Thyroid cancer
Epidemiology:
Thyroid cancer is increasingly recognized as a significant public health concern, given its rising incidence rate globally, particularly among women 1. Spontaneous remission (SR) in thyroid cancer, particularly in its differentiated forms, is an exceptionally rare phenomenon, reported in roughly 1 in 60,000 to 100,000 cases of cancer overall 2. While specific data on SR within thyroid carcinomas is limited, cases have been documented primarily in rare lymphomas associated with the thyroid, highlighting the sporadic nature of such events. The rarity of SR makes its study complex, as many instances go unreported unless the remission is notably marked and enduring; hence, assessing the true prevalence within thyroid malignancies poses a challenge 3.
Clinical Characteristics:
To date, there have been nine reported cases of spontaneous regression involving thyroid malignancies. Several clinical patterns can be observed among these cases. The patients’ ages at the time of regression ranged from 13 to 83 years, with a clear predominance in females. All reported cases involved the thyroid gland as the primary site, with remission occurring either within the thyroid itself or in regional lymph nodes. Proposed mechanisms included hemorrhagic necrosis, biopsy-induced immune response, and low-dose radiation exposure, although several cases did not report a specific cause. See Table 1 below for further information.
Histological Characteristics:
Of the cases analyzed, the histological types primarily included thyroid carcinomas, with one case involving primary thyroid lymphoma. Other thyroid lesions or benign nodular conditions were excluded from this data collection to maintain focus on malignant spontaneous regression cases.
Proposed Contributing Mechanisms:
Among the reported cases, the proposed mechanisms of spontaneous regression varied notably. In three patients, regression was associated with prior exposure to low-dose radiation, suggesting a possible radiation-induced immune or apoptotic response. One case attributed tumor regression to hemorrhagic necrosis within the thyroid tissue, while another implicated biopsy-induced immune activation as a triggering event. The remaining cases did not report a specific cause of regression. Collectively, these observations suggest that physical injury, radiation exposure, and immune stimulation may each contribute to the spontaneous regression of thyroid malignancies.
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 of the primary thyroid lesion, while a few also showed resolution of metastatic involvement, particularly in regional lymph nodes. The duration of follow-up ranged from several months to over two decades, with some patients maintaining long-term remission for up to 21 years. Although follow-up data were not uniformly available, these reports suggest that spontaneous regression in thyroid malignancies can, in certain cases, result in durable disease control, distinguishing it from the more transient regressions observed in other cancer types.
Table 1: Thyroid Cancer SR Cases and Clinical Characteristics
Author–year | Age/sex | Primary site | Remission site | Proposed mechanisms | Follow-up |
|---|---|---|---|---|---|
24/F | Thyroid | Thyroid | Not reported | 21 months | |
13/F | Thyroid | Thyroid | Hemorrhagic necrosis | Not reported | |
69/F | Thyroid | Thyroid and lymph nodes | Low-dose radiation exposure | 21 years | |
83/F | Thyroid | Thyroid | Low-dose radiation exposure | 9 years | |
51/F | Thyroid | Thyroid | Low-dose radiation exposure | 8 years | |
58/F | Thyroid | Lymph node | Not reported | 9 years | |
63/F | Thyroid | Thyroid | Biopsy-induced immune response | 5 months | |
80-year old man with previous history of pneumonia, paroxysmal atrial fibrillation and hypertension; received surgery for early gastric therapy | transverse colon | 2 weeks after diagnosis, surgery was performed but no tumour was found in excised specimen, histopathology showed inflammatory cell infiltration and fibrosis from the submucosal to MP layers and surface covered by regenerative mucosa without glandular cavity, no cancer cells detected, immunohistological staining of excised specimen showed significant amount of CD3+CD4+ T cells and CD20+ B cells and a few CD8+ T cells observed; CS performed 5 months after surgery showed absense of tumours in colon and rectum and CA19-9 level decreased to normal range | adapatientive immunological response to the carcinoma that is mediated particularly by CD4+ T cells | 2 weeks after diagnosis, surgery was performed but no tumour was found in excised specimen, histopathology showed inflammatory cell infiltration and fibrosis from the submucosal to MP layers and surface covered by regenerative mucosa without glandular cavity, no cancer cells detected, immunohistological staining of excised specimen showed significant amount of CD3+CD4+ T cells and CD20+ B cells and a few CD8+ T cells observed; CS performed 5 months after surgery showed absense of tumours in colon and rectum and CA19-9 level decreased to normal range | |
45-year-old woman, had been diagnosed with Takayasu arteritis (TAK) at age 36 | Carotid artery | After 2 weeks, she spontaneously became afebrile and the cervical pain resolved, with a normalized CRP level. MRI after 3 months also showed no enhancement of the carotid vascular walls | LVV may resolve spontaneously in some patients with TAK or neoplasm | After 2 weeks, she spontaneously became afebrile and the cervical pain resolved, with a normalized CRP level. MRI after 3 months also showed no enhancement of the carotid vascular walls | |
64-year-old man | arteries | At the time of surgery, CRP and vascular uptake on PET had normalized | LVV may resolve spontaneously in some patients with TAK or neoplasm | At the time of surgery, CRP and vascular uptake on PET had normalized | |
six women and two men | regression or resolution was established by means of scintigraphy after a period varying from one to about four years. One of the cases with an initial warm nodule developed a hot nodule about two years after regression. In the two slightly hyperthyroid cases, the resolution of the nodule coincided with the disappearance of the symptoms. | evolution of AHTA towards regression or resolution | regression or resolution was established by means of scintigraphy after a period varying from one to about four years. One of the cases with an initial warm nodule developed a hot nodule about two years after regression. In the two slightly hyperthyroid cases, the resolution of the nodule coincided with the disappearance of the symptoms. | ||
23 1/2-year-old male | The mass was smaller the day after the FNAB and continued to shrink, until, by the 26th day, it no longer was felt. The 24-hour uptake of radioiodide was 26%, and the scan now disclosed a normal bilobed thyroid gland with no trace of the original nodule. | The mass was smaller the day after the FNAB and continued to shrink, until, by the 26th day, it no longer was felt. The 24-hour uptake of radioiodide was 26%, and the scan now disclosed a normal bilobed thyroid gland with no trace of the original nodule. | |||
A 31-year-old woman | Serum T4 was now within the normal range (82 nanomoles/l) as was the serum TSH (1.8 mU/l). Over the next 12 months and on no treatment, she remained symptom-free and biochemically euthyroid with the serum TSH levels repeatedly less than 1 mU/l. Tests for antithyroid microsomal antibodies became weakly positive (+), and there was a marked reduction in the size of the goitre | Serum T4 was now within the normal range (82 nanomoles/l) as was the serum TSH (1.8 mU/l). Over the next 12 months and on no treatment, she remained symptom-free and biochemically euthyroid with the serum TSH levels repeatedly less than 1 mU/l. Tests for antithyroid microsomal antibodies became weakly positive (+), and there was a marked reduction in the size of the goitre | |||
Thyroid function fluctuated spontaneously during the course of the disease | Thyroid function fluctuated spontaneously during the course of the disease | ||||
References:
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- Sasaki et al., 1984. Spontaneous Remission of Hypothyroidism in Hashimotos (Autoimmune) Thyroiditis. Israel Journal of Medical Sciences 20(7): July 1984; 625-629
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- Vaisman, F., Momesso, D., Bulzico, D. A., Pessoa, C. H., Dias, F., Corbo, R., . . . Tuttle, R. M. (2012). Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy. Clinical Endocrinology, 77(1), 132-138. doi:10.1111/j.1365-2265.2012.04342.x;
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