malignant lymphoid proliferations. Most cases involved advanced or systemic disease, with the lymph nodes, spleen, and bone marrow as the predominant primary sites, and occasional involvement of the skin, gastrointestinal tract, central nervous system, or thyroid. Remission was verified by follow-up biopsies or imaging demonstrating regression or disappearance of lymphoma cells. Nearly all SR cases showed durable clinical stability or long-term remission, far exceeding the expected prognosis for untreated lymphoma.

Proposed Contributing Mechanisms:

Several mechanisms have been proposed to explain spontaneous remission in lymphoma. The most common involve immune activation following bacterial or viral infections, febrile illnesses, or other inflammatory events. Additional contributing factors include biopsy-related immune stimulation, recovery after withdrawal of immunosuppressive or cytotoxic therapy such as methotrexate or cyclosporine, and immune restoration following discontinuation of antiretroviral or other immunomodulatory treatments. A minority of reports suggest cellular processes such as apoptosis, cytokine-mediated tumor inhibition, or radiation-related immune enhancement as potential contributors.

Site and Extent of Remission:

In most reported cases of spontaneous remission in lymphoma, regression occurred within nodal sites, including cervical, axillary, mediastinal, and abdominal lymph nodes. Extranodal remissions were also documented, involving the skin, gastrointestinal tract, central nervous system, thyroid, breast, and other organs. In many patients, remission extended across multiple regions, reflecting systemic disease resolution rather than localized tumor regression. The duration of remission ranged from a few weeks to more than 20 years, with a considerable number of patients maintaining prolonged clinical and radiologic remission in the absence of active treatment.

Table 1: Leukemia SR Cases and Clinical Characteristics

Author–year	Age/sex	Primary site	Remission site	Proposed mechanisms	Follow-up
Anday et al., 1956¹	68/M	Lymph nodes and liver	Lymph nodes and liver	Humoral factors	4 years
Diwani et al., 1960²	2.5/M	Neck	Neck lymph nodes	Not reported	Not reported
Tigerightt et al., 1962³	43/M	Mediastinal and axillary nodes	Paratracheal nodes and skin	Infection-related immune response	Not reported
Tigerightt et al., 1962³	56/F	Submandibular and cervical nodes	Axillary node	Infection-related immune response	Not reported
Kwittken et al., 1966⁴	83/F	Scalp	Scalp	Not reported	15 months
Burkitt & Kyalwazi, 1967⁵	9/M	Jaw	Jaw	Not reported	Not reported
Burkitt & Kyalwazi, 1967⁵	6/M	Mandible and maxilla	Mandible and maxilla	Not reported	14 months
Burkitt & Kyalwazi, 1967⁵	36/F	Breast and shoulder	Breast and shoulder	Not reported	Not reported
Burkitt & Kyalwazi, 1967⁵	4/F	Maxilla and orbit	Maxilla and orbit	Infection-related immune response	2 years
Burkitt, 1967⁶	Not reported	Blood	Blood, bone marrow	Immunological response	Not reported
David & Burkitt, 1968⁷	9/M	Maxilla, orbit, intracranial	Maxilla and orbit	Immunological response	2 months
David & Burkitt, 1968⁷	11/M	Maxilla	Maxilla	Immunological response	7 years
David & Burkitt, 1968⁷	6/F	Maxilla and abdomen	Not reported	Not reported	3 months
David & Burkitt, 1968⁷	7/F	Maxilla and abdomen	Not reported	Not reported	3 months
David & Burkitt, 1968⁷	15/M	Maxilla and orbit	Maxilla and orbit	Immunological response	3 years
David & Burkitt, 1968⁷	9/M	Maxilla, orbit, intracranial	Maxilla and orbit	Immunological response	10 months
David & Burkitt, 1968⁷	9/M	Maxilla	Maxilla	Immunological response	Not reported
David & Burkitt, 1968⁷	6/M	Maxilla and abdomen	Maxilla and abdomen	Immunological response	2 years
Kiely & Harrison, 1970⁸	16/M	Inguinal node	Inguinal and mediastinal nodes	Immunologic factors	5 years
Jamra et al., 1970⁹	12/F	Face, iliac fossa, ovary	Face and ovaries	Not reported	3 months
Bluming & Ziegler, 1971¹⁰	8/M	Orbit	Orbit	Infection-related immune response	4 months
Ziegler, 1976¹¹	Not reported	Blood	Blood	Antitumor immunity	Not reported
Gattiker et al., 1980¹²	Not reported	Not reported	Not reported	Not reported	several years
Krikorian et al., 1980¹³	42/M	Lymph nodes	Lymph nodes	Not reported	5 years
Krikorian et al., 1980¹³	43/F	Nodes	Peripheral and thoracic nodes	Not reported	32 months
Krikorian et al., 1980¹³	68/F	Nodes	Peripheral and abdominal nodes	Not reported	2 years
Krikorian et al., 1980¹³	42/M	Nodes	Peripheral and abdominal nodes	Not reported	5 years
Horning et al., 1984¹⁴	Not reported	Not reported	Lymph nodes	Viral infection, interferon effect	5–10 years
McClain et al., 1985¹⁵	12/F	Gastrointestinal tract, reproductive organs, CNS	Bone marrow	Infection-related immune response	11 months
Weaver et al., 1985¹⁶	69/F	Mediastinum	Mediastinum	Hormonal factors	27 days
Grem et al., 1986¹⁷	54/F	Tongue base	Cervical node	Infection-related immune response	4 years
Strauchen et al., 1987¹⁸	84/M	GI (stomach, antrum)	Stomach	Immunomodulatory effect	10 months
Strauchen et al., 1987¹⁸	73/M	GI (stomach, antrum)	Gastric antrum	Immunomodulatory effect	16 months
Poppema et al., 1988¹⁹	12/M	Tonsil and cervical node	Tonsil and cervical node	Host cytotoxic response	3 years
Shigematsu et al., 1989²⁰	40/F	Stomach (pyloric antrum)	Stomach	Not reported	69 months
Shigematsu et al., 1989²⁰	73/M	Stomach (posterior antrum)	Stomach	Not reported	44 months
Wolf, 1989²¹	56/F	Axilla and groin nodes	Epitrochlear and inguinal nodes	Infection-related immune response	>20 years
Drobyski et al., 1989²²	Not reported	Not reported	Not reported	Immune response, infection	Not reported
Aelbrecht & Geerights, 1990²³	75/F	Skin	Cutaneous lesions	Not reported	10 months
Mayou et al., 1991²⁴	43/F	Skin	Cutaneous nodules	Not reported	6 months
Daniels et al., 1992²⁵	43/M	Pharynx	Cervical nodes	Infection-related immune response	Infection-related immune response
Karnad et al., 1992²⁶	30/M	Skin and chest wall	Forehead and chest wall tumors	Immune response, interferon activity	Not reported
Grigg et al., 1992²⁷	67/M	Lymph nodes	Bone marrow and lymph nodes	Viral infection, immune response	16 months
Motley et al., 1992²⁸	27/F	Skin	Skin	Infection-related immune response	Not reported
Ranheim et al., 2000²⁹	35/M	Oral cavity, lung, bowel, spleen	Oral cavity, lung, bowel, spleen	Not reported	9 years
Takezako et al., 2000³⁰	79/F	Lymph nodes	Lymph nodes (inguinal, para-aortic)	Infection-induced immune response	18 months
Takenaka et al., 2000³¹	76/M	Rectum	Rectum	Not reported	19 months
Phanish et al., 2002³²	52/F	Spleen	Spleen	Not reported	14 months
Baird et al., 2002³³	69/F	Cervical lymph nodes	Cervical lymph nodes	Methotrexate withdrawal	14 months
Ohgi et al., 2002³⁴	61/F	Lumbar spine	Lumbar spine	Not reported	8 months
Mangel et al., 2003³⁵	47/M	Mediastinum (lymph nodes)	Mediastinum, and axillary lymph nodes	Not reported	15 months
Koga et al., 2003³⁶	78/F	Gingiva (left maxillary)	Gingiva (left maxillary)	Immune response	36 months
Ogata et al., 2004³⁷	70/M	Stomach	Stomach	Withdrawal of cyclosporine treatment	10 months
Heibel et al., 2004³⁸	70/M	Oral cavity (mandible)	Oral cavity (mandible)	Biopsy-induced apoptosis	20 months
Iihara et al., 2004³⁹	46/F	Breast (right)	Breast (right)	Biopsy-induced immune response	7 years
Chang et al., 2004⁴⁰	40/F	Conjunctiva	Conjunctiva and orbit	Biopsy-induced immune activation	5 weeks
Kumar et al., 2004⁴¹	45/M	Left axillary lymph nodes	Left axillary, mediastinal, and para-aortic lymph nodes	Not reported	6 months
Kumar et al., 2004⁴¹	59/F	Left parotid lymph node	Inguinal lymph nodes	Not reported	5 years
Kumar et al., 2004⁴¹	75/M	Posterior cervical lymph nodes (left neck)	Cervical lymph nodes	Not reported	14 months
Ugurlu & Bartley, 2004⁴²	76/M	Orbital apex	Orbital apex, frontal lobe	Not reported	2 years
Thonhofer et al., 2005⁴³	64/F	Sinuses	Sinuses	Methotrexate withdrawal	6 months
Futagami et al., 2005⁴⁴	36/M	Subcutaneous tissue (left thigh)	Subcutaneous tissue (left thigh)	Biopsy-induced immune response	6 months
Parekh et al., 2005⁴⁵	47/M	Cecum	Cecum	Antiretroviral therapy for HIV	5.5 years
Kamiya et al., 2006⁴⁶	72/M	Skin (left forearm)	Skin (left forearm)	Not reported	1 year
Kamiya et al., 2006⁴⁶	32/F	Skin (right cheek)	Skin (right cheek)	Not reported	2 years
Sakuma et al., 2006⁴⁷	70/F	Intraoral mucosa	Hard palate	Post-biopsy immune activation	38 months
Svensson et al., 2006⁴⁸	48/F	Bone marrow	Abdominal lymph nodes, bone marrow	Methotrexate withdrawal	12 months
Matsuo et al., 2007⁴⁹	72/M	Bilateral conjunctiva	Bilateral conjunctiva	Not reported	24 months
Patel et al., 2007⁵⁰	35/F	Left axilla	Left axilla	Not reported	2 years
Shimada et al., 2007⁵¹	54/F	Lungs	Lungs, liver, spleen	Methotrexate withdrawal	3 months
Armstrong et al., 2007⁵²	35/M	Oral cavity	Oral cavity	HAART-induced immune restoration	1 month
Abe et al., 2007⁵³	89/M	Inguinal lymph node	Inguinal and cervical lymph nodes	Immune modulation	31 months
Rujirojindakul et al., 2007⁵⁴	26/M	Submandibular gland	Lymph nodes	Immune response	6 months
Mohsin et al., 2007⁵⁵	48/M	Skin (anterior chest wall and back)	Skin (anterior chest wall and back)	Not reported	24 months
Daly et al., 2008⁵⁶	56/M	Oral cavity	Oral cavity	Biopsy-induced immune activation	4 years
McCabe et al., 2008⁵⁷	2/M	Right mastoid	Right mastoid	Not reported	24 months
Isobe et al., 2009⁵⁸	65/F	Skin (eyelid)	Submandibular lymph node	EBV-related immune activation	5 years
Chiu et al., 2009⁵⁹	64/M	Skin (right leg)	Skin (right leg)	Reduction of immunosuppression	9 months
Engel & Lee, 2009⁶⁰	Elderly/M	Cervical lymph nodes	Cervical, axillary, and tonsillar regions	Trauma-related immune activation	4 weeks
Makino et al., 2010⁶¹	38/M	Ileum mucosa	Ileum mucosa	Not reported	24 months
Rampisela & Donner, 2010⁶²	14/M	Lymph nodes	Lymph nodes	Not reported	4 years
Iwatani et al., 2011⁶³	69/F	Breast	Breast	Biopsy-induced immune response	Not reported
Norimura et al., 2011⁶⁴	59/F	Duodenum	Duodenum	Not reported	3-4 months
Norimura et al., 2011⁶⁴	76/F	Duodenum	Duodenum	Not reported	Not reported
Norimura et al., 2011⁶⁴	76/M	Duodenum	Duodenum	Not reported	Not reported
Norimura et al., 2011⁶⁴	72/M	Duodenum	Duodenum	Not reported	7 months
Norimura et al., 2011⁶⁴	67/F	Duodenum	Duodenum	Not reported	7 months
Norimura et al., 2011⁶⁴	72/F	Duodenum	Duodenum	Not reported	Not reported
Gencoglan et al., 2011⁶⁵	48/F	Skin (left forearm)	Skin (left forearm)	Biopsy-induced apoptosis	10 months
Cassaday et al., 2011⁶⁶	54/F	Intra-abdominal lymph nodes	Liver, spleen, and intra-abdominal lymph nodes	Withdrawal of adalimumab	3 months
Kameda et al., 2012⁶⁷	12/F	Cervical lymph nodes	Cervical lymph nodes, skin	Not reported	4 weeks
Kase et al., 2012⁶⁸	80/M	Eye	Intraocular tissues	Immune response, CD8 T cells	8 months
Buckner et al., 2012⁶⁹	67/F	Maxillary sinus	Maxillary sinus	Infection-induced immunity	1 year
Mohsen et al., 2012⁷⁰	86/F	Lymph nodes	Lymph nodes	Immune response	8 months
Biswas & Tan, 2012⁷¹	8/F	Skin	Left areola	Apoptosis	6 years
Zhang et al., 2013⁷²	24/F	Central nervous system and lungs	Brain and lung lesions	Improved immunity	1 year
Udupa et al., 2013⁷³	10/F	Lymph nodes	Lymph nodes, bone marrow, liver	Immune response	14 months
Mizuno et al., 2013⁷⁴	94/F	Lymph nodes	Lymph nodes	Immune recovery	10 months
Humeniuk et al., 2014⁷⁵	63/M	Lymph nodes	Lymph nodes	Not reported	12 months
Sekiguchi et al., 2014⁷⁶	68/F	Left breast	Left breast	Not reported	14 months
Rojas-Hernandez et al., 2014⁷⁷	57/M	Stomach	Gastric	Not reported	2 years
Kang et al., 2015⁷⁸	57/F	Lung	Lung	Apoptosis of lymphocytes	3 months
Kaibuchi et al., 2015⁷⁹	87/M	Gingiva	Gingiva	Biopsy-induced immune stimulation	2.5 years
Birendra et al., 2015⁸⁰	55/M	Kidney	Kidney	Immune reconstitution	10 months
Bekoz et al., 2015⁸¹	38/M	Lymph nodes	Axillary lymph nodes	Biopsy-induced trauma	Not reported
Igawa et al., 2015⁸²	80/M	Oral cavity	Gingiva	Immune response	5 months
Takahashi et al., 2015⁸³	61/F	Blood	Bone marrow	Apoptosis	6 years
Kato et al., 2015⁸⁴	60/F	Lymph nodes	Supraorbital region	Immune response	36 months
Ureshino & Miyahara, 2016⁸⁵	58/F	Blood	Blood and skin	Immune response	58 months
Ayala et al., 2016⁸⁶	62/M	Skin	Right cheek	Not reported	12 months
Ogihara et al., 2016⁸⁷	66/M	Urinary bladder	Urinary bladder	Recovery from immunosuppression	Not reported
Sasaki et al., 2016⁸⁸	83/F	Thyroid	Thyroid	Radiation exposure	9 years
Sasaki et al., 2016⁸⁸	51/F	Thyroid	Thyroid	Radiation exposure	8 years
Sasaki et al., 2016⁸⁸	60/M	Ileocecal region	Ileocecal region	Radiation exposure	Not reported
Sasaki et al., 2016⁸⁸	69/F	Thyroid	Thyroid	Radiation exposure	21 years
Fukushima et al., 2016⁸⁹	72/F	Lung	Lung	Biopsy-induced immune activation	40 months
Potts et al., 2017⁹⁰	59/M	Lymph nodes	Para-aortic lymph nodes	Biopsy-induced immune response	12 months
Hees et al., 2017⁹¹	20/M	Skin	Left alar base	Not reported	4 months
Cornish et al., 2017⁹²	66/M	Lymph nodes	Lymph nodes and spleen	Not reported	52 months
Chan et al., 2017⁹³	74/M	CNS	CNS	Immune response	2 years
Jimura et al., 2017⁹⁴	72/F	Skin	Left arm	Immune response	21 months
Miyagawa et al., 2017⁹⁴	46/M	Skin	Lip	Biopsy-induced immune activation	14 months
Fleming et al., 2018⁹⁵	51/F	Breast	Breast	Not reported	Not reported
Fleming et al., 2018⁹⁵	24/F	Breast	Breast	Not reported	Not reported
Ye et al., 2018⁹⁶	48/M	Right inguinal lymph node	Lymph nodes	Immune response	5 years
Ye et al., 2018⁹⁶	63/M	Right axillary lymph node	Lymph nodes	Immune response	3 years
Ye et al., 2018⁹⁶	68/M	Inguinal and cervical lymph nodes	Lymph nodes	Immune response	5 years
Ye et al., 2018⁹⁶	44/F	Inguinal and pelvic lymph nodes	Lymph nodes, Bone marrow	Immune response	1.5 years
Froehlich et al., 2018⁹⁷	44/F	Skin	Skin	Drug withdrawal immune restoration	4 weeks
Graham et al., 2018⁹⁸	79/M	Skin	Left leg	Immune response	12 months
Toberer et al., 2018⁹⁹	66/M	Skin	Left lower leg	Immune response	Not reported
Aiko et al., 2018¹⁰⁰	79/M	Lung	Lung	MTX withdrawal immune recovery	1 month
Swoboda et al., 2018¹⁰¹	66/M	Skin	Skin	Not reported	Few months
Pasvolsky et al., 2019¹⁰²	32/F	Lymph nodes	Lymph nodes	Not reported	2 years
Snijder et al., 2019¹⁰³	88/F	Lymph nodes	Lymph nodes	Biopsy-induced immune response	3 months
Tanaka et al., 2019¹⁰⁴	35/M	Small intestine	Small intestine, Lymph nodes	PD-L1/PD-1–mediated apoptosis	3 months
Yordanova et al., 2019¹⁰⁵	69/M	Bone marrow	Bone marrow, Spleen	Not reported	6 weeks
Hosoda et al., 2019¹⁰⁶	70/M	Bronchi	Bronchi	Not reported	Not reported
Morigi et al., 2019¹⁰⁷	47/M	Lymph nodes	Lymph nodes, Bone marrow, Spleen, Stomach	Immune response	3 months
Nakamoto et al., 2020¹⁰⁸	74/M	Liver	Liver, Spleen, Bone	Immune-mediated response	1.5 months
Tang et al., 2020¹⁰⁹	78/M	Skin	Skin	Not reported	8 months
Fleming et al., 2020¹¹⁰	24/F	Breast	Breast	Not reported	Not reported
Fleming et al., 2020¹¹⁰	51/F	Breast	Breast	Not reported	2 months
Stanoszek et al., 2021¹¹¹	35/M	Retroperitoneum	Retroperitoneum	Biopsy-induced immune response	6 months
Furukawa et al., 2021¹¹²	76/F	Vagina	Vagina, Lung	Not reported	1 year
Gambichler et al., 2021¹¹³	57/M	Lymph nodes	Lymph nodes	Vaccine-induced immune activation	1 month
Desana et al., 2021¹¹⁴	54/F	Cervix	Cervix	Biopsy-induced immune response	Not reported
Peeters et al., 2021¹¹⁵	59/M	Cheek	Cheek	T-cell–mediated immunity	5.5 months
Gong et al., 2021¹¹⁶	65/F	Vitreous	Vitreous	Not reported	1 week
Sherkat et al., 2022¹¹⁷	11/F	Lymph nodes	Lymph nodes, Spleen	Infection-related immune activation	Several months
Aoki et al., 2022¹¹⁸	84/M	Gingiva	Gingiva	Drug withdrawal effect	Not reported
Lee et al., 2022¹¹⁹	61/M	Sinus	Sinus	Biopsy-induced immune response	Not reported
Ogawa et al., 2022¹²⁰	63/F	Breast	Breast, lung, retroperitoneum	Methotrexate withdrawal	6 months
Kongwattananon et al., 2022¹²¹	80/M	Eye	Eye	Not reported	1 year
Gan et al., 2023¹²²	71/F	Eye	Eye	Biopsy-induced immune response	6 months
Hayashino et al., 2023¹²³	55/F	Pleura, Pericardium	Pleura, Pericardium	Not reported	Not reported
Li et al., 2023¹²⁴	62/M	Skin	Skin	Biopsy-induced immune response	3 months
Aizawa et al., 2023¹²⁵	15/M	Maxillary bone	Maxillary bone	Not reported	8 months
Abla et al., 2023¹²⁶	3/M	Lymph nodes	Lymph nodes	Not reported	3 weeks
Khaw et al., 2024¹²⁷	32/M	Colon	Brain, Colon	Immune reconstitution	1 year
Winkler et al., 2024¹²⁸	53/F	Skin	Skin	Reactive T-cell infiltration	9 years
Tomai et al., 2024¹²⁹	27/F	Mediastinum	Mediastinum, Lymph nodes	Feto-maternal microchimerism	6 months
Goto et al., 2024¹³⁰	75/F	Mandible	Mandible, Lungs	MTX withdrawal immune recovery	6 months
Teoh et al., 2025¹³¹	35/M	Skin	Skin	Immune reconstitution	3 months
Li et al., 2025¹³²	72/M	Lung	Lung	Biopsy-induced immune response	5 months
Moreno et al., 1991¹³³	79 -year-old male, has severe androgenic alopecia	forehead and anterior scalp	two months later after cholorquine treatment, the lesions began to resolve spotaneousaneoulsy the regression was completed within 2 months without any clinical residue The biopsies from resolving lesions exhibited involutive changes, with follicular hyalinization and infiltration by plasma cells, the follicular centers were less prominent or even inconspicuous	no major mechanism proposed	two months later after cholorquine treatment, the lesions began to resolve spotaneousaneoulsy the regression was completed within 2 months without any clinical residue The biopsies from resolving lesions exhibited involutive changes, with follicular hyalinization and infiltration by plasma cells, the follicular centers were less prominent or even inconspicuous
Moreno et al., 1991¹³³	83 -year-old male past history of hypertrophic cardiopathy and obliterant atherosclerosis with chronic ischemia of the legs	face, neck, trunk	some of the lesions became less prominent and began to fade during the immediate follow-up after six months, only a few lesions remained and they were receding The biopsies from resolving lesions exhibited involutive changes, with follicular hyalinization and infiltration by plasma cells, the follicular centers were less prominent or even inconspicuous	no major mechanism proposed	some of the lesions became less prominent and began to fade during the immediate follow-up after six months, only a few lesions remained and they were receding The biopsies from resolving lesions exhibited involutive changes, with follicular hyalinization and infiltration by plasma cells, the follicular centers were less prominent or even inconspicuous
Weintraub, 1969¹³⁴	68 -year-old male caucasion	axillary and inguinal regions	4 weeks following the treatment, the night sweats disappeared, the spleen decreased in size to 4cm below the left costal margin and the liver to 2cm below the right costal margin. This was associated with a fall in the WBC to 8k/mm^3, hemoglobin to 9.5gm/100cc, and platelet count to 74k/mm^3 once admitted to the hospital for the serum hepatitis, during the following 7 days the bilirubin and transaminase levels began to fall. Hepatic tenderness disappeared and the liver decreased in size as the patient's appetite returned to normal. He was discharged to convalesce at home. within one months, liver function results were normal. Hemoglobin concentration continued to rise and in 3 weeks a plateau in the range of 14gm/100cc. 12 months after the episode of hepatitis, in May 1967, the patient was in excellent condition, returning to full activity, gained 9.1 kg and denied any fatigue or night sweats. A few small 0.5cm axillary and inguinal nodes were palpable, the liver was palpable 1.5cm below the right costal margin. Hemoglobin was 14.5gm/100cc, WBC 18k/mm^3 with 75% neutrophilic granulocytes. Bone marrow revealed normal granulocytic and erythroopoietic maturation. Megakaryocytes were present in adequate numbers and there was no lymphocytic infiltration "complete remission"	suggestion of the production of interferon by virus	4 weeks following the treatment, the night sweats disappeared, the spleen decreased in size to 4cm below the left costal margin and the liver to 2cm below the right costal margin. This was associated with a fall in the WBC to 8k/mm^3, hemoglobin to 9.5gm/100cc, and platelet count to 74k/mm^3 once admitted to the hospital for the serum hepatitis, during the following 7 days the bilirubin and transaminase levels began to fall. Hepatic tenderness disappeared and the liver decreased in size as the patient's appetite returned to normal. He was discharged to convalesce at home. within one months, liver function results were normal. Hemoglobin concentration continued to rise and in 3 weeks a plateau in the range of 14gm/100cc. 12 months after the episode of hepatitis, in May 1967, the patient was in excellent condition, returning to full activity, gained 9.1 kg and denied any fatigue or night sweats. A few small 0.5cm axillary and inguinal nodes were palpable, the liver was palpable 1.5cm below the right costal margin. Hemoglobin was 14.5gm/100cc, WBC 18k/mm^3 with 75% neutrophilic granulocytes. Bone marrow revealed normal granulocytic and erythroopoietic maturation. Megakaryocytes were present in adequate numbers and there was no lymphocytic infiltration "complete remission"
Buchi et al., 1983¹³⁵	76-year-old woman	lymph nodes	In the following years, we remarked a gradual and more and more striking regression of the lymph- adenopathies. In April 1980, the lymphadenopathies disappeared. Bone marrow aspiration disclosed 8% of lymphocytes. Bone marrow biopsy showed that the structure of the bone was normal. Diffuse infiltra tion with lymphoid cells or disperse accumulations of small lymphocytes were not found. A computed tomographic (CT) of the abdomen showed neither an enlargement of the pelvic or lumboaortic lymphnodes nor an involvement of the liver or spleen	immune reaction	In the following years, we remarked a gradual and more and more striking regression of the lymph- adenopathies. In April 1980, the lymphadenopathies disappeared. Bone marrow aspiration disclosed 8% of lymphocytes. Bone marrow biopsy showed that the structure of the bone was normal. Diffuse infiltra tion with lymphoid cells or disperse accumulations of small lymphocytes were not found. A computed tomographic (CT) of the abdomen showed neither an enlargement of the pelvic or lumboaortic lymphnodes nor an involvement of the liver or spleen
Buchi et al., 1983¹³⁵	76-year-old woman		Gradual and more and more striking regression of the lymphadenopathies, white cell count was 4.2 x 109/l with 60% lymphocytes, bone marrow aspirate disclosed 21% of lymphocytes, lymphadenopathies were disappeared, bone marrow biopsy showed that the structure of the bone was normal	The cause of the remission and its possible connection with the imbalanced distribution of the T lymphocytic subsets is discussed	Gradual and more and more striking regression of the lymphadenopathies, white cell count was 4.2 x 109/l with 60% lymphocytes, bone marrow aspirate disclosed 21% of lymphocytes, lymphadenopathies were disappeared, bone marrow biopsy showed that the structure of the bone was normal
Kwittkin & Goldberg et al., 1966¹³⁶	83 -year-old female puertorican developed congestive heart failure secondary to hypertension and ARTeriosclerotic heart disease in about 1960. Chest x-rays at that time revealed slight left ventricular enlargement and mild basilar pulmonary fibrosis her condition was well controlled with digitalis, oral diuretic, and antihypertensive medication in 1962, she had slightly elevated hemoglobin and hematocrit values consistent with a mild secondary polycythemia pulmonary function tests demonstrated abnormalities which were compatible with congestive heart failure and pulmonary fibrosis.	scalp	during the 8 months period from clinic visits, most of the scalp lesion had spontaneously involuted only two small, contiguous, erithematous, firm nodules measuring 0.8 and 0.4cm in diameter remained in the region In october 1964, the smaller scalp nodule regressed and the larger one had softened These disappeared by December, leaving a poorly defined area of atrophic skin, 4.0x6.0cm with zones of hypopigmentation and hyperpigmentation the patient felt well	there may be some relationship to histologic type considered local trauma but were doubted by the authors no major mechanism proposed	during the 8 months period from clinic visits, most of the scalp lesion had spontaneously involuted only two small, contiguous, erithematous, firm nodules measuring 0.8 and 0.4cm in diameter remained in the region In october 1964, the smaller scalp nodule regressed and the larger one had softened These disappeared by December, leaving a poorly defined area of atrophic skin, 4.0x6.0cm with zones of hypopigmentation and hyperpigmentation the patient felt well
Stevanovic & Majcan et al., 1961¹³⁷	26 -year-old female	cutaneous (face) genital area	Healing of the curetted tumor was observed; lymph glands also became smaller The curettage of the forehead tumor had the same clinical and pathohistological result the genital tumor was curetted and soon recurred only on one site, while the other part formed a scar; a second curettage brought complete healing no new tumor was seen and she was discharged 2 months after admission the right-reauricular infiltrate gradually completely thawed and the lymph glands shrank after the deep x-ray the patient comes for 2 monthly regular exams, at the time of last exam - 1 year after the last tumor appearance, no new tumor had appeared, all tests were normal	progressive fibrosis was also the probably cause of the small tumor an inflammatory process often precedes SR	Healing of the curetted tumor was observed; lymph glands also became smaller The curettage of the forehead tumor had the same clinical and pathohistological result the genital tumor was curetted and soon recurred only on one site, while the other part formed a scar; a second curettage brought complete healing no new tumor was seen and she was discharged 2 months after admission the right-reauricular infiltrate gradually completely thawed and the lymph glands shrank after the deep x-ray the patient comes for 2 monthly regular exams, at the time of last exam - 1 year after the last tumor appearance, no new tumor had appeared, all tests were normal
Stevanovic & Majcan et al., 1961¹³⁷	36 -year-old male	cutaneous (back)	when the new neck and face tumors appeared, the back tumors had completely regressed SR was evidence histologically by an increased growth of fibroblasts and greater amounts of collagen bundles among which lymphoid cells and histiocytes were seen	regression of neoplasms during radiation, antimitotic and hormonal therapy, is party ascribed to connective tissue alteration	when the new neck and face tumors appeared, the back tumors had completely regressed SR was evidence histologically by an increased growth of fibroblasts and greater amounts of collagen bundles among which lymphoid cells and histiocytes were seen
Gurcay, 1969¹³⁸	16 -year-old male	mediastinal mass and cervical lymph nodes	on the 4th day of hospitalization, a day after biopsies, the left cervical nodules had very much decreased in size and number, and an immediate chest xray was taken and showed that the mediastinal mass had also regressed. A repeat xray the same day verified that finding.	SR followed a biopsy, so it could have be the surgical exploration also mention of procaine having a role in the regression the role of the thymus gland on the lymphocytes and the lymphoid tissues, i.e. interplay between the thymic hormones and the substances containing procaine LN biopsies are regularly perfromed using local anestehtic, which procaine is the most universal	on the 4th day of hospitalization, a day after biopsies, the left cervical nodules had very much decreased in size and number, and an immediate chest xray was taken and showed that the mediastinal mass had also regressed. A repeat xray the same day verified that finding.
Monthstanaro & Patton et al., 1976¹³⁹	61 -year-old female caucasian	spleen	postop recovery was uneventful and the patient was discharged on May 10, 1964 with no further surgery or therapy the patient was last seen in December 1974 (~11 years later) for a biopsy of a right breast mass (fibrocystic diseases), she currently has no clinical evidence of malignancy	removal of the spleen	postop recovery was uneventful and the patient was discharged on May 10, 1964 with no further surgery or therapy the patient was last seen in December 1974 (~11 years later) for a biopsy of a right breast mass (fibrocystic diseases), she currently has no clinical evidence of malignancy
Williams, 1980¹⁴⁰	46 -year-old male	left axilla, skin	the skin nodules resolved spontaneously within one months at about the same time the patient's hair started to regrow there has been no further evidence of recurrent hodgkin's disease two and half years after treatment	no major mechanism proposed	the skin nodules resolved spontaneously within one months at about the same time the patient's hair started to regrow there has been no further evidence of recurrent hodgkin's disease two and half years after treatment
Green et al., 1984¹⁴¹	48 -year-old female	bilateral cervical and axillary, mediastinal nodes	after local radiotherapy, she remained well until 1975 chemo in 1979 resulted in a good response and she remained in complete remission until February 1981	no major mechanism proposed	after local radiotherapy, she remained well until 1975 chemo in 1979 resulted in a good response and she remained in complete remission until February 1981
Green et al., 1984¹⁴¹	42 -year-old male	left supraclavicular node	after the radiation, he remained well until March 1981 his relapse is in complete remission following chemotherapy in June 1982 with chlorambucil, vinblastine, procabazine and prenisolone	no major mechanism proposed	after the radiation, he remained well until March 1981 his relapse is in complete remission following chemotherapy in June 1982 with chlorambucil, vinblastine, procabazine and prenisolone
Alcantara-Gozalez et al., 2014¹⁴²	82 -year-old female history of hypertension, chronic atrial fibrillation, and 2 cerebrovascular accidnets, the second of which occurred 6 years before she underwent surgery for varicose veins in both legs and placement of a prosthesis in the right hip she regularly takes omeprazole, digoxin, torsemide, and acetylsalicylic acid	skin on right leg	4 weeks later after first visit, the skin lesions had almost completely disappeared, with only what seemed to be a residual erythematous-brownish macules remaining the biopsy revealed a diffuse infiltrate composed of mature T cells (CD3+) with scant foci of atypical cells expressing CD20 and bcl-2 -- findings consistent with almost complete regression	the infiltrate could have contributed to the regression of the malignancy	4 weeks later after first visit, the skin lesions had almost completely disappeared, with only what seemed to be a residual erythematous-brownish macules remaining the biopsy revealed a diffuse infiltrate composed of mature T cells (CD3+) with scant foci of atypical cells expressing CD20 and bcl-2 -- findings consistent with almost complete regression
Gonzalez et al., 2015¹⁴³	44 -year-old male no past history of interest	left nasal ala	10 days after the biopsy, the lesion was seen to regress and it had completely disappeared after 3 months after a year, the patient remained asymptomatic and no new lesions had appeared	no major mechanism reported	10 days after the biopsy, the lesion was seen to regress and it had completely disappeared after 3 months after a year, the patient remained asymptomatic and no new lesions had appeared
Marrero-Aleman et al., 2017¹⁴⁴	83 -year-old female background of arterial hypertension	back of right leg	3 months later, before started radiotherapy, the lesions regress spontaneously, leaving 2 brown macules with irregular, diffuse outlines, not infiltrated Complete regression was determinedly the results of the second biopsy patient remains asymptomatic after 1 year follow-up there was a T lymphocytary infiltARTe with clear predominance of CD8	an immune response against tumor cells through traumatic or infectious mechanisms	3 months later, before started radiotherapy, the lesions regress spontaneously, leaving 2 brown macules with irregular, diffuse outlines, not infiltrated Complete regression was determinedly the results of the second biopsy patient remains asymptomatic after 1 year follow-up there was a T lymphocytary infiltARTe with clear predominance of CD8
Monthszen et al., 2013¹⁴⁵	85 -year-old male was diagnosed with prostatic hypertrophy in 2003	prostate	precontrast CT demonstrated a diminution of the size of the lymphoma after the prostate biopsy, the two enlarged lymph nodes in the pelvis disappeared and both the left hydronephrosis and the hydroureter improved there has been no local recurrence or distant metastasis in the 31 month since the biopsy	probably attributable to immunological response by the host that arises as a result of the injury due to an infection with bacteria or viruses or the injury caused by the biopsy of the prostate the etiology of SR in this case is likely a result from biopsy	precontrast CT demonstrated a diminution of the size of the lymphoma after the prostate biopsy, the two enlarged lymph nodes in the pelvis disappeared and both the left hydronephrosis and the hydroureter improved there has been no local recurrence or distant metastasis in the 31 month since the biopsy
Adiquzel et al., 2009¹⁴⁶	89 -year-old male july 2004 had diabetes mellitus, hypertension and coronary arterial disease	Body cavities	during follow-up period, symptoms resolved and right pleural effusion resolved. A year later was re-admitted with left side plerual effusion 40 months after initial diagnonsis was without symptoms	None reported	during follow-up period, symptoms resolved and right pleural effusion resolved. A year later was re-admitted with left side plerual effusion 40 months after initial diagnonsis was without symptoms
Blokx et al., 2012¹⁴⁷	65 -year-old female May 2000 Renal transplantation in 1979, likely due to chronic pyelonephritis, never had a period of rejection osteoporosis of lumbar spine	skin ulcer thalamus	a few weeks later after biopsy, witho further clinical intervention, the ulcer showed complete clinical regression CT scans of thorax, abdomen, and X-thorax showed neither enlarged lymph nodes nor abnormalities in organs including the transplant kidney Bone marrow biopsy were normal stay disease free for 18 months after initial diagnosis then developed a progressive hemiparesis and died of acute myocardial infarction	antiviral treatment and reduction/discontinuation of immunosuppression cutaneous B-cell PTLD has been treated with surgery or radiotherapy	a few weeks later after biopsy, witho further clinical intervention, the ulcer showed complete clinical regression CT scans of thorax, abdomen, and X-thorax showed neither enlarged lymph nodes nor abnormalities in organs including the transplant kidney Bone marrow biopsy were normal stay disease free for 18 months after initial diagnosis then developed a progressive hemiparesis and died of acute myocardial infarction
Lelievre, 2005¹⁴⁸	52 -year-old male, caucasian 1986 was enrolled in a cyclosporine therapy for psoriasis vulgaris. Methotrexate was given before for 6 months but was discontinued because of hepatic side effects. The cyclosporine resulted in a complete disappearance of dermatologic lesions	splenomegaly, axillary, inguinal, and cervical lymph nodes	after the transient worsening, the patients status gradually improved without additional treatment. One months later, all biologic abnormalities had disappeared. Small cervical and axillary lymph nodes were still detectable but splenomegaly had regressed. 30 months later, he had no evidence of relate and psoriasis was controlled by topical treatment	discontinuation of the cyclosporine therapy	after the transient worsening, the patients status gradually improved without additional treatment. One months later, all biologic abnormalities had disappeared. Small cervical and axillary lymph nodes were still detectable but splenomegaly had regressed. 30 months later, he had no evidence of relate and psoriasis was controlled by topical treatment
Parekh & Koduri et al., 2003¹⁴⁹	46 -year-old male HIV-seropositive for 14 years May 2001	left axilla and left chest spleen, liver lymph nodes	4 weeks after the parathyroidectomy, he was well with no change in body weight the previous left pectoral mass was no longer palpable the mass in the left axilla had virtually pompletely resolved leaving only a single, 2cm firm ovoid LN along the medial wall serum calcium was normal repeat CT with contrast showed resolution of the left subpectoral mass of nodes and the left axillary LN mas now measured 3cm. Findings in the abdomen showed no change	no major mechanism proposed immunologic defences	4 weeks after the parathyroidectomy, he was well with no change in body weight the previous left pectoral mass was no longer palpable the mass in the left axilla had virtually pompletely resolved leaving only a single, 2cm firm ovoid LN along the medial wall serum calcium was normal repeat CT with contrast showed resolution of the left subpectoral mass of nodes and the left axillary LN mas now measured 3cm. Findings in the abdomen showed no change
Tamas et al., 2011¹⁵⁰	66 -year-old female 2003 history of hysterectomy due to leiom-year-old malea as well as total adnexectomy also endometrioid neoplasia in the ovaries no medicine on a regular basis	tongue (left vallecula and root of the tongue)	"all the ARTicle mentions was the ""we became passive witnesses of the SR of an activated B-cell type DLBCL"" occurred along 7 years, untreated"	immunological mechanisms, endocrine mechanisms, elimination of the carcinogenic factor, apoptosis, epigenetical, and psychological factors no major mechanism proposed for this case	"all the ARTicle mentions was the ""we became passive witnesses of the SR of an activated B-cell type DLBCL"" occurred along 7 years, untreated"
Nishimura, 2021¹⁵¹	23-year-old Japanese female	bilateral areolae	By 6-months of follow-up, her skin lesions and itching both disappeared completely, with neither abrupt pigmentation nor did it provoke scar formation	self-limited disease and underlying pathology of inflammatory variant of an epidermal nevus with spontaneous regression vs Skin biopsy triggered regression.	By 6-months of follow-up, her skin lesions and itching both disappeared completely, with neither abrupt pigmentation nor did it provoke scar formation
Takatsu, 2021¹⁵²	69-year-old right-handed man	brain	On repeat MRI 7 days later, FLAIR hyperintense lesions that had been apparent in the right deep white matter had spontaneously disappeared and white matter hyperintensities were seen on FLAIR surrounding bilateral post- rior horns of the lateral ventricles, appearing more prominently on the left	serial changes in MRI represented the regression and progression of inflamma- tion	On repeat MRI 7 days later, FLAIR hyperintense lesions that had been apparent in the right deep white matter had spontaneously disappeared and white matter hyperintensities were seen on FLAIR surrounding bilateral post- rior horns of the lateral ventricles, appearing more prominently on the left
Han & Sokal et al., 1971¹⁵³	H. B., a 69-year-old woman		excellent partial remission, characterized by disappearance of lymphadenopathy and hepatosplenomegaly, rise in hemoglobin and significant fall in lymphocyte count, total white blood cell count fell to normal levels, lymphadenopathy and hepatosplenomegaly had regressed markedly, Hemoglobin was 12.8 gm/100 ml, platelet count 280,000/mm3, white blood cell count 9,943/mm3 with 67% lymphocytes, normal lymphocyte count was reached in September 1966		excellent partial remission, characterized by disappearance of lymphadenopathy and hepatosplenomegaly, rise in hemoglobin and significant fall in lymphocyte count, total white blood cell count fell to normal levels, lymphadenopathy and hepatosplenomegaly had regressed markedly, Hemoglobin was 12.8 gm/100 ml, platelet count 280,000/mm3, white blood cell count 9,943/mm3 with 67% lymphocytes, normal lymphocyte count was reached in September 1966
Getzen, 1967¹⁵⁴	41-year-old menstruating woman		spontaneous remission, no evidence of recurrent bleeding, coagulation studies have now remained entirely normal		spontaneous remission, no evidence of recurrent bleeding, coagulation studies have now remained entirely normal
Houbouyan et al., 1984¹⁵⁵	A 2-year-old female		spontaneous and quick recovery		spontaneous and quick recovery
Ziliotto & Miotto et al., 1980¹⁵⁶	over 80-year-old female		spontaneous remission of the adenopathy, progressive normalization of the protein disorder, lymph node cellular depletion with the persistence only of the lymphocytes		spontaneous remission of the adenopathy, progressive normalization of the protein disorder, lymph node cellular depletion with the persistence only of the lymphocytes
Fiorillo et al., 1981¹⁵⁷	childhood		evolved toward a spontaneous remission		evolved toward a spontaneous remission
Matthews et al., 1988¹⁵⁸	A man		spontaneous remission that lasted 18 years, another remission was induced by prednisolone	development of a lymphoid stem cell clone with no TcR gene rearrangement, a sub-clone bearing the TcR gamma gene rearrangement proliferated in the lymph nodes and further heterogeneous rearrangement of the TcR beta genes occurred within this subclone	spontaneous remission that lasted 18 years, another remission was induced by prednisolone
Fatkenheuer et al., 2000¹⁵⁹
Lin et al., 2002¹⁶⁰
Machida et al., 2003¹⁶¹
Mitchell et al., 2012¹⁶²
Ohta, 2003¹⁶³
Rizzi et al., 2009¹⁶⁴
Kawabata et al., 2001¹⁶⁵
Penichet et al., 2001¹⁶⁶
Yao et al., 2012¹⁶⁷
Sun, 2022¹⁶⁸
Torisu, 2022¹⁶⁹
Ilan et al., 1990¹⁷⁰
Bittencourt et al., 1992¹⁷¹
Zygiert, 1971¹⁷²
Swerdlow¹⁷³
David¹⁷⁴
Jamra et al.¹⁷⁵
Bluming¹⁷⁶
Montanaro¹⁷⁷
Pentimone et al.¹⁷⁸
Adiguzel et al.¹⁷⁹
Tamás et al.¹⁸⁰
Biswas¹⁸¹
Monzen et al.¹⁸²
Alcántara-González et al.¹⁸³
Marrero-Alemán et al.¹⁸⁴
Cornish et al.¹⁸⁵

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