Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

Diagnostic Thyroid Testing: Serum Thyroid Stimulating Hormone (TSH)

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Thyroid Stimulating Hormone (TSH):
    • Is produced from the anterior pituitary gland:
      • After stimulation by thyrotropin-releasing hormone (TRH)
  • Thyrotropin-releasing hormone (TRH):
    • Is a modified three-amino acid peptide:
      • Produced by neurons of the paraventricular nucleus:
        • In the hypothalamus
    • TRH signaling from the hypothalamus:
      • Is achieved through a portal venous system:
        • Located in the infundibulum of the pituitary stalk:
          • Which allows communication to the pituitary gland
  • Both TRH and TSH gene expression:
    • Are decreased by excess thyroid hormone levels:
      • Via negative feedback mechanisms (Figure)
    • Both the hypothalamus and pituitary:
      • Have high levels of 5′deiodinases Type 2 enzyme (Dio2):
        • Catalyzes the removal of the 5′ iodine from the outer ring of thyroxine (T4):
          • To create the metabolically active triiodothyronine (T3)
        • So T4 levels are the primary feedback:
          • T4 is converted locally to T3:
            • Which suppresses TRH and TSH gene expression
Schematic Representation of Control of Thyroid-Stimulating Hormone (TSH) Secretion by the Thyrotroph Cells in the Anterior Pituitary Gland.
High concentrations of T3 suppress TSH release, and low concentrations enhance the expression of TSH. Thyrotropin-releasing hormone (TRH) also stimulates TSH release, and its absence results in failure of the thyrotroph to release TSH, resulting in hypothyroidism. TRH is secreted by neurons in the paraventricular nuclei in the hypothalamus and reaches the anterior pituitary via the hypothalamic hypophyseal portal venous system. TSH travels through the circulatory system to stimulate the thyroid and to produce thyroid hormones T4 and T3. By negative feedback inhibition, the circulating thyroid hormones suppress the production and excretion of TRH and TSH to bring the system back into equilibrium to maintain tight control over circulating thyroid hormone levels.
  • Pituitary TSH is secreted in a pulsatile manner:
    • Higher levels at night and lower levels during the day:
      • The inverse of the cortisol cycle
    • Although pulse frequency is increased nocturnally to result in a diurnal variation of TSH concentrations:
      • Levels remain within the reference range
    • Generally, laboratory testing of serum TSH concentrations during daylight hours:
      • Is not substantially affected by the diurnal variation of TSH secretion:
        • But results outside the reference range may occur in euthyroid individuals when drawn outside of these times
  • TSH stimulates the synthesis and release of thyroid hormone from the thyroid gland:
    • TSH production from the anterior pituitary gland is inverse log-linearly regulated by serum thyroid hormone concentrations:
      • When there are small decreases in thyroid hormone levels in circulation:
        • Large increases in serum TSH stimulate thyroid hormone production by the thyroid gland
      • This negative feedback loop between serum TSH and the serum-free thyroid hormones:
        • Is able to maintain circulating thyroid levels within a tight range
  • Serum TSH is the preferred screening test:
    • In the evaluation of thyroid function in the ambulatory patient:
      • Regardless of whether the patient is taking thyroid hormone replacement medication
  • For the healthy patient in an ambulatory setting:
  • The diagnosis of hypothyroidism or hyperthyroidism:
    • May be determined with approximately 98% sensitivity and 92% specificity using serum TSH
    • In addition, TSH has a narrow intraindividual variability of ± 0.5 mIU/L:
      • Such that thyroid dysfunction may be present if there are significant changes in TSH values over time in an individual, even if they remain within the reference range
  • In certain situations, however, such as known or suspected pituitary or hypothalamic dysfunction, recent hyperthyroidism, critical illness, starvation, use of certain medications (dopamine or high-dose glucocorticoids), interference with serum thyroid autoantibodies, and thyroid hormone resistance syndromes:
    • The TSH level is inaccurate for the thyroidal status and should not be used in isolation to determine thyroid function
  • In addition, the presence of interfering heterophile antibodies (antibodies against the animal-derived antibodies used in the immunometric assay):
    • May rarely cause abnormally high or low TSH levels:
      • These conditions should be suspected when the pattern of the TSH levels does not correlate to the clinical presentation or when the peripheral serum hormone levels do not change as expected with elevated or suppressed serum TSH concentrations
  • Serum TSH assays:
    • Have evolved considerably since measurements were first described in the 1960s:
      • When the functional sensitivity was between 1 and 2 mIU/L
    • The commonly used second-generation TSH assays have an improved functional lower limit of 0.10 to 0.20 mIU/L:
      • Which is able to differentiate between euthyroid and hyperthyroid states but does not indicate the degree of hyperthyroidism
    • In contrast, a third-generation TSH assay can detect levels as low as 0.01 to 0.02 mIU/L:
      • This is helpful when there is a challenging pattern of serum thyroid function tests that include an extremely suppressed TSH
    • In the rare instance they are needed, fourth-generation immunochemiluminometric assays are capable of detecting TSH levels in the range of 0.01 to 0.001 mIU/L
  • A serum TSH level measured in an ambulatory population that lies within the reference range:
    • Is generally considered evidence of normal thyroid function and requires no additional testing
    • Reference ranges for serum TSH can vary slightly from one commercial laboratory to another:
      • It should be noted that normal ranges, which are based on the epidemiologic distribution of serum TSH concentrations in healthy populations:
        • From which serum thyroid autoantibody positivity and iodine status (both of which can affect TSH), may be variable
    • If an abnormal screening TSH result is encountered:
      • The circulating thyroid hormone levels should be assessed
        • The specific pattern of tests will allow further insight into whether clinical thyroid dysfunction should be suspected
Evaluation and Management of Hypothyroidism in Individuals With Corresponding Signs and Symptoms.
Evaluation and Management of Hyperthyroidism in Individuals with Corresponding Signs and Symptoms.

Serum Thyroid Autoantibodies

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Hyperthyroidism and hypothyroidism:
    • Are often the result of autoimmune diseases:
      • In which immunoglobulin G (IgG) antibodies:
        • Such as thyroid peroxidase (TPO Ab, previously known as antimicrosomal antibodies), thyroglobulin (Tg Ab), and the TSH receptor (TSHR Ab):
          • Are formed against thyroid proteins
    • The presence of TPOab is commonly associated with patients with hypothyroidism:
      • But can be present in normal individuals who do not display any obvious symptoms of clinical thyroid disease
    • TPOabs are present in approximately 10% of normal individuals:
      • While it was detected in almost 100% of samples of patients with autoimmune hypothyroidism
  • More than 90% of patients with autoimmune thyroid disease (Hashimoto’s thyroiditis and Graves’ disease):
    • Will have elevated titers of second-generation assays for TPO Ab and Tg Ab
  • When biochemical hypothyroidism is found:
    • Measuring TPO Ab can be helpful:
      • Because its result can provide additional information regarding the etiology of the thyroid dysfunction
  • Median serum TSH concentrations are increased within the reference range:
    • Among those with serum TPO Ab and Tg Ab positivity:
      • Compared with those without TPO Ab titers, and are a predictor for the development of biochemical thyroid dysfunction in euthyroid individuals
  • In individuals with subclinical hypothyroidism:
    • Both serum TPO Ab positivity and sonographic characteristics suggestive of chronic thyroiditis:
      • Are associated with an increased likelihood of progression to overt hypothyroidism
  • The TSHR Abs are a group of immunoglobulins:
    • That produce Graves’ hyperthyroidism
    • Measured as:
      • TSH receptor binding, TRAB (TSH-receptor antibody) or in a functional bioassay, thyroid stimulating immunoglobulin (TSI)
    • TSH receptor antibodies:
      • Are being increasingly recommended for monitoring activity of disease to assess response to therapy in Graves’ patients
    • Less commonly, TSH receptor binding antibodies:
      • Can block the TSH receptor and produce hypothyroidism
  • In the setting of normal serum thyroid function:
    • Thyroid antibodies should generally not be measured except in special circumstances:
      • Such as a history of hyperthyroidism during pregnancy or recurrent miscarriages:
        • In these situations, both the stimulating and inhibiting TSHR Abs can cross the placenta to affect fetal thyroid function and potentially induce fetal goiter
      • Although serum thyroid antibody positivity during pregnancy:
        • Is associated with a higher risk of postpartum subacute thyroiditis:
          • Antibody screening in pregnant women is not currently recommended

Thyroid Physiology in Nonthyroidal Illness (Euthyroid Sick Syndrome)

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • The evaluation of a chronically ill or hospitalized patient with abnormal serum thyroid function tests:
    • Can often be challenging
  • Nonthyroidal illness is not considered a primary thyroid disorder:
    • Its pathophysiology is not completely understood:
      • Although it is known that the elevation of cytokines and hypoxia plays a significant role
    • It is generally recommended to avoid measuring serum thyroid function tests during acute illness:
      • Unless thyroid dysfunction is thought to be a significant contributor to the illness
  • Severe nonthyroidal illness:
    • Is accompanied by significant alterations in thyroid physiology
  • Due to the decreased availability in all of the thyroid binding proteins (thyroxine bindings globulin, transthyretin, albumin):
    • Serum total T4 and total T3 levels are reduced:
      • Whereas free levels are usually normal or slightly low (Figure)
    • Total T3 levels are further decreased:
      • Due to reduced Dio1 activity:
        • Which converts T4 to T3
    • A relatively greater amount of T4 is metabolized to the inactive metabolite:
      • Reverse T3 (rT3):
        • By Dio3
      • Although measurement of rT3 does not reliably distinguish nonthyroidal illness from primary hypothyroidism
      • The degree of serum rT3 elevation, depressed T3 / rT3 ratio, and decreased FT3 and FT4 concentrations:
        • Have been associated with higher mortality among patients in the intensive care unit (ICU):
          • Treatment with T4 or T3, however, does not consistently improve outcome
      • Whether other T4 metabolites, including 3,3′-diiodothyronine (3,3′-T2); 3,5-diiodothyronine (3,5-T2); and 3-iodothyronamine (3-T1AM):
        • Have functional roles in nonthyroidal illness remains unclear
Alternations in Serum Thyroid Hormone Concentrations During Acute Nonthyroidal Illness and Recovery.
The degree of change in hormone concentrations relates to the severity and duration of the illness. Thyroid-stimulating hormone (TSH) may also be suppressed during severe illness and transiently rise moderately above the reference range before returning to normal with recovery. Mortality correlates inversely with the degree of reduction in total T4 concentration. (From Farwell AF. Sick euthyroid syndrome in the intensive care unit. In: Irwin RS, Rippe JM, eds. Intensive Care Medicine. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2003.)
  • It is important that the diagnosis of primary thyroid dysfunction:
    • Is not established during severe illness based solely on an abnormal serum TSH
  • In nonthyroidal illness:
    • Serum TSH concentrations may be low, normal, or high:
      • Due to the TSH-lowering effects of commonly used medications (glucocorticoids, ipodate, amiodarone, dopamine) in patients managed for a nonthyroidal illness or from a reversible form of acquired central hypothyroidism in severe nonthyroidal illness
  • During the recovery phase of nonthyroidal illness:
    • The TSH may briefly rise above the upper reference range, as suppression of TSH lessens, before it normalizes
    • When possible, thyroid evaluation after recovery from an acute illness is recommended in patients suspected of having intrinsic thyroid disease

Most Ductal Carcinoma In Situ (DCIS) Presents as Mammographic Calcifications

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Fine linear or branching calcifications:
    • In a group or segmental distribution:
      • Are often associated with high-grade DCIS
  • Amorphous calcifications:
    • Are often associated with low-grade DCIS
  • Mammography relies on the presence of calcifications for the detection of DCIS:
    • Thus, lesions without calcifications are generally occult on mammography
  • Extensive DCIS:
    • Can present as a palpable mass
  • Nipple discharge:
    • Can also be a sign of either DCIS or invasive breast cancer
  • Paget disease:
    • Is a rare presentation:
      • Occurring in only 1% to 4% of women with breast cancer
    • It is characterized histologically by:
      • Intraepithelial tumor cells
      • It presents as a chronic ulceration or eczema of the nipple:
        • That can involve the surrounding areolar skin
    • It may be associated with invasion but, in the absence of invasion:
      • Is treated as DCIS
Morphology
The form of the calcifications is the most important factor in the differentiation between benign and malignant.
If calcifications cannot be readily identified as typically benign or as ‘high probability of malignancy’, they are termed of ‘intermediate concern or suspicious’.
If a specific etiology cannot be given, a description of the calcifications should include their morphology and distribution using the descriptions given in the BI-RADS atlas.
Distribution
In the BI-RADS atlas the following descriptions are given for the distribution of calcifications:
Diffuse or Scattered: diffuse calcifications may be scattered calcifications or multiple similar appearing clusters of calcifications throughout the whole breast.
Regional: scattered in a larger volume (> 2 cc) of breast tissue and not in the expected ductal distribution.
Clustered : at least 5 calcifications occupy a small volume of tissue.
Linear: calcifications arrayed in a line, which suggests deposits in a duct.
Segmental: calcium deposits in ducts and branches of a segment or lobe.
Diffuse or scattered distribution is typically seen in benign entities.
Even when clusters of calcifications are scattered throughout the breast, this favors a benign entity.
Regional distribution according to the BI-RADS atlas would favor a non-ductal distribution (i.e. benignity)

Segmental distribution would favor a ductal distribution (i.e. malignancy).
Sometimes this differentiation can be made, but in many cases the differentiation between ‘regional’ and ‘segmental’ is problematic, because it is not clear on a mammogram or MRI where the bounderies of a segment (or a lobe) exactly are.

Clustered calcifications are both seen in benign and malignant disease and are of intermediate concern.
When clusters are scattered througout the breast, this favors a benign entity.
A single cluster of calcification favors a malignant entity.
Linear distribution is typically seen when DCIS fills the entire duct and its branches with calcifications

#Arrangoiz #CancerSurgeon #BreastSurgeon #SurgicalOncologist #BreastCancer #LCIS #DCIS #DuctalCarcinomaInsitu #LobularNeoplasia #LobularCarcinomaInsitu #Surgeon #Teacher #Miami #Mexico #MSMC #MountSinaiMedicalCenter

Ductal Carcinoma In Situ (DCIS) and Axillary Staging

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Pure ductal carcinoma in situ (DCIS):
    • Is by definition non-invasive:
      • Thus lacks the ability to metastasize to axillary nodes and distant sites:
      • For this reason, surgical axillary staging is not recommended in the management of most patients with DCIS undergoing breast conserving surgery
  • Approximately 20% of patients with DCIS on core needle biopsy:
    • Will upstage to invasive cancer:
      • And may ultimately require surgical axillary staging
  • Factors associated with upstaging to invasive disease include:
    • A palpable mass at the time of diagnosis
    • Intermediate- or high-grade lesions
    • Comedonecrosis
    • ER negative (-) subtype
    • A large span of disease:
      • Typically cited as > 5cm
  • The location of the lesion (eg. upper outer quadrant):
    • Is not predictive of upgrade or spread to regional / distant sites
  • While some authors cite multifocality as a risk factor for upstaging:
    • It is more predictive of recurrence than upstage
  • One exception to the recommendation of omission of SLNB is:
    • For DCIS patients undergoing mastectomy:
      • First, most patients undergoing mastectomy for DCIS have a larger burden of disease:
        • Therefore have a higher likelihood of upstaging to invasive cancer:
          • For which surgical axillary staging is warranted
      • Second, while axillary mapping and sentinel lymphadenectomy may be feasible after mastectomy (with injection of radiocolloid and / or blue dye into the remaining skin):
        • The accuracy of this strategy has not been fully evaluated and is therefore not the recommended approach
      • However, since the rate of nodal positivity is low in these patients, newer strategies (such as injection of superparamagnetic iron oxide nanoparticles at time of mastectomy as a tracer for delayed sentinel lymph node dissection):
        • Are under investigation and may serve to decrease the number of patients with DCIS undergoing surgical axillary staging
  • References:
  • Due to the non-invasive nature of ductal carcinoma in situ (DCIS):
    • Assessment of the axilla is not indicated regardless of receptor status or grade with pure DCIS in the setting of breast conserving surgery
  • It may be considered if the patient is undergoing a mastectomy or the tumor is located in a position where excision may compromise future performance of a sentinel lymph node biopsy
  • Microinvasive DCIS:
    • Comprises 5% to 10% of all cases of DCIS
    • In a review of the literature, the reported incidence of axillary metastases in microinvasive DCIS:
      • Has ranged from 0% to 28%
    • Axillary staging is appropriate and sentinel node biopsy should be performed in the setting of microinvasive DCIS
  • References

Ductal Carcinoma In Situ with Microinvasive Disease

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • The eighth edition of the American Joint Committee on Cancer (AJCC) staging system:
    • Defines microinvasion as invasion of breast cancer cells through the basement membrane:
      • At one or more foci:
        • None of which exceeds a dimension of 1 mm
  • DCIS:
    • Is a Tis lesion:
      • It is classified as stage 0 cancer
  • DCIS with microinvasion:
    • Is considered T1mi:
      • It upstages DCIS from stage 0 to stage I disease
  • By definition, DCIS without microinvasion:
    • Does not have the ability to metastasize to axillary lymph nodes or distant sites:
      • Whereas DCIS with microinvasion does
  • Axillary metastases:
    • Have been reported in 0% to 20% of patients:
      • With DCIS with microinvasion
  • The incidence of microinvasion in DCIS:
    • Varies according to the size and extent of the index lesion
  • Lagios et al. reported:
    • A 2% incidence of microinvasion in patients with DCIS measuring less than 25 mm in diameter:
      • Compared with a 29% incidence of microinvasion in those with lesions larger than 26 mm
  • The incidence of microinvasion is also higher:
    • In patients with high-grade or comedo-type DCIS with necrosis
    • In patients with DCIS who present with a palpable mass or nipple discharge
  • There is conflicting data in the literature on the prognosis of DCIS with microinvasion compared to DCIS without microinvasion:
    • Historically, studies have shown that patients with DCIS with microinvasion have a worse prognosis compared with those who have DCIS alone
    • In a retrospective study of 1,248 serially sectioned DCIS tumors, de Mascarel et al:
      • Reported a 10.1% incidence of axillary metastases in cases of DCIS with microinvasion
      • Patients with DCIS alone had a better 10-year distant metastasis-free survival rate than patients with DCIS with microinvasion:
        • 98% and 91%, respectively
      • The overall survival rate was also better in patients with DCIS alone:
        • 96.5% vs. 88.4%
      • However, the metastasis-free and overall survival rates were worse:
        • In patients with invasive ductal carcinoma compared with those with DCIS with microinvasion
    • In a retrospective review of the SEER database from Champion et al., 134,569 women with DCIS alone, DCIS with microinvasion, and T1a intraductal carcinoma were compared:
      • They found that the disease-specific survival of DCIS with microinvasion was significantly different from the other two groups (DCIS alone: hazard ratio [HR] 0.59, confidence interval [CI] 0.43–0.80; invasive: HR 1.43, CI 1.04–1.96) but the overall survival of DCIS with microinvasion was similar to early invasive disease
      • Patients with DCIS alone had an improved overall survival compared to DCIS with microinvasion (HR 0.83, CI 0.75–0.93)
      • These results suggest that DCIS with microinvasion should be characterized as an early invasive tumor with a good outcome and that the therapeutic approach for these patients should be similar to that for patients with invasive cancer
    • However, some studies have pointed toward DCIS with microinvasion as having a more similar natural history to DCIS alone than to early-stage invasive disease:
      • In a review of 393 patients treated at Yale between 1973 and 2004, there was no significant difference between patients with DCIS alone and those with DCIS with microinvasion with regard to the presence of axillary metastases (in those who had axillary staging) or the likelihood of recurrence (locoregional and distant) or overall survival
    • In a more recent study from Zheng et al., 308 cases of DCIS alone were compared to 92 cases of DCIS with microinvasion and 111 cases of T1a tumors:
      • With a 25-month median follow-up, their analysis demonstrated no difference in disease-free survival and overall survival among the three groups

Nipple-Sparing Mastectomy

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Nipple-sparing mastectomy:
    • Has been a highly debated topic since first described by Hinton et al in 1984
  • There is consensus regarding some contraindications to nipple-sparing mastectomies, such as:
    • Direct involvement of the nipple or areola by tumor
  • However, many relative contraindications, such as:
    • Tumor size greater than 2 cm
    • Tumor location within 1 cm to 2 cm of the nipple-areolar complex:
      • Are still debated
  • Additional relative contraindication considerations are:
    • Perioperative smoking (or smoking within 4 weeks of surgery):
      • Which increases the risk of complication significantly:
        • As much as 2 to 10 times the risk, depending on the study
    • Obesity (BMI of ≥30):
      • Which doubles the risk
    • Older women:
      • Have not shown to have higher rates of nipple or skin necrosis in a large single institutional study
  • Despite early concerns:
    • There is no decreased survival by maintaining the nipple-areolar complex with mastectomy procedures, including in pathologic mutation carriers
  • Nipple-sparing mastectomies:
    • Are almost always performed in conjunction with some form of immediate reconstruction
  • The type of planned reconstruction influences the incision choice and outcomes:
    • Salibian et al. looked at immediate microvascular autologous reconstructions:
      • He found that vertical incisions had only a 5.8% rate of ischemic complications:
        • Whereas inframammary incisions had a 25% rate and lateral radial a 7.8% rate of ischemic complications
    • This has been shown in systematic reviews as well
  • References:
    • Galimberti V, Vicini E, Corso G, et al. Nipple-sparing and skin-sparing mastectomy: review of aims, oncological safety and contraindications. Breast. 2017;34 Suppl 1(Suppl 1):S82-S84. doi: 10.1016/j.breast.2017.06.034
    • McCarthy CM, Mehrara BJ, Riedel E, et al. Predicting complications following expander/implant breast reconstruction: an outcomes analysis based on preoperative clinical risk. Plast Reconstr Surg. 2008;121(6):1886-1892. doi: 10.1097/PRS.0b013e31817151c4
    • Parmeshwar N, Dugan CL, Barnes LL, et al. Nipple-sparing mastectomies in patients over the age of 60 years: factors associated with surgical outcomes. Ann Surg Oncol. 2023;30(13):8428-8435. doi: 10.1245/s10434-023-14278-6
    • Metere A, Fabiani E, Lonardo MT, Giannotti D, Pace D, Giacomelli L. Nipple-sparing mastectomy long-term outcomes: early and late complications. Medicina (Kaunas). 2020;56(4):166. doi: 10.3390/medicina56040166
      Salibian AA, Bekisz JM, Frey JD, et al. Comparing incision choices in immediate microvascular breast reconstruction after nipple-sparing mastectomy: unique considerations to optimize outcomes. Plast Reconstr Surg. 2021;148(6):1173-1185. doi: 10.1097/PRS.0000000000008282
    • Chicco M, Ahmadi AR, Cheng H-T. Systematic review and meta-analysis of complications following mastectomy and prosthetic reconstruction in patients with and without prior breast augmentation. Aesthet Surg J. 2021;41(7):NP763-NP770. doi: 10.1093/asj/sjab028
Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • The adult transgender population in the US:
    • Is estimated to be 0.6% of the population:
      • At least 1.4 million people
  • Cross sex hormonal therapy:
    • Is estrogen based for people transitioning male to female:
      • This results in stimulation of breast glandular tissue:
        • The breast tissue will develop with muted Tanner stage development:
          • Subareolar breast buds typically develop at 3 to 6 months of treatment and maximum development is achieved after 2 to 3 years of treatment
    • The addition of progesterone:
      • Has not been shown to increase breast size or add to feminization:
        • Thus, the risk of adding progesterone appears to outweigh the benefits
  • Breast enhancement / augmentation is a safe procedure:
    • Providers should educate their patients about the associated risk of various implant illnesses, including large cell lymphoma
  • Guidelines regarding imaging for transgender women:
    • May follow established guidelines for cis gendered males, the number of years of estrogen therapy, breast development, and known risk factors
  • The American College of Radiology guidelines:
    • Support digital breast  tomosynthesis or routine mammography for:
      • Transgender women 40 years old or more with more than 5 years of hormone use
    • For transgender women older than 25 to 30 years of age with more than 5 years of current or prior hormone therapy use or for individuals with genetic predisposition to breast cancer:
      • ACR also supports digital breast tomosynthesis or routine mammography as appropriate
    • In transgender women deemed at average risk with no hormone use or less than 5 years of use:
      • Routine breast screening imaging is not appropriate or necessary:
        • There is no longitudinal data, however
  • The risk of breast cancer for transgender women:
    • Does not appear to be significantly greater than that of natal males
  • Cross sex hormone therapy:
    • Does not appear to alter breast cancer risk
  • References:
    • Hayward J. Updates in Transgender Breast Imaging. Seminars in Ultrasound CT and MRI. Published online November 2022. doi:https://doi.org/10.1053/j.sult.2022.10.002
    • Guerrero DL, Sowinski J, Patel KM. (Apr 26, 2022). Effects of Gender-affirming Medical and Surgical Therapy on Breast Imaging Findings and Breast Cancer Risk. Appl Radiol. 2022; 51(3):24-32.
    • Legato MJ. PLASTICITY of SEX : The Molecular Biology and Clinical Features of Genomic Sex, Gender … Identity and Sexual Behavior.;  pages 187-205; 2020.
    • Lockhart, Ryan, and Aya Kamaya. “Patient-Friendly Summary of the ACR Appropriateness Criteria: Transgender Breast Cancer Screening.” Journal of the American College of Radiology , Jan. 2022, doi:https://doi.org/10.1016/j.jacr.2021.10.015.
    • Pivo S, Montes J, Schwartz S, et al. Breast Cancer Risk Assessment and Screening in Transgender Patients. Clinical Breast Cancer. 2017;17(5):e225-e227. doi:https://doi.org/10.1016/j.clbc.2016.08.003
    • Brown A, Lourenco AP, Niell BL, et al. ACR Appropriateness Criteria® Transgender Breast Cancer Screening. Journal of the American College of Radiology. 2021;18(11):S502-S515. doi:https://doi.org/10.1016/j.jacr.2021.09.005
    • Meggetto O, Peirson L, Yakubu M, et al. Breast cancer risk and breast screening for trans people: an integration of 3 systematic reviews. CMAJ Open. 2019;7(3):E598-E609. doi:https://doi.org/10.9778/cmajo.20180028
    • Hartley RL, Stone JP, Temple-Oberle C. Breast cancer in transgender patients: A systematic review. Part 1: Male to female. European Journal of Surgical Oncology: The Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2018;44(10):1455-1462. doi:https://doi.org/10.1016/j.ejso.2018.06.035
Rodrigo Arrangoiz, MD (Oncology Surgeon)

Thyroid Physiology During Pregnancy

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Significant changes in thyroid physiology occur during pregnancy:
    • This can make the interpretation of serum thyroid function tests challenging
  • During the first trimester of pregnancy:
    • Serum thyroxine binding globulin (TBG) concentrations increase by up to 50%:
      • As a result of altered estrogen induced glycosylation:
        • Which prolongs TBG half-life
    • The elevated TBG levels increase the quantities of protein-bound T4 and T3:
      • Which results in an increase in total serum T4 and T3 concentrations:
        • However, in euthyroid individuals:
          • The active or free levels of T4 and T3 remain normal
  • In addition, during the first trimester of pregnancy:
    • Levels of placental human chorionic gonadotropin (hCG) steadily increase:
      • Because hCG is a weak TSH receptor agonist:
        • This results in a small increase of free T4 (although still within the normal range) and a concomitant decrease in TSH:
          • Below the lower reference range in up to 15% of normal women in the first trimester
  • Serum TSH concentrations:
    • Should thus be assessed using trimester-specific ranges during pregnancy
  • The changes of reduced TSH and elevated FT4 are more pronounced:
    • In pregnancies associated with higher levels of hCG:
      • Such as multiple gestations and hyperemesis gravidarum, and are most extreme in hydatidiform moles
    • The physiologic suppression of TSH does not require medical intervention and usually normalizes after the first trimester of pregnancy

Indications for Partial Breast Irradiation in Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Tumor grade ≤ 2
  • Luminal-like subtypes
  • Small tumor (≤ 3 cm)
  • Negative lymphovascular space invasion
  • Low- to moderate-grade ductal carcinoma in situ (DCIS)
  • Age at diagnosis ≥ 50 years
  • Unicentric or unifocal disease
  • Clear surgical margins (> 5 mm)
  • Node negative (including isolated tumor cells)
  • No use of primary systemic therapy