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.
Significant increase in incidence after mammography screening:
10-fold to 17-fold increase from 1970’s to 2004:
1 in 1300 mammograms
Represents 20% to 25% of all screen-detected breast neoplasias diagnosed annually
Based on autopsy data:
The prevalence of undetected DCIS may exceed 20% in women over 40:
Underscoring the concern for overdiagnosis:
Modeling studies estimate up to 65% of DCIS may be overdiagnosed
DCIS by it self:
Is not a risk to life
DCIS may progress to invasion and compromise survival:
If left untreated:
1 in 6 DCIS patients:
Progress to invasive breast cancer (IBC):
70% estimated to remain indolent
At this time we do not have any robust biomarkers:
That can quantify the risk of progression to IBC or
Help us separate indolent disease:
From the potentially dangerous lesions
Risk of overtreament:
The increase incidence of DCIS in mammographically detected cases:
Has not lead to a decrease in the incidence of IBC or reduction of IBC morality
Risk factors for progression / recurrence of DCIS:
The risk factors for IBC recurrence may be different from the risks factors for DCIS recurrence?
Risk of IBC recurrence:
African American race
Premenopausal status
Detection by palpation
Involved margins
High histologic grade
High p16 expression
Risk of IBC or DCIS recurrence:
DCIS size
Histology type
Comedo necrosis
Grade (High)
Young age
Close margins or positive margins
Patients with DCIS that recur with an IBC:
Some patients with DCIS may develop:
Progression of there disease:
30% (1 out of 6)
Some will have a de novo invasive breast cancer
Some might have a missed invasive cancer?
Patient that have a DCIS recurrence:
Might be a true in situ recurrence
De novo DCIS
Residual disease?
Studies are describing observations of events like:
Synchronous IBC
Subsequent ipsilateral or contralateral DCIS or IBC (often a mixture)
We have limited data on DCIS progression with paired molecular profiles
The most consistent biological feature of DCIS:
Heterogeneity:
In clinical presentation
Morphology
Protein expression:
Including receptor status
Gene expression
Genetic alterations
Epigenetic alterations
The heterogeneity is:
Between patients – within the lesion – and within cells in a single duct
Morphological features that help us predict progression are:
Histologic grading:
Combing the nuclear grade 1 to 3 and necrosis into a three tier system (the good, the bad, and the ugly):
Low / intermediate / high grade
Grade 1 to 3
Van Nuys Group 1 to 3
DIN 1 to 3
We all know that there is regression towards the mean and substantial interobserver variation
DCIS is classified by two complementary systems:
Nuclear grade (the primary classification):
Low (grade I), intermediate (grade II), and high (grade III):
Based on nuclear size, pleomorphism, chromatin pattern, nucleoli, mitotic activity, and cell polarization
Nuclear grade is the most reproducible and clinically relevant parameter
Architectural pattern (secondary / noncore):
Solid, cribriform, micropapillary, papillary, and comedo:
Multiple patterns frequently coexist within a single lesion, limiting reproducibility
Morphologic Features Suggestive of Progression
Unclear prognostic value of the 3-tier system:
We suspect that:
Low to intermediate grade = low risk of progression
High grade system = high risk of progression or shorter time to progression
Maxwell, A.J. Eur.J.Surg.Oncol.,2018, Ryser, MD. J.Natl Cancer Inst., 2019:
Risk of ipsilateral recurrence (DCIS / IBC) at 10 years:
High grade 17.6% (95% CI=12.1-25.2%)
Non high grade 12.2 (95% CI=8.6-17.1%):
Including grade 2
There is overlap in the confidence intervals
Low grade DCIS are the lesions that might have:
Discontinuous growth (multifocal gaps up to 1 cm) and skip lesions that might lead to a:
Greater likelihood of residual disease and recurrence?
DCIS has heterogeneity of grade within the same lesion
Histologic subtype as a prognostic factor:
Subtype:
Cribriform:
Is more often a grade 1 lesion
Comedo type:
Is more often a grade 3 lesion
Usually histology subtype correlates with grade but:
There is often a mixture of growth patterns:
Compromising the use for prognostication
Can we use histology as a prognostic feature?
Tumor micro environment:
Could potentially be the most important morphologic feature suggestive of progression especially:
Circumferential periductal fibrosis and associated tumor infiltrating lymphocytes (TIL):
Indicating host reaction to the tumor cells
Tumor micro environment includes:
Myoepithelial cell layer
Tumor infiltrating lymphocytes (TIL)
Adipocytes
Fibroblasts
Matrix
The border around the myoepithelial layer might have prognostic value
The myoepithelial cell layer acts as a gatekeeper:
Has tumor suppressive functions
The largest gene expression change from normal tissue to DCIS:
Occurs in the myoepithelial cell layer
DCIS is associated myoepithelial cell loss:
That leads the decrease tumor suppressor functions
The myoepithelial cell layer is lost in IBC
Myoepithelial cell layer acts as a GATEKEEPER (Tumor Suppressive Functions)
Disruption of the myoepithelial defense:
IBC with DCISBrown color – myoepithelium Arrows point to the disrupted myoepithelial cell layer (micro-invasion)
Conflicting data on prognostic value of TIL:
Some studies have reported no prognostic value of stromal TIL for subsequent recurrences:
Does the spatial location of the immune cells matter?
The TIL in direct contact with the DCIS might be more important that the TIL that are further away
Other studies have shown a correlation between higher levels of TIL and increased risk of subsequent IBC and a shorter (ipsilateral) recurrence-free survival
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:
Is classified as stage 0 cancer
DCIS with microinvasion is considered:
T1mi:
Upstages DCIS from stage 0 to stage I disease:
The earliest stage of invasive cancer:
In the AJCC staging system
By definition:
DCIS does not have the ability to metastasize to axillary lymph nodes or distant sites:
Whereas DCIS with microinvasion does
Axillary metastasis:
Has been reported in 0% to 20% (0% to 28% in some series) 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. (1989):
Reported a 2% incidence of microinvasion in patients with DCIS:
Measuring ≤ 25 mm in diameter
Compared with a 29% incidence of microinvasion:
In those with lesions ≥ 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
Nipple discharge
Historically, patients with DCIS with microinvasion:
Have been observed to have a worse prognosis:
Compared with those who have DCIS alone
Mirza et al. (2000):
Reported the long-term results of breast-conserving therapy in patients with:
DCIS
DCIS with micro-invasion (T1mi)
T1 invasive breast cancers
The 20-year disease-specific survival rates in patients with:
DCIS were better:
Than those among patients with DCIS with microinvasion or with T1 invasive tumors
Patients with micro-invasion (T1mi) and those with T1 tumors:
Had similar survival rates
In a retrospective study of 1,248 serially sectioned DCIS tumors, de Mascarel et al. (2002):
Reported a 10.1% incidence of axillary metastases:
In cases of DCIS with microinvasion
Patients with DCIS 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 compared to DCIS with microinvasion:
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
These results suggest that DCIS with microinvasion:
Should be characterized as a small invasive tumor with a good outcome:
The therapeutic approach for these patients should be similar to that for patients with invasive cancer
However, more recent studies have pointed toward DCIS with microinvasion having a more similar natural history to pure DCIS than to early-stage invasive disease:
In a review of 393 patients treated at Yale between 1973 and 2004:
There was no statistically significant difference between patients with DCIS 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 (Parikh et al., 2012)
Avoids all the disadvantages of a lateral mandibulotomy and the sequelae of a midline mandibulotomy
A paramedian mandibulotomy offers significant advantages:
Wide exposure to the surgical field
Preservation of the geniohyoid and genioglossus muscles:
Leading to preservation of:
The hyomandibular complex
The only muscle requiring division is the mylohyoid muscle:
Which leads to minimal swallowing difficulties
A paramedian mandibulotomy does not cause denervation or devascularization of the skin of the chin or the teeth and mandible
Fixation at the mandibulotomy site is easy
The site of the mandibulotomy does not fall within the lateral portal of radiation therapy if the patient needs postoperative radiotherapy:
Thus at present a paramedian mandibulotomy remains an optimal surgical approach for access to posteriorly located larger lesions of the oral cavity and tumors of the oropharynx and parapharyngeal space
The 2025 ATA guidelines (Recommendation 11) formally endorse active surveillance (AS) as an acceptable management option for cT1aN0M0 papillary thyroid cancers (≤1 cm), graded as a conditional recommendation with low certainty evidence.
For recurrent / persistent nodal disease, the guidelines state that stable disease can continue monitoring, while bulky and / or invasive recurrent disease is generally best treated with surgery.
Recommendation 14 specifies that surgical resection is indicated when there is tumor growth ≥ 3 mm, new biopsy-proven lymph node metastases, distant metastases, extrathyroidal extension, or patient preference.
The NCCN Thyroid Carcinoma Guidelines (v1.2026) similarly note that AS is supported by low-quality evidence for papillary thyroid microcarcinoma ≤ 1 cm, with limited data for cancers >1 cm.
Quantitative Data on Progression During Active Surveillance
A 2026 systematic review and meta-analysis (10 studies, n = 841) provides the most comprehensive pooled data. The overall pooled progression rate during AS was 23% (95% CI, 12–34%), rising to 32% in biopsy-confirmed cases. Critically, after adjustment for follow-up loss, the estimated progression rate increased to 35% to 70%, suggesting that reported rates may substantially underestimate true progression. Subgroup analyses showed higher progression in patients with elevated baseline thyroglobulin (log-transformed Tg: 1.02 in progressors vs. −0.07 in stable, p < 0.05) and in those with advanced stage (≥ 5% Stage IV patients: 28% vs. 14%, p < 0.05).
Individual cohort studies provide additional granularity:
Jerkovich et al. (2022): 50 patients with cytology-confirmed metastatic lymph nodes (mean size 10.1 mm) under AS; 24% had lymph node growth at median 29 months. The only predictor of growth was a Tg rise ≥0.5 ng/mL (OR 16.2, p = 0.020). Median progression-free survival was 6.6 years. Among the 7 patients who underwent surgery after progression, none had structural incomplete response at follow-up.
Walter et al. (2023): 40 patients with metastatic cervical lymph nodes ≤2 cm; 35% progressed (17.5% enlargement ≥3 mm, 17.5% new metastasis) at median 27.5 months. Of 14 who progressed, 6 remained on AS with 5/6 showing no further progression.
Tufano et al. (2015): Lateral neck lymph nodes with suspicious ultrasonographic features demonstrated a low potential for structural progression—over a median of 3.5 years, only 9% increased by more than 5 mm.
Size Thresholds: Confirmed
The ATA-endorsed size thresholds for FNA biopsy consideration (and by extension, the boundary for observation) are ≥8 mm in the central compartment and ≥10 mm in the lateral compartment. The NCCN guidelines do not specify exact size cutoffs for AS of recurrent nodes but recommend “disease monitoring for non-progressive disease that is stable and distant from critical structures”.
Thyroglobulin Doubling Time as a Prognostic Marker
A Tg doubling time (Tg-DT) <1 year portends poor prognosis, while Tg-DT >2 years signifies good prognosis. The AHNS consensus statement recommends cross-sectional imaging at 4 to 6 month intervals when Tg-DT is <1 year, with longer intervals for longer doubling times.
A study by Albano et al. demonstrated that a TgDT threshold of ≤2.5 years predicted positive FDG-PET/CT results with 93% sensitivity and 87% specificity (AUC = 0.911), outperforming absolute Tg level alone. Ito et al. (2025) showed that combining unstimulated Tg ≥3 ng/mL with a Tg doubling rate ≥0.33/year identified the highest-risk group for both lymph node and distant recurrence.
FDG-PET Avidity: Strong Prognostic Data
FDG-PET avidity is a well-established marker of aggressive biology. Robbins et al. demonstrated that a positive FDG-PET/CT predicted a 7-fold increased risk of mortality compared with negative FDG findings. FDG uptake reflects tumor dedifferentiation and is a major negative predictive factor for response to RAI treatment. An SUVmax >5.0 has been associated with very high rates of disease progression even in the presence of mixed iodine-avid disease, and SUVmax >10 has been linked to shorter locoregional disease-free survival and anaplastic transformation. The 2025 ATA guidelines recommend FDG-PET/CT as both a diagnostic and prognostic tool in high-risk patients, particularly those with aggressive histologies or negative RAI imaging.
BRAF/TERT Mutations: Quantified Risk
The co-occurrence of BRAF V600E and TERT promoter mutations is the most powerful molecular predictor of aggressive behavior. A meta-analysis showed this combination was associated with reduced disease-specific survival (RR 15.09, 95% CI 7.75–29.37), far exceeding BRAF V600E alone (RR 5.34). Song et al. (2016) reported that co-existing BRAF + TERT mutations increased recurrence risk (HR 4.64 for BRAF/TERT; HR 5.36 for RAS/TERT) and mortality (HR 15.13 for BRAF/TERT; HR 14.75 for RAS/TERT). Ryu et al. (2026) demonstrated that TERT-mutant tumors show continuous recurrence over time without the expected decline seen in TERT-wildtype cases, and are associated with significantly higher mortality. Xing et al. (2025) showed that the BRAF/TERT genetic duet worsened survival across all AJCC stages.
Reoperative Surgery Outcomes
The 2025 ATA guidelines report that reoperative surgery results in 27% to 63% excellent responses, 5.7% to 13.3% biochemically incomplete responses, 10% to 44% structurally incomplete responses, and 8.6% to 30% indeterminate responses. Independent risk factors for incomplete response after reoperation include age >45 years, aggressive histology, and lymph node ratio >0.6 at initial resection.
The Central Tension: Is Progression Evidence That Surveillance Is Failing?
The assertion that “progression itself is evidence that surveillance is failing” requires nuance. The data suggest that not all progression is equal:
Slow, limited nodal growth in low-risk patients can often be managed with continued observation or delayed intervention without compromising outcomes. In the Jerkovich cohort, all 7 patients who underwent surgery after progression on AS achieved structural complete response. In the Walter cohort, 5 of 6 patients who remained on AS despite progression showed no further growth.
However, the 2026 meta-analysis raises a cautionary note: true progression rates may be 2–3 times higher than reported due to follow-up loss, and AS “should be considered with caution”. Trimboli and Piccardo (2026) argue that until stronger prospective data are available, AS in DTC should be applied within a well-defined multidisciplinary framework with transparent communication about uncertainties.
The evidence therefore supports a nuanced position: AS is appropriate and evidence-based for carefully selected patients with stable, low-volume recurrence, but documented progression—particularly when accompanied by rising Tg kinetics, FDG avidity, aggressive molecular profile, or threatened critical structures—should prompt serious consideration of intervention. The key is that AS is not a passive strategy but an active decision-making framework requiring serial reassessment.
👉A lateral mandibulotomy has several disadvantages:
First, the muscular pull on the two segments of the mandible is unequal:
Putting the mandibulotomy site under significant stress and causing a delay in healing:
For this reason, intermaxillary fixation may be required
Second, the ability to gain access to the suture line to maintain cleanliness following surgery in the oral cavity is hampered as a result of intermaxillary fixation:
Leading to poor oral hygiene and the potential risk for sepsis of the suture line
In addition, a lateral mandibulotomy poses several anatomic disadvantages:
Leading to denervation of the teeth distal to the mandibulotomy site and the skin of the chin:
As a result of transection of the inferior alveolar nerve
A lateral mandibulotomy also causes devascularization of the distal teeth and the distal segment of the mandible:
From its endosteal blood supply
The exposure provided by a lateral mandibulotomy is:
Limited
If the patient needs postoperative radiation therapy:
The mandibulotomy site is directly within the lateral portal of radiation therapy:
Leading to delayed healing and complications at the site of the mandibulotomy
👉For these reasons, a lateral mandibulotomy is not recommended
Are available for resection of primary tumors of the oral cavity
The choice of a particularapproach will depend on factors such as:
The size and site of the primary tumor:
Anterior versus posterior
As well as its depth of invasion
Proximity to the mandible or maxilla
Factorssuch as dentition, size of the oral aperture, trismus, and the size and mobility of the tongue:
Also influence selection of the surgical approach
The various surgical approaches such as:
Peroral, mandibulotomy, lower cheek flap approach, visor flap approach, and upper cheek flap approach are shown in Figure
The transoral approach has wider applications with technologic advances using:
Lasers (transoral laser microsurgery [TLM]) and robotics (transoral robotic surgery [TORS])
Various surgical approaches. A, Peroral. B, Mandibulotomy. C, Lower cheek flap. D, Visor flap. E, Upper cheek flap.
When the peroral approach does not offer adequate exposure:
The visor flap or cheek flap approaches (upper or lower) become necessary
The visor flap approach:
Provides sufficient exposure for anteriorly located lesions:
But is not satisfactory for tumors located in the posterior oral cavity
The benefit of this approach is that it avoids a lower lip–splitting incision:
But produces permanent numbness of the chin:
Because the mental nerves need to be transected for adequate mobilization of the flap
It also may cause sagging of the lower lip and drooling:
Because of a loss of support and sensation:
Thus its utility is limited
The lower cheek flap approach:
Requires a midline lip–splitting incision that is continued laterally into the neck for exposureand neck dissection:
This approach provides excellent exposure for nearly all tumors of the oral cavity:
Except those of the upper gum and hard palate
Mandible resection (marginal or segmental) and reconstruction:
Require the lower cheek flap approach in most instances
The lower cheek flap approach:
Is required for marginal or segmental mandibulectomy of tumors adjacent to the body of the mandible
The upper cheek flap approach (the Weber-Ferguson incision and its modifications):
Is required for resection of larger tumors of the hard palate and upper alveolus:
Particularly if they are posteriorly located
Access to larger tumors of the tongue, particularly those closer to the base of the tonguewhere the mandible is not involved:
Requires wider exposure for resection:
A mandibulotomy or mandibular osteotomy is an excellent mandible sparing surgical approach:
Designed to gain access to the oral cavity or oropharynx for resection of primary tumors otherwise not accessible through the open mouth or by the lower cheek flap approach (Figure)
A mandibulotomy is an excellent mandible-sparing surgical approach to gain access to bulky tumors of the oral cavity or oropharynx.
To determine the need and extent of mandible resection:
It is essential to understand the pathwayby which oral cancers invade the mandible
Primary carcinomas of the lip, buccal mucosa, tongue, and floor of the mouth:
Extend along the surface mucosa and the submucosal soft tissues:
To approach the attached labial, buccal, or lingual gingiva
From this point:
The tumor does not extend directly through intact periosteum and cortical bone toward the cancellous part of the mandible:
Because the periosteum acts as a significant protective barrier
Instead:
The tumor advances from the attached gingiva toward the alveolus:
In patients with teeth:
The tumor extends through the dental socket into the cancellous part of the bone and invades the mandible in that fashion (Figure)
Tumor invasion of the dentate mandible occurs through the dental socket to the cancellous bone and then to the alveolar canal
In edentulous patients:
The tumor extends up to the alveolar process and then infiltrates the dental pores in the alveolar ridge and extends to the cancellous part of the mandible (Figure)
Tumor invasion of the edentulous mandible occurs through the dental pores on the alveolar process to the cancellous bone and then to the alveolar canal.
Thus even in patients with early invasion of the mandible:
A marginal mandibulectomy is feasible because the cortical part of the mandible inferior to the roots of the teeth:
Remains uninvolved and can be safely spared
In edentulous patients, however, the feasibility of marginal mandibulectomy depends on the vertical height of the body of the mandible:
With aging, the alveolar process recedes and the mandibular canal comes closer to the surface of the alveolar process:
As shown in the Figure, the resorption of the alveolar process eventually leads to a “pipestem” mandible in elderly patients
Vertical height and location of the alveolar canal in dentate and edentulous mandibles.
The ability to perform a satisfactory marginal mandibulectomy in such patients is almost impossible:
Because the probability of iatrogenic fracture or postsurgical spontaneous fracture of the remaining portion of the mandible is very high:
Similarly, in patients who have received previous radiotherapy:
A marginal mandibulectomy should be performed with extreme caution:
The probability of pathological fracture at the site of the marginal mandibulectomy in such patients is very high
When the tumor extends to involve the cancellous part of the mandible:
A segmental mandibulectomy must be performed
A segmental mandibulectomy also may be required in patients with massive primary tumors with significant soft tissue disease in the proximity of the mandible
Rodrigo Arrangoiz MS, MD, FACS, FSSO is an Assistant Professor at New York Medical College School of Medicine Division of Surgical Oncology at Mount Sinai Medical Center
He is first author on some publications on oral cavity cancer:
Oral Tongue Cancer: Literature Review and Current Management
Rodrigo Arrangoiz MS, MD, FACS, FSSO 