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Is Adenoid Cystic Carcinoma Curable

Prognosis Of Adenoid Cystic Carcinoma

External Auditory Canal Adenoid Cystic Carcinoma

It is not possible for a doctor to predict the exact course of a disease, as it will depend on each person’s individual circumstances. However, your doctor may give you a prognosis – the likely outcome of the disease – based on the test results, the rate of tumour growth, as well as your age, fitness and medical history.

The Epigenome As A Stemness Target

The inhibitor of the protein arginine methyltransferase 5 may also have a therapeutic effect in ACC. PRMTs are involved in various signal transduction cascades by catalyzing methylation of specific arginine residues. Overexpression of PRMT5 has been confirmed in many carcinomas and is thought to have a role in cancer progression by inhibiting tumor suppressor gene expression via methylation of transcription factors and chromatin associated proteins . In oropharyngeal cancers, high expression of PRMT5 in the nucleus indicates poor prognosis. Notably, and it has been shown that IL-6 promotes PRMT5 translocation into the nucleus . In breast cancer, PRMT5 was overexpressed in chemoresistant cell lines compared to non-resistant cell lines. Conversely, it was observed that knocking down PRMT5 enhances drug sensitivity. In addition, PRMT5 knockdown inhibits sphere formation and decreases the CSC fraction identified as CD44+CD22- . Therefore, it is likely that PRMT5 has an association with carcinogenesis and cancer stemness. Preclinical studies showing a relationship between salivary gland carcinoma and PRMT5 are inadequate, but clinical trials have shown some promise for ACC. Although it is an intermediate result of a Phase I trial, PR was confirmed in 3 out of 14 patients in the ACC patient group treated with GSK3326595, which is a PRMT5 inhibitors . In addition, another PRMT5 inhibitor is also undergoing phase I studies in patients with ACC .

P53 As A Stemness Target

Mutations in the TP53 gene are the most frequently found in human cancer. Indeed, p53 is known as the guardian of the genome playing a key role in the determination of cell fate. Under normal conditions, p53 is under tight molecular regulation. However, once the gene is mutated, it is released from the degradation mechanism of p53 and accumulates rapidly in the cell to promote various transcription factors involved in senescence and apoptosis. Mouse double minute 2 is a major negative regulator of p53 that promotes degradation of p53 upon direct binding . It is considered that malignant tumors survive because p53 itself does not have proper function due to an abnormality in itself or an abnormality in the binding to MDM2 .

There is some relationship between p53 and CSCs regarding stem cell self-renewal and differentiation . In studies with mammary stem cells, p53 deficiency increased self-renewal capacity, increased the stem cell pool, and promoted symmetric division of cells. p53 knockout mice were found to have a higher proportion of cells capable of generating mammospheres, supporting the concept that p53 plays an important role in the generation and maintenance of the cancer stem cell pool . In addition, p53 promotes differentiation by suppressing the expression of Nanog in mouse embryonic stem cells . Given these findings, it is concluded that p53 controls the balance between self-renewal and differentiation of stem cells.

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What We Offer You For Adenoid Cystic Carcinoma

  • Globally-recognized expertise in the diagnosis and treatment of adenoid cystic carcinomas.
  • Team-based treatment planning that brings together specialists from neuroradiology, radiation oncology, neuropathology, and more.
  • Advanced treatment options usually begin with scarless endoscopic surgery through the nostril and follow with radiation therapy,
  • Comprehensive support services like occupational or physical rehabilitation, nutritional and emotional support to help you with your specific symptoms and the challenges of this experience.
  • An active clinical research program dedicated to broadening options for the diagnosis and treatment of adenoid cystic carcimona.
  • Assistance from our International Medical Services team to plan your travel and accommodations.

Who Is At Risk Of Primary Cutaneous Adenoid Cystic Carcinoma

Adenoid Cystic Carcinoma

PCACC usually affects adults with fair complexion. It typically occurs between the ages of 50 and 70 years old. It occurs in men and women equally and more frequently with increasing age.

While immunosuppression increases the risk for some other cancers such as squamous cell carcinoma , this does not increase the risk of PCACC.

Due to the rarity of this cancer, other risk factors have not yet been identified.

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How Adenoid Cystic Carcinoma Is Treated

Treatment for adenoid cystic carcinoma , a rare type of cancer that affects glandular tissue, is determined by your medical care team based on several factors. Treatment typically includes surgical removal of the cancerous tissues along with some form of additional therapy, usually radiation therapy.

This article discusses common treatments for ACC as well as important post-treatment therapies and follow-up.

Cancer Stem Cells In Adenoid Cystic Carcinoma

Cancer Stem Cells constitute a small fraction of the entire tumor cell population . These cells are highly tumorigenic, capable of self-renewal, and capable of generating the various cell phenotypes that make up a tumor . It has been suggested that CSCs are resistant to conventional chemotherapy and are strongly associated with recurrence and metastasis . Methods for identifying CSCs have been suggested in various types of carcinoma, and the markers identified for labeling differ depending on the type of carcinoma. In a study using a PDX model of ACC, when ALDHhigh and ALDHlow cell populations were subcutaneously injected into mice, ALDHhigh cell populations were capable of forming tumors with a smaller number of cells than ALDHlow cells. This suggested that ALDHhigh cells have high tumorigenicity, and that ALDH is an effective CSC marker in ACC . In another study, when the ALDHhighCD44high and ALDHlowCD44low cells were compared for tumorigenicity, the ALDHhighCD44high cells were more tumorigenic. From this, it was suggested that CD44 in addition to ALDH can be a marker for CSCs in ACC . It has further been reported that CD44 and CD133 have overlapping expression in ACC, suggesting that CD133 may also serve as a marker to identify ACC CSCs .

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Papers Of Particular Interest Published Recently Have Been Highlighted As: Of Importance Of Major Importance

  • Ellington CL, Goodman M, Kono SA, Grist W, Wadsworth T, Chen AY, et al. Adenoid cystic carcinoma of the head and neck: incidence and survival trends based on 1973-2007 surveillance, epidemiology, and end results data. Cancer. 2012 118:444451. .

  • Article PubMed

  • Ho AS, Ochoa A, Jayakumaran G, Zehir A, Valero Mayor C, Tepe J et al. Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma. J Clin Invest. 2019 129:4276-89. doi:10.1172/jci128227. Genomic analysis of 1045 ACCs identified R/M disease is associated with higher rates of NOTCH activating mutations and suggested molecular classification for ACC based on MYB, NOTCH, and TERT status.

  • Ferrarotto R, Mitani Y, McGrail DJ, Li K, Karpinets TV, Bell D et al. Proteogenomic analysis of salivary adenoid cystic carcinomas defines molecular subtypes and identifies therapeutic targets. Clin Cancer Res. 2021 27:852-64. doi:10.1158/1078-0432.Ccr-20-1192. This study suggested two molecular subtypes of ACC tumors, ACC-I and ACC-II, through unsupervised clustering of RNA and proteomics each subtype has distinct disease biology and prognosis.

  • Chen AM, Garcia J, Bucci MK, Chan AS, Kaplan MJ, Singer MI, et al. Recurrent salivary gland carcinomas treated by surgery with or without intraoperative radiation therapy. Head Neck. 2008 30:29. .

  • CAS Article PubMed PubMed Central

  • CAS Article PubMed

  • CAS Article PubMed

  • Article PubMed

  • Article PubMed

  • Histopathology Of Adenoid Cystic Carcinoma

    Adenoid cystic carcinoma of skin (AIP France 2021 – bonus case) dermpath dermatology pathology

    ACC is subdivided into 3 histological groups based on solid components of the tumor including cribriform, tubular, and solid. Cribriform and tubular ACCs usually exhibit a more indolent course, whereas the solid subtype is associated with worse prognosis . Szanto et al. demonstrated that grade III ACC, which displayed marked predominance of the solid portion, resulted in larger tumors that recurred more frequently and had lower cumulative survival rate compared with the other groups . Solid histology has been associated with higher somatic mutation frequency, as well as particular chromosomal and genetic markers including loss of 14q and alterations in the PI3K pathway . In addition, several factors have been associated with disease recurrence including solid type histology, higher histological grade, pathologic stage, and tumor size .

    ACC consists of two different cell types: inner luminal epithelial cells and outer myoepithelial cells. Previous studies have demonstrated that each cell line tends to express different molecular biomarkers. In particular, epithelial cells express c-kit, cox-2 and Bcl-2, while myoepithelial cells express EGFR and MYB. This discrepancy is likely important in understanding the heterogeneity of ACC, including tumor etiology and various responses to current treatments .

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    Newly Detected Genetic Mutations Through Genome Sequencing

    The recent whole exome and genome sequencing of ACC has led to new compelling discoveries. Ho et al. analyzed sequences of 60 ACC tumors paired with normal DNA samples. The goal was to discover driver genes, which revealed genomic alterations in the pathways associated with MYB/MYC, chromatin remodeling, tyrosine kinase signaling, and DNA damage/checkpoint signaling .

    Interestingly, a significant portion of ACC cells did not exhibit MYB involvement, which implicated new potential mechanisms in disease pathogenesis . In line with this, multiple mutations in chromatin regulators were found in 35% of ACC tumors by this genomic sequencing . For example, SMARCA2 was one of the genes found to be mutated in ACC. This gene participates in gene transcription by encoding a DNA dependent ATPase of the mammalian SWI/SNF chromatin remodeling complex . Though mutations in SMARCA2 are reported in a rare developmental disorder , the gene has not yet been directly related to any specific cancer . This may suggest that mutations in SMARCA2 could be involved in ACC tumorigenesis. Other mutated genes associated with gene transcription include SMARCE1, ATRX and ARID1A .1). However, the importance of these mutations in ACC remains undefined.

    Genetic Alterations Related To Myeloblastosis Oncogene

    Multiple studies have been conducted to discover genetic mutations and biomarkers specific for ACC. Among them, a balanced translocation of the v-myb avian myeloblastosis viral oncogene homolog-nuclear factor I/B is considered to be a signature molecular event of ACC oncogenesis. A 2009 study by Persson et al., reported recurrent episodes of MYB-NFIB fusion genes in ACC specimens . The chromosomal translocation t produced chimeric transcripts containing MYB and NFIB and caused deregulation of the MYB gene. As a result, genes targeted by MYB were activated constitutively, resulting in downstream dysregulation of critical cellular mechanisms involved in apoptosis, cell adhesion, and cell cycle regulation .

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    Recurrence And Salvage Treatments

    Throughout the observation period, 35 of 50 cases who underwent radical treatments recurred. In the study of the first recurrent sites, 15 cases had locoregional recurrence , 18 had distant metastatic recurrence, and 2 had both local and distant metastatic recurrence. Throughout the observation period, overall locoregional recurrence was observed in 24 cases , and overall distant metastatic recurrence was seen in 28 cases . Major first distant metastatic sites of the 34 cases that showed distant metastasis throughout the observation period were lung in 27 cases , bone in 6 , and liver in 4 . Lung metastasis was also observed simultaneously in 1 case of bone metastasis and 3 cases of liver metastasis. The overall distant metastatic sites observed throughout the observation period showed only a slight increase in lung metastasis up to 29 cases , but a large increase in bone up to 10 cases and in liver up to 9 cases . Lung was the most common first distant metastatic site, followed by bone and liver, and both bone and liver metastases tended to increase over time.

    Salvage treatments for initial locoregional recurrence in 24 cases of overall locoregional recurrence were as follows: surgery in 10 cases radiotherapy), particle-beam therapy in 4 , radiotherapy in 3, CyberKnife in 1, and BSC in 7. DSS after salvage treatment was significantly better in the salvage-surgery group than in the other-treatment groups .

    Fig. 4

    Immunotherapy And Cancer Stemness


    Emerging evidence suggests the possibility of developing anti-CSC vaccines. Cancer therapeutic vaccines activate a number of tumor antigen-specific cytotoxic T lymphocytes to eliminate the tumor by recognizing tumor-associated antigens . Studies using the xenograft model of ovarian cancer have shown that the CD117+CD44+ CSC vaccine inhibits tumorigenicity . A clinical trial of a MYB-targeted vaccine is being conducted in MYB-expressing tumors, such as ACC and colorectal cancer . The results of this trial should shed light on the therapeutic potential of this new treatment modality.

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    What Is Stereotactic Radiosurgery Boost

    A stereotactic radiosurgery boost is when radiation therapy is given by way of a beam of radiation that penetrates your skin without making any incisions or cuts, targeting a small area. The procedure is done in a clinical setting and requires someone to take you home afterward.

    Stereotactic radiosurgery boost side effects include:

    • Fatigue
    • Skin irritation at the treatment site
    • Hair loss at the treatment site
    • Headache
    • Neurological symptoms, such as seizure, numbness/tingling, or weakness
    • Gastrointestinal symptoms, such as nausea, vomiting, or diarrhea

    Metastatic Acc Treatment Options

    When cancer has spread to other organs , the main treatment includes different types of systemic therapies:

    • Chemotherapy
    • Targeted agents
    • Hormonal treatments

    Sometimes loco-regional approaches or site-specific approaches may be used in conjunction with systemic treatments for palliative purposes . Examples of loco-regional treatments include classical radiation therapy or newer techniques, including proton radiation therapy.

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    Remission And The Chance Of Recurrence

    A remission is when cancer cannot be detected in the body and there are no symptoms. This may also be called having no evidence of disease or NED.

    A remission may be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back. While many remissions are permanent, it is important to talk with your doctor about the possibility of the cancer returning. Understanding your risk of recurrence and the treatment options may help you feel more prepared if the cancer does return. Learn more about coping with the fear of recurrence.

    If the cancer returns after the original treatment, it is called recurrent cancer. It may come back in the same place, meaning it is a local recurrence, or nearby, which is a regional recurrence. If it comes back in another place, it is a distant recurrence.

    When this occurs, a new cycle of testing will begin again to learn as much as possible about the recurrence. After this testing is done, you and your doctor will talk about the treatment options. Often the treatment plan will include the treatments described above, such as surgery and radiation therapy, but they may be used in a different combination or given at a different pace. Your doctor may suggest clinical trials that are studying new ways to treat this type of recurrent cancer. Whichever treatment plan you choose, palliative care will be important for relieving symptoms and side effects.

    Epidemiology Of Adenoid Cystic Carcinoma

    How to treat adenoid cystic carcinoma

    Adenoid cystic carcinoma is a rare cancer most often occurring in the salivary glands. For head and neck ACC, the age-adjusted incidence rate is 4.5 cases per 100,000 individuals, occurring with a slight female predominance . The cancer can also arise in other locations including the breast, skin, respiratory system, and reproductive organs . The mean age at diagnosis of head and neck ACC is approximately 57 years, which varies based on primary cancer site . ACC is characterized by an indolent clinical course and has a tendency for delayed recurrence and metastasis after initial treatment . Five, ten, and fifteen-year survival rates after surgical resection have been reported as 77.3%, 59.6%, and 44.9%, respectively, with almost half of patients dying from ACC, as opposed to other causes, at long-term follow-up . Because of its rarity and distinctive clinical features, the pathophysiology of ACC remains understudied, resulting in fewer evidence-based therapies compared to other cancers.

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    Survival Rates And Clinical Outcomes

    Overall survival , disease-specific survival , locoregional recurrence-free survival , distant metastasis-free survival , and disease-free survival of the whole population are shown in Fig. . Five-year, 10-year, 15-year, 20-year, and 25-year OS rates were 74.0, 63.7, 41.0, 27.3, and 20.0%, respectively. Similarly, DSS rates were 76.3, 65.7, 51.2, 51.2, and 38.4%, respectively LRFS rates were 62.5, 44.2, 16.9, 16.9, and 16.9%, respectively DMFS rates were 52.0, 35.1, 19.9, 13.3, and 13.3%, respectively and DFS rates were 45.1, 25.2, 9.4, 9.4, and 9.4%, respectively. OS and DSS almost overlapped for more than 10years after starting observation the difference began to increase beyond 5% after 144.1months , and it finally became 18.4% at 300months . Of all 7 cases of intercurrent-disease deaths observed during the observation period, 5 died of other cancers , and 2 died of pneumonia . After the longest disease-free interval was observed at the time point of 169.9months , the DFS reached a plateau, and the eventual 25-year DFS was 9.4%. On the other hand, 25-year DSS was 38.4%, which differed largely from DFS. Of all the 10 long-term-surviving cases beyond 12.0years, when the difference between the DSS and OS started to be observed, 1 died of ACC , 5 were alive , and 4 died of intercurrent disease . While intercurrent-disease deaths increased as time advanced, 60% of long-term surviving cases were eventually in an ACC tumor-bearing state.

    Fig. 1

    What Are The Signs And Symptoms Of Adenoid Cystic Carcinoma Of Lung

    Adenoid Cystic Carcinoma of Lung may present the following signs and symptoms:

    • ACC is a slow-growing and painless tumor with a potential to invade into the surrounding tissues. In many individuals, often no significant signs and symptoms are seen for many months and years
    • The tumor develops slowly and the growth rate varies from one individual to another. Often individuals have tumors growing for 5 years or more, after which they may present symptoms
    • An unpredictable growth pattern is recognized the tumor grows slowly during the initial stages, but a sudden rapid growth may be visible after a certain time duration
    • The tumor infiltrates into the surrounding nerves and can cause pain, numbness, and tingling sensations
    • The adenoid cystic carcinoma can arise in the following lung parts:
    • Within the bronchial airways, in which case the tumor is known as Bronchial Adenoid Cystic Carcinoma
    • In the lung tissue or lung parenchyma, in which case the tumor is known as Pulmonary Adenoid Cystic Carcinoma
  • Usually a single mass is observed a large mass may cause shortness of breath, blood in sputum, repeated coughing, and chest pain
  • Additional symptoms may include wheezing, hemoptysis , weight loss, and pneumonia due to airways obstruction
  • Obstructive signs and symptoms are usually caused when the tumor is present in the bronchus. Tumors in the lungs tend to typically remain silent
  • Large tumors may cause a pressure effect by compressing adjoining structures and organs
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