The risk of underlying invasion in patients with DCIS:
Is roughly 25% (Bundred et al, BMJ. 2013) in this era of core biopsies
Risk of SLN metastasis in pure DCIS:
Is 0.2% to 0.7% (Zetterfund et al; BJS. 2014; Nicholson et al, EJSO. 2015):
Risk may rise to 9% if known micro-invasion (Meretoja et al, Ann Surg Onc. 2009)
Vacuum assisted devices (VAB):
Can lower the risk of invasion to 11% in retrospective data (Sumian et al, EJSO, 2016)
In prospective data (Cinnamome Study):
The upgrade was 39% (Tunon-De-Lara, Ann Surg Onco. 2015)
Routine MRI does not improve surgical outcomes:
Upgrade, size, or re-excision rates
(Fancellu et al, BJS. 2015; Chou et al ECON-AGRIN E4112, Radiology. 2021; Roque et al, NPJ breast cancer. 2022)
Dedicated breast PET? (Grana-Lopez et l Eur J Rad. 2020; Sasada et al, EJSO. 2021):
Up to know have not shown improve outcomes
There are approximately 50 retrospective studies evaluating nomograms and there predictive value on the risk of finding invasion in DCIS:
The usual risk factors are:
Size, grade 2 and 3, comedo necrosis, mass effect, micro-invasion:
Among “high-risk” DCIS:
Axillary evaluation in DCIS affects treatment but not survival (Coromilas et al, Ann Surg Onc 2016)
Axillary evaluation in DCIS increases complications and long-term morbidity (relative increase up to 6 to 8 times (Kilelea et al, Ann Surg Onc. 2018)
SLNB can be omitted in patients with DCIS planned for breast conserving surgery (BCS):
Detection rate at reoperation is 85.5% (GATA Study, Breast 2015)
NO data on feasibility after oncoplastic surgery
NO data on procedure accuracy
DCIS is noninvasive:
By definition, is unable to metastasize:
However, some studies have shown that up to 15% of patients with pure DCIS have isolated tumor cells (ITCs) or micrometastasis on nodal evaluation compared to others that show a 0.2% to 0.7% risk of nodal metastasis:
However, these small tumor deposits likely have little prognostic significance and may be cell clusters displaced by biopsy
In patients with DCIS detected by core biopsy:
There is a 15% to 25% associated risk of an invasive component when excised
Patients undergoing mastectomy for DCIS:
Should be offered SLNB since it would not be feasible to perform following mastectomy if invasive carcinoma is subsequently identified
ASCO consensus guidelines recommend that patients with DCIS who undergo breast-conserving operation should not routinely have SLNB:
However, SLNB could be discussed with patients undergoing breast conservation:
Who have a core biopsy diagnosis of DCIS and:
A large area of DCIS on imaging (2 to 5 cm)
High-grade DCIS
Comedonecrosis
When a physical examination or imaging shows a discrete mass
These findings have been associated with an increased risk of invasive cancer, and SLNB at the time of the initial operation could avoid a second operation
All of the guidelines that try and help us decide when to perform of SLNB in DCIS show a predictive value of a coin toss.
The oral cavity represents the entrance to the upper aerodigestive tract:
Which begins at the lips and ends at the anterior surface of the faucial arch
It is lined by:
Squamous epithelium with interspersed minor salivary glands
The oral cavity also contains the:
Dentoalveolar structures:
With the upper and lower dentition
The oral cavity is continuously exposed to inhaled and ingested carcinogens:
Thus it is the most common site for the origin of malignant epithelial neoplasms in the head and neck region
Known carcinogens for oral cavity carcinoma include:
Those present in tobacco, alcohol, and betel nuts
The association of human papilloma virus with oral cancer is not as well established as in oropharyngeal cancers
Primary tumors of the oral cavity may arise from the:
Surface epithelium
Minor salivary glands
Submucosal soft tissues
Lesions of dentoalveolar origin:
Representing a unique group of neoplasms and cysts
The various anatomic sites within the oral cavity as described by the American Joint Committee on Cancer (AJCC) and International Union Against Cancer (UICC) staging system are shown below:
Anatomic sites within the oral cavity.
More than 90% of malignant tumors in the oral cavity are:
Squamous cell carcinomas:
The remainder are:
Minor salivary gland carcinomas and other rare tumors
Most patients with cancer in the oral cavity are men:
Although the incidence of tongue cancer in women in the United States has progressively increased over the past several decades
In the Western world:
The tongue and floor of the mouth:
Are the most common sites of origin for primary squamous cell carcinomas in the oral cavity:
However, the retromolar trigone and buccal mucosa are the most frequently encountered primary sites in areas of the world where chewing of tobacco and / or betel nuts is common
The site distribution of various primary cancers in the oral cavity in the United States is shown bowls:
The site distribution of primary cancers in the oral cavity (MSKCC data 1985 to 2015; all patients re-staged according to AJCC 8th edition criteria).
Studies continue to evaluate for a subset of patients with DCIS who may not require adjuvant radiation therapy following breast-conserving surgery
In a prospective nonrandomized trial, ECOG E5194 evaluated two cohorts of patients:
Groups:
Group 1 had ≤ 2.5-cm low- and intermediate- grade DCIS
Group 2 had ≤ 1 cm high-grade DCIS
Both cohorts had margins of at least 3 mm and did not receive adjuvant radiation therapy
Tamoxifen was given to 30% of patients
Local recurrence at 5 years was:
6.1% in group 1 and 15.3% in group 2
The rate at 12 years was:
14.4% in group 1 and 24.6% in group 2
There was no plateau in the incidence of local recurrence over time
The Radiation Therapy Oncology Group (RTOG) 9804 study:
Randomized patients with < 2.5 cm low- and intermediate-grade DCIS and margins ≥ 3 mm to adjuvant radiation or no radiation therapy following partial mastectomy
Seven-year outcomes demonstrated an increase in local recurrence with the omission of radiation therapy (6.7% vs. 0.9%)
Tamoxifen was given to 62% of patients
Similar outcomes were also noted in the Dana Farber Cancer Institute prospective trial of excision alone
Trials are currently underway evaluating the omission of surgery for low-risk DCIS including:
The COMET (grade 1/2 ADH/DCIS ER+, primary outcome: ipsilateral invasive cancer at 2 years) – data recently published
The LORD (age > 45, primary outcome: ipsilateral invasive breast cancer free rate at 10 years)
LORIS trials:
However, there is limited prospective data published with respect to outcomes for patients forgoing surgery.
References:
McCormick B, Winter K, Hudis C, et al. RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation. J Clin Oncol. 2015;33(7):709-715.
Solin LJ, Gray R, Hughes LL, et al. Surgical excision without radiation for ductal carcinoma in situ of the breast: 12-year results from the ECOG-ACRIN E5194 study. J Clin Oncol. 2015;33(33):3938-3944.
Wong JS, Kaelin CM, Troyan SL, et al. Prospective study of wide excision alone for ductal carcinoma in situ of the breast. J Clin Oncol. 2006;24(7):1031-1036.
Oral leukoplakia (OL) is a white patch or plaque that cannot be rubbed off, cannot be characterized clinically or histologically as any other condition, and is not associated with any physical or chemical causative agent except tobacco:
Therefore, a process of exclusion establishes the diagnosis of the disease
In general, the term leukoplakia implies only the clinical feature of a persistent, adherent white plaque or patch; therefore, reserve the term for idiopathic lesions when investigations fail to reveal any cause:
The term carries absolutely no histologic connotation, although, inevitably, some form of disturbance of the surface epithelium is characteristic
Follow-up studies suggest that cancer is more likely to occur in individuals with idiopathic leukoplakia than in individuals who do not have this condition:
Thus, idiopathic leukoplakia is considered a premalignant lesion
Pathophysiology:
The etiology of most cases of OL is unknown (idiopathic)
In other cases, the initiation of the condition may depend on extrinsic local factors and / or intrinsic predisposing factors:
Factors most frequently blamed for the development of idiopathic leukoplakia include:
Tobacco use, alcohol consumption, chronic irritation, candidiasis, vitamin deficiency,endocrine disturbances, and possibly a virus
Epidemiology:OL occurs in fewer than 1% of individuals
OL is considered to be potentially malignant:With a transformation rate in various studies and locations:That range from 0.6% to 20%
A long-term follow-up study by Fan et al:Indicated that oral leukoplakia can increase the risk of esophageal squamous cell carcinoma
OL is more common in men than in women:With a male-to-female ratio of 2:1
Most cases of OL occur in persons in their fifth to seventh decade of life:Approximately 80% of patients are older than 40 years
Clinical presentation:
Oral leukoplakia (OL) manifests as patches or plaques that are bright white and sharply defined:
The surfaces of the patches are slightly raised above the surrounding mucosa
Individuals with OL are not symptomatic
The following three stages of OL have been described:
The earliest lesion is nonpalpable, faintly translucent, and has white discoloration
Next, localized or diffuse, slightly elevated plaques with an irregular outline develop:
These lesions are opaque white and may have a fine, granular texture
In some instances, the lesions progress to thickened, white lesions, showing induration, fissuring, and ulcer formation
Clinically, OL falls into one of the following two main groups:
The most common are uniformly white plaques (homogenous OL) prevalent in the buccal mucosa, which usually have low premalignant potential
Far more serious is speckled or verrucous leukoplakia:
Which has a stronger malignant potential than homogenous leukoplakia:
Speckled leukoplakia consists of white flecks or fine nodules on an atrophic erythematous base
These lesions can be regarded as a combination of or a transitionbetween leukoplakia and erythroplasia:
Which is flat or depressed below the level of the surrounding mucosal red patch, is uncommon in the mouth, and carries the highest risk of malignant transformation
The breast extends from the lateral border of the sternum to the midaxillary line:
In some individuals, into the axilla itself
The adult breast consists of:
Glandular and adipose tissue:
Together with a system of connecting ligaments
1. Nipple:
This is located at the apex of the breast and projects up to 1 cm
Optimizing its positioning is of utmost importance in breast surgery
In the average adult female the nipples lie in the midclavicular line:
19 cm to 21 cm from the sternal notch and 9 cm to 11 cm from the midline:
But their position varies widely according to shape, size and age
2. Areola:
This is a circular area of skin that surrounds the nipple
Its color darkens during pregnancy due to the deposition of melanin
The areolar skin contains Montgomery glands:
Which secrete a protective oily lubricant
3. Glandular tissue:
The glandular tissue is the functional component of the lactating breast and the site of milk production, which is passed to the nipple via a system of ducts:
Each breast, or mammary gland:
Contains 15 to 20 lobes and each lobe is comprised of 20 to 40 terminal ductal lobular units (TDLU):
The TDLU is the functional unit of the breast
The breast mound is roughly hemispherical
The bulk of the glandular tissue is found in the upper outer quadrant:
Which is the commonest site of malignancy.
4. Adipose tissue:
This forms up to 70% of the breast mass:
It is the main determinant of breast size
5. Ligaments:
The structure and shape of the breast is maintained by fascial and ligamentous supports:
As first described by Sir Astley Cooper in 1840
Superficial fascial system:
The breast is enveloped by the superficial and deep laminae of the superficial fascia:
The superficial lamina is separated from the dermis by a thin layer of fatty tissue:
But is often difficult to identify as a separate entity
Suspensory ligaments of Cooper:
These fibrous strands extend through the breast parenchyma between the layers of the superficial and deep (pre-pectoral) fascia:
They help to maintain a non-ptotic breast shape
6. Axillary tail (of Spence):
There is a variable extension along the inferior edge of pectoralis major towards the axilla
This usually lies within the subcutaneous fat but may penetrate the axillary fascia to lie adjacent to the lymph nodes
Occasionally it is a separate entity with ducts that do not drain to the nipple.
7. Retromammary space:
In reality this is not a space but a plane of loose connective tissue lying between the deep lamina of the superficial fascia and the deep pre-pectoral fascia
Chassaignac bursa (also known as the retromammary bursa, submammary serous bursa or occasionally Chassaignac bag):
Is the space behind the breast, lying between the pectoralis fascia posteriorly and deep layer of superficial fascia anteriorly
This is the plane of dissection in which a subglandular pocket can be created for insertion of a prosthesis for breast augmentation
8. Muscle:
The medial two-thirds of the base of the breast lie over the pectoralis major muscle
The lateral one-third lies over serratus anterior and a small portion of the rectus abdominis and external oblique muscles
The muscles are separated from the breast by the deep fascia
9. Rib cage:
Deformities of the ribs, including those that are secondary to a spinal deformity can lead to an apparent asymmetry of breast position and/or shape
Vascular Supply of the breast:
The breast has a rich blood supply:
Which permits safe division and excision of breast tissue:
The viability of the nipple areolar complex is dependent on vessels that pass through the gland:
Which must therefore be preserved
There are three main arterial systems:
Internal Thoracic (Mammary) Artery:
Is responsible for roughly 60% of the vascular supply to the breast
Arising directly from the subclavian artery, the internal thoracic artery passes posterior to the subclavian vein and runs along the edge of the sternum, deep to the costal cartilages
Perforating branches of the internal thoracic artery pass through the 2nd to 6th intercostal spaces to supply the medial half of the breast:
The 2nd and 3rd perforators are the predominant vessels and these are preferred for anastomosis when reconstructing the breast with a free tissue transfer
Lateral Thoracic Artery:
A branch of the second portion of the axillary artery:
Supplies the upper outer quadrant of the breast
The lateral thoracic artery runs along the lower border of the pectoralis minor muscle and curls around the lateral border of pectoralis major to enter the breast
Other branches of the lateral thoracic artery perforate pectoralis major to supply the overlying breast tissue
Posterior Intercostal Arteries:
The lateral branch of the posterior intercostal arteries divides into posterior and anterior branches
The anterior branches from the 3rd to 6th intercostal spaces supply the lateral portion of the breast and the overlying skin through their mammary branches
Other Supply:
The axillary artery also provides other branches to the breast, including the:
Superior thoracic artery:
A branch from the first part of the axillary artery)
The pectoral branch of the thoracoacromial artery and the subscapular artery
The venous drainage of the breast is via two venous systems:
Superficial system:
Which lies within the subdermal venous plexus:
The pattern of drainage is highly variable
Deep system:
The deep venous system parallels the arterial supply:
The medial half of the breast drains via veins that accompany the perforating branches of the internal mammary artery through the intercostal spaces, back to the internal mammary vein
The lateral thoracic veins drain into the axillary vein
The posterior intercostal veins drain into the azygous vein on the right and the hemiazygous vein on the left
Innervation of the breast:
The nerve supply to the breast consists of sensory fibres from the skin and sympathetic efferent fibres to the blood vessels, glandular tissue and smooth muscle cells in the skin and nipple
The sensory nerve supply is derived from cutaneous branches of the intercostal nerves:
Medially:
Anterior branches of the 1st to 6th intercostal nerves
Laterally:
Lateral branches of the 2nd to 6th intercostal nerves
Nipple areola complex:
Supplied by the anterior branch of the 4th intercostal nerve
There is an extensive nerve plexus within the nipple
The skin of the nipple areola complex contains free nerve endings, Meissner’s corpuscles and Merkel disc endings
Partial mastectomy only or partial mastectomy followed by lattice radiotherapy (LRT; a novel technique of delivering heterogeneous doses of radiation to voluminous tumors not amenable to surgery) for the treatment of localized DCIS
The trial showed a clear benefit for the addition of radiation
Patients enrolled in the NSABP B-24 trial:
Were randomly assigned to receive LRT or LRT plus tamoxifen (LRTT)
At 15-year follow-up:
The risk of death in these trials was low:
Ranging from 2.3% for patients who had LRTT to 4.7% for patients who had LRT
Ipsilateral breast tumor recurrence was:
35% (19.6% invasive, 15.4% DCIS) in the lumpectomy only arm of B-17 and 19.8% (10.7% invasive, 9.0% DCIS) in the LRT arm
In B-24 IBRT was 16.6% (9.0 invasive, 7.6% DCIS) in the LRT arm and 13.2% (6.6% invasive, 6.7% DCIS) in the LRTT arm
The risk of contralateral new primary ranged from:
4.9% (3.3% invasive, 1.6% DCIS) in the LRTT arm of B-24 to 9.3% (5.6% invasive, 3.7% DCIS) in the LRT arm of B-17
References:
Wapnir IL, Dignam JJ, Fisher B, Mamounas EP, Anderson SJ, Julian TB, et al. Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst. 2011;103(6):478-488.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 