Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• When patients are told they have a variant of unknown significance (VUS):
  • It can often lead to anxiety and overtreatment
• It is important to counsel patients that a VUS:
  • Is not clinically actionable and the majority of VUS are reclassified as benign
• Patients should be counseled to update their genetic counselors:
  • As their family history changes and keep contact information up to date as variant reclassification does occur
• The American College of Medical Genetics has recommended that genetic testing classify genetic variants using the following classification schema: 
  • Deleterious (pathogenic)
  • Suspected deleterious (likely pathogenic)
  • Variant of Uncertain Clinical Significance
  • Genetic variant, favor polymorphism (likely benign)
  • Polymorphism (benign)
• While deleterious and suspected deleterious BRCA mutations:
  • Are known to be associated with an increased risk of breast and ovarian cancer:
    • Among breast cancer patients:
      • It is estimated that 2% to 6% carry a BRCA 1 / 2 mutation
    • Among epithelial ovarian cancer patients:
      • It is estimated that 10% to 15% carry a BRCA 1 / 2 mutation
    • The lifetime risk of breast cancer for BRCA 1 / BRCA 2 mutation carriers:
      • Is approximately 45% to 80%
    • The lifetime ovarian cancer risk is:
      • 45% to 60% for BRCA 1 mutation carriers
      • 11% to 35% for BRCA 2 mutation carriers
• It is unknown whether a BRCA VUS mutation:
  • Is associated with an increased risk due to limited available data
• As the use of genetic testing increases and as more of the population is tested:
  • The knowledge base regarding variant pathogenicity constantly grows
• Given the amount of data available from many years of BRCA 1 / 2 testing:
  • The prevalence of VUS among this population has declined to 2% to 5%:
    • However, among moderate and low penetrance genes:
      • The number of VUS continues to rise
• As the data expand and knowledge regarding a variant evolves:
  • A variant may be reclassified:
    • In a recent study reported in the Journal of the American Medical Association:
      • 25.4% of patients initially diagnosed with a VUS were reclassified over a 12-year period:
        • Of these patients, 97% were downgraded to benign or likely benign
        • Three percent of patients were upgraded to pathogenic or likely pathogenic variants
        • Given this low risk of reclassification to pathogenic mutation:
          • Risk-reducing mastectomy, salpingo-oophorectomy, or genetic testing of family members are not indicated for this patient
  • There is currently no established effective screening protocol for pancreatic cancer, even among patients with a deleterious BRCA 2 mutation
• References
  • Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424.
  • Hall MJ, Reid JE, Burbidge LA, Pruss D, Deffenbaugh AM, Frye C, et al. BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer. Cancer. 2009;115(10):2222-2233.
  • Mersch J, Brown N, Pirzadeh-Miller S, Mundt E, Cox HC, Brown K, et al. Prevalence of variant reclassification following hereditary cancer genetic testing. JAMA. 2018;320(12):1266-1274.

#Arrangoiz #CancerSurgeon #BreastSurgeon #SurgicalOncologist #BreastCancer #BRCAMutation #CASO #CenterforAdvancedSurgicalOncology #PalmettoGeneralHospital

👉Expert Panel on Radiation Oncology – Head & Neck Cancer: Joseph K. Salama, MD; Nabil Saba, MD; Harry Quon, MD, MS; Jonathan J. Beitler, MD; Madhur Kumar Garg, MD; Joshua Lawson, MD; Mark W. McDonald, MD7; John A. Ridge, MD, PhD; Richard V. Smith, MD; Anamaria Reyna Yeung, MD1; Sue S. Yom, MD.

👉Introduction

1. The standard definitive treatment of locoregionally advanced squamous cell cancer of the head and neck (SCCHN) is either concurrent chemoradiotherapy (CRT) or appropriate surgical resection followed by adjuvant therapy directed by pathologic risk factors.

2. However, local or regional recurrences and distant metastases remain frequent after surgical treatment of stage III or IV disease.

3. Radiation therapy (RT) is added to surgery to decrease locoregional failure.

4. Adjuvant RT has been shown to improve locoregional control compared to neoadjuvant RT in a multi-institutional randomized trial.
5. Postoperative RT (PORT) has traditionally been given for most patients with potentially resectable stages III, IVa, and IVb SCCHN with the goal of maximizing cure and maintaining organ function.
6. Following PORT, locoregional control is 69% to 72%, and 5-year survival rates approach 30% to 40%.
7. This has prompted interest in adding chemotherapy to surgery and RT to improve outcome.
8. The addition of concurrent chemotherapy to adjuvant RT has been shown to result in improved locoregional control, disease-free survival (DFS), and/or overall survival (OS) rates for selected SCCHN patients.
B. Role of Postoperative Radiation Therapy
1. The addition of PORT became an accepted treatment following the publication of results from the MD Anderson Cancer Center (MDACC) which demonstrated that adjuvant RT decreased recurrence.
2. The Radiation Therapy Oncology Group (RTOG) 73-03 trial randomized 320 (T2 to T4, N any) head and neck cancer patients to 50 Gy preoperatively versus 60 Gy postoperatively.
– The 10-year locoregional control was significantly improved in the postoperatively treated patients (70% vs 58%).
– OS was not different between the groups due to deaths from distant metastases and second primary cancers.
3. Further evidence supporting the role of adjuvant RT includes an analysis by the Surveillance, Epidemiology and End Results (SEER) program of node-positive head and neck cancer patients reporting an absolute 10% overall and cause-specific survival benefit at 5 years.
– All nodal stages and primary sites (except oral cavity) had improved 5-year OS rates following PORT compared to patients who did not receive PORT.
– Additionally, within a randomized study of postoperative patients, a prospective cohort of nonrandomized low-pathologic-risk postoperative patients was observed.
= Compared to patients with intermediate pathologic risk treated with PORT, the low-risk group had comparable, if not worse locoregional control.
= Finally, a small randomized study of buccal mucosa patients demonstrated a DFS benefit to PORT compared to surgical resection alone.
C. High-risk pathologic features were initially defined by two large analyses.
1. A post-hoc analysis of a randomized study of SCCHN patients treated at the MDACC demonstrated that extranodal extension was an independent predictor of recurrence, and that two or more involved lymph nodes trended toward worse locoregional recurrence.
2. These factors (ENE and two or more positive lymph nodes) were validated in a combined analysis of postoperative RTOG studies:
– RTOG 85-03 testing the addition of cisplatin prior to PORT and RTOG 88-24 testing the addition of concurrent cisplatin to PORT were reanalyzed to determine the importance of different pathologic features on risk of recurrence.
= Patients treated on the RTOG 85-03 were stratified into three post-hoc groups:
= Group 1 included those with no more than two pathologically involved lymph nodes, no extracapsular spread (ECS), and uninvolved surgical margins
= Group 2 included patients with two or more pathologically involved lymph nodes or extranodal extension and surgically uninvolved margins
= Group 3 included patients with microscopically involved surgical margins.
= These risk stratifications resulted in significant differences in 5-year locoregional recurrence rates: 17%, 27%, and 67% in groups 1, 2, and 3, respectively.
= Furthermore, median survival times were different among the three groups, being 5.6 years in group 1, 2.6 years in group 2, and 1.5 years in group 3.
D. Timing of PORT:
1. When PORT is delivered without chemotherapy, the combination of surgical resection and PORT should be considered as a treatment package.
2. Completion of the treatment package in as short a time as possible has been associated with improved locoregional control and survival rates, which are likely related to tumor repopulation effects.
3. The strongest evidence favoring completion of surgery and PORT within a tight schedule comes from a trial at the MDACC randomizing 213 patients to a tailored therapy based on their respective risk factors:
– Patients with no pathologic risk features received no PORT
– Those in the intermediate-risk group (n = 31) received 57.6 Gy over 6.5 weeks
– Those in the high-risk group were randomized to receive either 63 Gy over 5 weeks (n = 76) or 7 weeks (n = 75).
– For high-risk patients, completion of the entire treatment package in less than 11 weeks was associated with improved actuarial 5-year locoregional control (76%) compared to packages of 11 to 13 weeks duration (62%) and greater than 13 weeks duration (38%) (P=0.002).
– Although a statistically significant OS benefit defined as a P value < 0.05 was not seen, patients receiving accelerated PORT over 5 weeks trended towards improved survival (P=0.08) and locoregional control (P=0.11).
= Some single institution retrospective analyses support this finding while others do not.
= Confounding these analyses is the fact that potentially larger tumors with high-risk features required larger more complex operations with potentially longer recovery times, which may influence the initiation of PORT.
4. When PORT is delivered with concurrent chemotherapy, the impact of time to completion of treatment is presently unknown.
– In general, the treatment should be completed in as short a time frame as possible when patients have adequately healed from their surgical wounds.
– However, when the RTOG examined the addition of postoperative paclitaxel followed by radiation concurrent with paclitaxel and cisplatin, there was a noted improvement in locoregional control rates and survival when compared to historical controls.
= Therefore, whether the timing of PORT affects outcomes in the setting of concurrent chemotherapy is not clear.

American College of Radiology ACR Appropriateness Criteria ADJUVANT THERAPY FOR RESECTED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
Expert Panel on Radiation Oncology – Head & Neck Cancer: Joseph K. Salama, MD; Nabil Saba, MD; Harry Quon, MD, MS; Jonathan J. Beitler, MD; Madhur Kumar Garg, MD; Joshua Lawson, MD; Mark W. McDonald, MD7; John A. Ridge, MD, PhD; Richard V. Smith, MD; Anamaria Reyna Yeung, MD1; Sue S. Yom, MD.
A. Introduction:
1. The standard definitive treatment of locoregionally advanced squamous cell cancer of the head and neck (SCCHN) is either concurrent chemoradiotherapy (CRT) or appropriate surgical resection followed by adjuvant therapy directed by pathologic risk factors.
2. However, local or regional recurrences and distant metastases remain frequent after surgical treatment of stage III or IV disease.
3. Radiation therapy (RT) is added to surgery to decrease locoregional failure.
4. Adjuvant RT has been shown to improve locoregional control compared to neoadjuvant RT in a multi-institutional randomized trial.
5. Postoperative RT (PORT) has traditionally been given for most patients with potentially resectable stages III, IVa, and IVb SCCHN with the goal of maximizing cure and maintaining organ function.
6. Following PORT, locoregional control is 69% to 72%, and 5-year survival rates approach 30% to 40%.
7. This has prompted interest in adding chemotherapy to surgery and RT to improve outcome.
8. The addition of concurrent chemotherapy to adjuvant RT has been shown to result in improved locoregional control, disease-free survival (DFS), and/or overall survival (OS) rates for selected SCCHN patients.
B. Role of Postoperative Radiation Therapy
1. The addition of PORT became an accepted treatment following the publication of results from the MD Anderson Cancer Center (MDACC) which demonstrated that adjuvant RT decreased recurrence.
2. The Radiation Therapy Oncology Group (RTOG) 73-03 trial randomized 320 (T2 to T4, N any) head and neck cancer patients to 50 Gy preoperatively versus 60 Gy postoperatively.
– The 10-year locoregional control was significantly improved in the postoperatively treated patients (70% vs 58%).
– OS was not different between the groups due to deaths from distant metastases and second primary cancers.
3. Further evidence supporting the role of adjuvant RT includes an analysis by the Surveillance, Epidemiology and End Results (SEER) program of node-positive head and neck cancer patients reporting an absolute 10% overall and cause-specific survival benefit at 5 years.
– All nodal stages and primary sites (except oral cavity) had improved 5-year OS rates following PORT compared to patients who did not receive PORT.
– Additionally, within a randomized study of postoperative patients, a prospective cohort of nonrandomized low-pathologic-risk postoperative patients was observed.
= Compared to patients with intermediate pathologic risk treated with PORT, the low-risk group had comparable, if not worse locoregional control.
= Finally, a small randomized study of buccal mucosa patients demonstrated a DFS benefit to PORT compared to surgical resection alone.
C. High-risk pathologic features were initially defined by two large analyses.
1. A post-hoc analysis of a randomized study of SCCHN patients treated at the MDACC demonstrated that extranodal extension was an independent predictor of recurrence, and that two or more involved lymph nodes trended toward worse locoregional recurrence.
2. These factors (ENE and two or more positive lymph nodes) were validated in a combined analysis of postoperative RTOG studies:
– RTOG 85-03 testing the addition of cisplatin prior to PORT and RTOG 88-24 testing the addition of concurrent cisplatin to PORT were reanalyzed to determine the importance of different pathologic features on risk of recurrence.
= Patients treated on the RTOG 85-03 were stratified into three post-hoc groups:
= Group 1 included those with no more than two pathologically involved lymph nodes, no extracapsular spread (ECS), and uninvolved surgical margins
= Group 2 included patients with two or more pathologically involved lymph nodes or extranodal extension and surgically uninvolved margins
= Group 3 included patients with microscopically involved surgical margins.
= These risk stratifications resulted in significant differences in 5-year locoregional recurrence rates: 17%, 27%, and 67% in groups 1, 2, and 3, respectively.
= Furthermore, median survival times were different among the three groups, being 5.6 years in group 1, 2.6 years in group 2, and 1.5 years in group 3.
D. Timing of PORT:
1. When PORT is delivered without chemotherapy, the combination of surgical resection and PORT should be considered as a treatment package.
2. Completion of the treatment package in as short a time as possible has been associated with improved locoregional control and survival rates, which are likely related to tumor repopulation effects.
3. The strongest evidence favoring completion of surgery and PORT within a tight schedule comes from a trial at the MDACC randomizing 213 patients to a tailored therapy based on their respective risk factors:
– Patients with no pathologic risk features received no PORT
– Those in the intermediate-risk group (n = 31) received 57.6 Gy over 6.5 weeks
– Those in the high-risk group were randomized to receive either 63 Gy over 5 weeks (n = 76) or 7 weeks (n = 75).
– For high-risk patients, completion of the entire treatment package in less than 11 weeks was associated with improved actuarial 5-year locoregional control (76%) compared to packages of 11 to 13 weeks duration (62%) and greater than 13 weeks duration (38%) (P=0.002).
– Although a statistically significant OS benefit defined as a P value < 0.05 was not seen, patients receiving accelerated PORT over 5 weeks trended towards improved survival (P=0.08) and locoregional control (P=0.11).
= Some single institution retrospective analyses support this finding while others do not.
= Confounding these analyses is the fact that potentially larger tumors with high-risk features required larger more complex operations with potentially longer recovery times, which may influence the initiation of PORT.
4. When PORT is delivered with concurrent chemotherapy, the impact of time to completion of treatment is presently unknown.
– In general, the treatment should be completed in as short a time frame as possible when patients have adequately healed from their surgical wounds.
– However, when the RTOG examined the addition of postoperative paclitaxel followed by radiation concurrent with paclitaxel and cisplatin, there was a noted improvement in locoregional control rates and survival when compared to historical controls.
= Therefore, whether the timing of PORT affects outcomes in the setting of concurrent chemotherapy is not clear.

• Screening mammography:
  • Is important in identifying breast cancer at an early stage:
• Calcifications have many forms:
  • The characteristics of the calcifications help identify whether they are associated with a benign or malignant process:
    • Smooth, round, large and layering calcium:
      • Are generally associated with benign findings
    • Fine, irregular, punctate, linear and branching, and pleomorphic calcifications:
      • Are characteristics generally associated with malignant findings
• Magnification views of the calcifications:
  • Are essential in helping to evaluate the calcifications to determine the appearance and to be able to accurately interpret the findings

• References:
  • Brant W, Helms C. Fundamentals of Diagnostic Radiology, 5th Edition. Lippincott, Williams & Wilkins; 2019
  • Baldwin P. Breast calcification imaging. Radiol Technol. 2013;84(4):383M-404M.

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncology #CASO #CenterforAdvancedSurgicalOncology #PalmettoGeneralHospital

• The benefit of chemotherapy among women with early-stage, hormone-receptor positive breast cancers has become largely determinant on the use of gene expression profiles, including Oncotype DX, MammaPrint, and PAM50. Oncotype DX score is a 21-gene assay that uses RT-PCR to calculate recurrence risk using a scoring system from 0 to 100, and categorizes women into low, intermediate, and high risk of recurrence based on pre-specified cut points. MammaPrint is a 70-gene assay performed with microarray, and classifies tumors as having good vs poor prognostic signatures. PAM50 tests 50 classifier genes and categorizes women by intrinsic subtypes including luminal A, luminal B, HER2-enriched, basal-like and normal-like. Adjuvant! Online is an online program that uses standard clinicopathologic variables to estimate survival for breast cancer patients treated by local therapy alone and the survival and disease-free survival benefit gained by the addition of systemic adjuvant therapy.

REFERENCES

1. Paik S. Is gene array testing considered to be routine now? Breast. 2011;20 Suppl 3:S87-S91.
2. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817-2826.
3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines for Oncology: Breast Cancer. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp Published January 2016. Accessed January 31, 2017.

• In 2020, an estimated 276,480 new cases of invasive breast cancer will be diagnosed in women in the U.S. as well as 48,530 new cases of non-invasive (in situ) breast cancer.
• 64% of breast cancer cases are diagnosed at a localized stage (there is no sign that the cancer has spread outside of the breast), for which the 5-year survival rate is 99%.
• This year, an estimated 42,170 women will die from breast cancer in the U.S.
• Although rare, men get breast cancer too. In 2020, an estimated 2,620 men will be diagnosed with breast cancer this year in the U.S. and approximately 520 will die.
• 1 in 8 women in the United States will be diagnosed with breast cancer in her lifetime
• Breast cancer is the most common cancer in American women, except for skin cancers. It is estimated that in 2020, approximately 30% of all new women cancer diagnoses will be breast cancer.
• There are over 3.5 million breast cancer survivors in the United States.
• On average, every 2 minutes a woman is diagnosed with breast cancer in the United States.

#Arrangoiz #CancerSurgeon #BreastSurgeon #SurgicalOncologist #CASO #CenterforAdvancedSurgicalOncology #PalmettoGeneralHospital

• The Cancer and Leukemia Group B (CALGB) 9343 trial:
  • Enrolled 647 patients:
    • From 1994 until 1999
  • Long-term follow-up data:
  • Were published in 2013:
    • With a median follow-up of:
      • 12.6 years
    • Women age 70 years or older:
      • With clinical stage I:
        • cT1, cN0, cM0
        • ER-positive breast cancer
        • Treated by lumpectomy 
  • Were randomly assigned to receive:
    • Tamoxifen plus radiation therapy (TamRT) or
    • Tamoxifen alone (Tam)
  • At 10 years:
    • 98% of women:
      • Receiving TamRT were free from local and regional recurrences
    • Compared to 91% of those receiving Tam
    • The 10-year estimates of overall survival (OS) were: o 67% (95% confidence interval [CI], 62–72%) in the TamRT group versus o 66% (95% CI, 61%–71%) in the Tam group:  But the difference was not statistically significant  In addition to concluding that: • While RT (in addition to Tam): o Reduces locoregional recurrence:  The authors noted that “the impact of breast cancer in this select group of older women is much smaller than that of comorbid conditions”: • Only 3% of women in study have died as a result of breast cancer whereas 49% have died as a result of other causes • References: o Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013;31:2382-2389.

• The exact mechanism by which breast cancer is initiated is unknown:
  • However, much effort has been made to molecularly characterize breast cancer and delineate its formation and progression
• At the cell of origin level:
  • The clonal evolution model:
    • In which mutations accumulate
    • Epigenetic changes in tumor cells occur
    • The ‘fittest’ cells survive
  • The cancer stem cell model:
    • In which only the precursor cancer cells:
      • Initiate and sustain progression
  • The clonal evolution model and the cancer stem cell model:
    • Are both implicated, and further complicated by the fact that cancer stem cells may also evolve in a clonal fashion
• At the morphological level:
  • There is a continuum of lesions and genetic modifications from normal glands to cancer
• At the molecular level:
  • There is evidence showing that breast cancer evolves along two divergent molecular pathways of progression:
    • Mainly related to ER expression, and tumor grade and proliferation:
      • Described in the intrinsic classification
    • Furthermore, the identification of breast cancer susceptibility genes:
      • Has shed the light on some aspects of the pathogenesis of both sporadic and inherited breast cancer
    • The first pathway:
      • The low-grade-like pathway — is characterized by gain of 1q, loss 16q, infrequent amplification of 17q12 and a gene expression signature (GES) with a majority of genes associated with the ER phenotype, diploid or near diploid karyotypes and low tumour grade. The luminal A group and to some extent the luminal B group fall into this pathway. The second pathway — the high-grade-like pathway — is charac- terized by loss of 13q, gain of chromosomal region 11q13, amplification of 17q12 (containing ERBB2, encoding HER2) and an expression signature of genes involved in the cell cycle and cellular proliferation61. Tumours composed of intermediate to high grade, including HER2-positive tumours and TNBC, fall into this pathway

• Fibroadenomas:
  • Are benign tumors composed of stromal and epithelial elements
  • That are commonly seen in young women
  • Multiple or complex fibroadenomas:
    • May indicate a slightly increased risk for breast cancer: 
      • The relative risk of breast cancer in patients with such fibroadenomas: 
        • Is approximately twice that of patients of similar age without fibroadenomas 
  • A patient’s age determines the preferred imaging method:
    • In general, ultrasonography (US) is preferred: 
      • If a palpable mass is found 
      • If a patient is younger than 30 years 
      • If the patient is pregnant
    • Mammography and US are both useful if the patient has: 
      • A palpable mass 
      • Is older than 30 years 
      • Is not pregnant o In patients younger than 30 years: 
        • The most appropriate modality is US:
          • Because the patient is spared radiation exposure and because the likelihood for fibroadenoma is not that high
    • Mammography is not indicated as the primary imaging study in women younger than 30 years: 
      • Unless high-risk factors are present
    • Computed tomography (CT) scanning: 
      • Is not initially indicated for assessing a palpable lump in a woman in women younger than 30 years:
        • Because of radiation exposure
        • The inability of CT to demonstrate micro-calcifications
        • The lack of specificity in the findings
    • Magnetic resonance imaging (MRI): 
      • Is not initially indicated for assessing a palpable lump in women younger than 30 year:
        • Mainly because of its high cost and the high likelihood of false-positive finding
    • Positron emission tomography: 
      • Is expensive and is not universally available
• On mammograms:
  • Fibroadenomas typically appear as:
    • Circumscribed oval or round masses:
      • Which occasionally have coarse calcifications
• On ultrasonograms:
  • Fibroadenomas appear as circumscribed, homogeneous, oval, hypoechoic masses:
    • That may have gentle lobulations 
    • A smooth, thin, echogenic capsule 
    • Variable acoustic enhancement; and homogeneity
• On MRI:
  • Fibroadenomas typically appear as smooth masses with high signal intensity on T2-weighted images and enhancement with the administration of gadolinium-based contrast agent
• Fibroadenoma:
  • Is a common benign breast lesion: 
    • Results from the excess proliferation of connective tissue
    • Fibroadenomas characteristically contain both: 
      • Stromal and epithelial cells
• Epidemiology:
  • They usually occur in women: 
    • Between the ages of 10 and 40 years
    • It is the most common breast mass: 
      • In the adolescent and young adult population
    • Their peak incidence is between: 
      • 25 and 40 years
    • The incidence decreases after 40 years
    • Fibroadenomas commonly enlarge during pregnancy and involute at menopause: • Hence, they rarely present after the age of 40 years o The lesions are well defined and well-circumscribed clinically and the overlying skin is normal o The lesions are not fixed to the surrounding parenchyma and slip around under the palpating fingers:  Hence the colloquial term a breast “mouse”. • Pathology: o A fibroadenoma is a type of adenomatous breast lesion:  It contains epithelium  Has minimal malignant potential o Multiple fibroadenomas occur in:  10% to 15% of patients: • Patients with multiple fibroadenomas: o Tend to have a strong family history of these tumors o They are assumed to be:  Aberrations of normal breast development (ANDI) or the product of hyperplastic processes: • Rather than true neoplasms o Fibroadenomas can be stimulated by estrogen and progesterone o Some fibroadenomas also have receptors and respond to:  Growth hormone and epidermal growth factor o When found in an adolescent girl:  The term juvenile fibroadenoma is more appropriate • Location: o Although they can be located anywhere in the breast:  There may be a predilection for the upper outer quadrant • Associations: o Cyclosporin use o Cowden syndrome • Radiographic features: o Mammography:  Fibroadenomas have a spectrum of features: • Well-circumscribed discrete oval mass hypodense or isodense to the breast glandular tissue • Mass with macro-lobulation or partially obscured margin • Involuting fibroadenomas in older, typically postmenopausal patients may contain: o Calcification:  Often producing the classic, coarse popcorn calcification appearance  In some cases the whole lesion is calcified  Calcification may also present as crushed stone-like micro-calcification which makes differentiation from malignancy difficult • Breast ultrasound: o Typically seen as a well-circumscribed, round to ovoid, or macro-lobulated mass with generally uniform hypoechogenicity o Intralesional sonographically detectable calcification:  May be seen in approximately 10% of cases o Sometimes a thin echogenic rim (pseudo capsule) may be seen sonographically • Breast MRI: o T1: typically hypo intense or isointense compared with adjacent breast tissue o T2: can be hypo- or hyper intense o T1 C+ (Gd): can be variable but a majority will show slow initial contrast enhancement followed by a persistent delayed phase (type I enhancement curve); non-enhancing internal septations may be seen • Diagnosis: o These lesions are easily biopsied under ultrasound guidance o When a lesion has the typical features of a fibroadenoma on ultrasound and there are no clinical red flags:  They can be safely followed clinically o When lesions enlarge or have atypical imaging findings:  Ultrasound-guided core biopsy is a minimally invasive outpatient procedure that will give a diagnosis with virtually no complications o There may be a maximum diameter above which a biopsy should be done if no previous imaging is available:  The reason for intervention based on size is that a phyllodes tumor may be indistinguishable from a fibroadenoma on ultrasound: • A maximum diameter of 2.5 cm may be a useful benchmark for biopsy if you have no previous imaging o Interval enlargement is an indication for biopsy • Treatment and prognosis: o They are benign lesions with minimal or no malignant potential o The risk of malignant transformation is extremely low:  Has been reported to range around 0.0125% to 0.3%. o Indications for biopsy include:  Enlarging lesion  Atypical findings on ultrasound  A lesion above 2.5 cm and there are no previous studies for comparison  Patient peace of mind: • Some patients are simply not happy with a palpable mass in the breast without a histological diagnosis: o This is a valid and reasonable indication for biopsy

👉Surgical site infection is a rare complication after routine transcervical thyroidectomy, with a reported incidence of 0.09% to 2%.

👉In a small European study, preoperative antibiotic administration did not affect the incidence of surgical site infection.

👉Antimicrobial prophylaxis (AMP) for clean surgery of the head and neck was not recommended in a 1999 pharmacy guideline, with moderate strength of evidence.

👉A recent single-institution randomized trial confirmed the safety of clean thyroid and parathyroid surgery without AMP.

👉However, routine AMP is still commonly used for clean thyroid and parathyroid surgeries in Japan and many other countries; according to an international survey of 275 endocrine surgeons, 26% administered AMP “almost always”, particularly in Asia (59%).

👉Because both preoperative (obesity, alcohol use) and intraoperative factors (ie, operative time, airway injury) are associated with infection, high-risk patients may benefit from selective use of AMP, in which case gram-positive coverage should be administered before or on induction.

👉With rare exceptions, postoperative AMP is not indicated.

👉Recommendation 19 AAES: Antimicrobial prophylaxis is not necessary in most cases of standard transcervical thyroid surgery. (Strong recommendation, high-quality evidence)

#Arrangoiz #ThyroidSurgeon #ParathyroidSurgeon #HeadandaneckSurgeon #EndocrineSurgery #CASO #CenterforAdvancedSurgicalOncology #PalmettoGemeralHospital

👉REFERENCES

#Arrangoiz

#BreastSurgeon

#CancerSurgeon