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• Male breast cancer occurs in less than two per 100,000 men in the United States:
  • Accounts for less than 1% of all breast cancers
• Men are often diagnosed at a higher stage than women:
  • Approximately 40% of male patients:
    • Have more than three nodes involved with metastases at diagnosis
• Several small studies have examined the role of SLNB in male breast cancer:
  • They have shown its accuracy:
    • SLNB can spare a significant number of male patients;
      • The morbidity of ALND

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• DCIS is noninvasive:
  • By definition, is unable to metastasize:
    • However, studies have shown that up to 15% of patients with pure DCIS:
      • Have isolated tumor cells (ITCs) or micrometastasis on nodal evaluation
    • However, these small tumor deposits:
      • Likely have little prognostic significance:
        • They may represent only cell clusters displaced by biopsy
• In patients with DCIS detected by core biopsy:
  • There is a 15% to 20% 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 cm 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

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• The lymph node that is the most likely to harbor metastatic disease:
  • Is the sentinel lymph node
• In a landmark study published in 1994:
  • A vital blue dye:
    • Was used to identify the first node in the lymphatic chain to harbor metastatic tumor
  • An axillary dissection was then completed:
    • The pathologists evaluated the sentinel lymph node separately from the remaining axillary contents:
      • The sentinel node was identified with a specificity of 96% in 174 consecutive patients with various stages of breast cancer
• As the sentinel node technique was further explored:
  • Additional studies demonstrated that SLNB could be reliably preformed using:
    • Radiolabeled colloid
    • Vital blue dye:
      • Methylene blue
      • Isosulfan blue
      • Blue patent
    • Both techniques:
      • Radiolabeled colloid and vital blue dye
• The American Society of Clinical Oncology (ASCO):
  • 2014 Sentinel Lymph Node Biopsy Early-Stage Breast Cancer Update:
    • Evaluated the performance of SLNB and reported that:
      • False negative rates of the procedure ranged from:
        • 4.6% to 16.7%
      • An overall accuracy of:
        • 93% to 97.6%
    • Factors that increase the false negative rate of SLNB are:
      • Obesity
      • Tumor location
      • Failure to localize a lymph node on lymphoscintigraphy
      • Patient age
      • Surgeon experience
• When radiolabeled sulfur colloid is used:
  • 0.4 mCi to 2 mCi of technetium-99m (99mTc)-labeled particles:
    • Measuring 50 to 200 nm in diameter are injected into the breast:
      • From 30 minutes to 24 hours before SLNB
    • Higher doses:
      • Are often used if the patient is injected the day prior to the operation
  • After injection:
    • The area is massaged gently for approximately 5 minutes:
      • To improve the lymphatic drainage
  • Patients may undergo static scintigraphy images:
    • To aid localization
• In the operating room:
  • A gamma probe is used to identify the radioactive node
    • “Hot” nodes:
      • Nodes that qualify as sentinel lymph nodes are those that have:
        • Counts greater than 10% of the ex vivo counts of the most radioactive lymph node
• Using a threshold of more than 10% of the hottest node:
  • Has been validated and correctly identifies:
    • 98% of sentinel lymph nodes
• 99mTc-labeled sulfur colloid and lymphoscintigraphy:
  • Can identify alternate lymphatic drainage:
    • And are particularly useful in patients with previous axillary operations
• Most surgeons find the use of both radioisotope and blue dye to be more successful than one method alone:
  • However, either may be used alone in experienced hands
• If vital blue dye is used:
  • 3 ml to 5 mL of solution is injected:
    • Followed by at least 5 minutes of massage is used:
      • To improve lymphatic drainage
• With either technique:
  • A transverse incision is then made:
    • Along the inferior margin of the hair-bearing region of the axilla
  • Blunt and sharp dissection:
    • Is used to identify a lymphatic track or blue-stained or “hot” node
  • Following removal of the sentinel lymph node:
    • The surgeon should palpate the axilla for any additional suspicious nodes and remove these as well
  • Although most patients have one sentinel lymph node:
    • Multiple nodes may be identified and should be removed
  • Care should be taken to remove only the targeted lymph node or nodes:
    • Separating them carefully from investing axillary fat:
      • As excessive dissection and tissue removal:
        • May increase rates of postprocedure seroma or lymphedema remove these as well
• Complications following SLNB are less frequent than complications following ALND:
  • Especially with respect to:
    • Lymphedema, sensory loss, and mobility
• Patients following SLNB:
  • Report improved quality of life and a more rapid return to work:
    • However, the International Cooperative Group Trial:
      • Reported lymphedema and seroma in:
        • 7% of patients treated with SLNB
      • Wound infection and hematoma rates:
        • Were both 1%
      • Shoulder or arm pain and decreased abduction are:
        • Also occasionally seen with SLNB.
• Both methylene blue and 1% isosulfan blue dye:
  • Are commonly used to identify sentinel lymph nodes:
    • Isosulfan blue has a documented risk of allergic reaction, resulting in:
      • Rash, urticaria, and hypotension:
        • In as many as 3% of patients
      • Anaphylaxis:
        • In less than 1%
  • Although methylene blue is less costly and has a lower risk of anaphylaxis:
    • It is associated with skin necrosis in up to 10% of patients:
      • When injected intradermally or subcutaneously
    • For this reason, it should be diluted 1:2 in saline:
      • And an intradermal injection should be avoided
  • Multiple studies have tried to prove the superiority of one or other of these dyes:
    • They appear equivalent
• Debate remains about the location of injection:
  • Peritumoral, subareolar, subdermal, and intradermal injection sites have all been used
  • Studies have shown that there is little difference between areolar injections and peritumoral injections:
    • But a randomized controlled trial:
      • Suggested that areolar intradermal injections:
        • Have the highest rates of localization and decreased harvest time of the first sentinel lymph node
  • In tumors that are large and in the upper outer quadrant of the breast:
    • Peritumoral injection is probably superior
  • In patients who undergo nipple-sparing mastectomy:
    • Subareolar injection should be avoided
  • Skin tattooing:
    • Can occur with intradermal injection
• Patients with early-stage invasive breast cancer (clinically T1 and T2):
  • Who do not have clinically positive lymph nodes (cN0):
    • Should undergo SLNB
• The ASCO reviewed the literature and created guidelines for the use of SLNB:
  • The current ASCO guidelines for SLNB are displayed in the second table
• SLNB is widely applicable:
  • But there are some circumstances:
    • In which it is contraindicated
    • And others in which its utility is questionable
  • Given the dermal and pervasive lymphatic involvement in inflammatory carcinoma:
    • An ALND should be performed in patients with inflammatory cancer:
      • These patients have lymphatic vessels largely obstructed by tumor emboli:
        • Making sentinel node localization unreliable with high false negative rates:
          • Even after neoadjuvant chemotherapy (NAC)
  • Patients with large or locally advanced breast cancers (clinically T3 / T4):
    • Have historically:
      • Not been offered SLNB
    • Small case series have shown a large variability in:
      • The accuracy (85% to 98%) and a false negative rate (3% to 18%) of SLNB for patients with large tumors:
        • And these patients made up a small group in large, randomized sentinel lymph node clinical trials
    • Clinically node-negative patients with large tumors:
      • Also have high rates of positive SLNB as well as additional involved nonsentinel lymph nodes:
        • Ranging from 40% to 80%
      • Although many practitioners perform SLNB for patients with clinically T3 tumors;
        • Current ASCO guidelines argue that there is still insufficient evidence to support the practice

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• A physical examination alone:
  • Cannot accurately predict the presence of axillary disease
• The accuracy of a physical examination to detect axillary metastasis:
  • Ranges from 61% to 68%:
    • When compared with resection
• Ultrasonography, magnetic resonance imaging, and positron emission tomography–computed tomography:
  • Have all been used to evaluate the axilla:
    • And although these imaging modalities may improve on physical examination:
      • They are not as accurate as lymphadenectomy for small deposits:
        • And have a higher rate of false positives
• A level I and II axillary lymph node dissection (ALND):
  • Has been the gold standard:
    • For evaluating the extent of axillary disease
  • Unfortunately, the incidences of:
    • Lymphedema, chronic pain, seroma development, future cellulitis, numbness, and limits to mobility:
      • Are all significant sequelae following ALND
• Approximately 70% of patients who are clinically node negative:
  • Will have no evidence of disease detected with ALND:
    • Putting these patients needlessly at risk for complications
• In 1991, the technique of sentinel lymph node biopsy (SLNB) was proposed as an alternative to ALND in breast cancer patients:
  • The development of SLNB has now replaced ALND:
    • As a highly accurate and less morbid axillary staging procedure for most patients

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• A physical examination alone:
  • Cannot accurately predict the presence of axillary disease
• The accuracy of a physical examination to detect axillary metastasis:
  • Ranges from 61% to 68%:
    • When compared with resection
• Ultrasonography, magnetic resonance imaging, and positron emission tomography–computed tomography:
  • Have all been used to evaluate the axilla:
    • And although these imaging modalities may improve on physical examination:
      • They are not as accurate as lymphadenectomy for small deposits:
        • And have a higher rate of false positives
• A level I and II axillary lymph node dissection (ALND):
  • Has been the gold standard:
    • For evaluating the extent of axillary disease
  • Unfortunately, the incidences of:
    • Lymphedema, chronic pain, seroma development, future cellulitis, numbness, and limits to mobility:
      • Are all significant sequelae following ALND
• Approximately 70% of patients who are clinically node negative:
  • Will have no evidence of disease detected with ALND:
    • Putting these patients needlessly at risk for complications
• In 1991, the technique of sentinel lymph node biopsy (SLNB) was proposed as an alternative to ALND in breast cancer patients:
  • The development of SLNB has now replaced ALND:
    • As a highly accurate and less morbid axillary staging procedure for most patients

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• A thorough history and careful examination:
  • Help determine the extent of clinical disease in a patient with breast cancer
• The examination is best done:
  • With the patient seated:
    • Arms removed from the gown and relaxed at the side
  • The examiner then palpates the axillary soft tissue beneath the relaxed arm:
    • Pressing it against the chest wall, where lymph nodes can be felt as they roll across the firm surface
  • Feeling beneath the lateral border of the pectoralis major muscle and high up along the thoracic outlet:
    • Can reveal important clinical findings
  • The axillary contents should also be assessed with the patient supine:
    • And the arm above the head
  • The presence or absence of palpable axillary metastasis determines further management

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• Mammary analog secretory carcinoma (MASC):
  • Is a recently described salivary gland tumor:
    • That was likely classified as acinic cell carcinoma in the past
• The tumor has striking histologic and molecular similarities:
  • To secretory carcinoma of the breast
• Secretory carcinoma of the breast (SC):
  • Has shown to have a recurrent balanced chromosomal translocation:
    • t(12;15) (p13;q25):
      • Which leads to an oncogenic fusion gene ETV6-NTRK3
  • This translocation is also present in MASC:
    • This fusion gene encodes a chimeric tyrosine kinase:
      • That is known to play an important role on its oncogenesis
• Immunohistochemical similarities between MASC and SC of the breast also include:
  • Being S100 protein, epithelial membrane antigen (EMA), and vimentin positive and “triple negative” (ER/PR/Her2 negative)
• MASC predominantly affects:
  • Men and normally does not behave in an aggressive biology
• The parotid gland is the most common affected gland by MASC

• The official terminology of this entity:
  • Is now “secretory carcinoma”
• At the histologic level:
  • Tumor cells have eosinophilic or clear bubbly cytoplasm:
    • They may grow as tubules or microcysts, papillae, or macrocysts
  • Secretions are almost always present:
    • In the microcysts and / or macrocysts
• MASC characteristically harbors:
  • A balanced chromosomal translocation (12, 15):
    • Resulting in the formation of the ETV6–NTRK3 fusion genes
• Even though they have similar growth rate between MASC and ACC:
  • MASC is more likely to metastasize to the regional lymph nodes:
    • It should be considered as a more aggressive tumor compared with the regular low grade ACC
• MASC usually presents as a painless:
  • It is a non-tender mass that increases in size overtime
• The majority of MASC arise from the parotid gland;
  • Accounting for two thirds of the reported cases
• The mean age for presentation of MASC is 47 years:
  • In contrast with SC of the breast that usually occurs in younger patients
• MASC:
  • Is considered a low-grade carcinoma with a favorable prognosis:
    • According to Skálová et al:
      • It has moderate risk for local recurrence (15%)
      • Lymph node metastases (20%)
      • Low risk for distant metastases (5%)

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• Epithelial-myoepithelial carcinoma (EMC):
  • Is another typically indolent salivary gland tumor:
  • That is characterized by a multi-nodular pattern and biphasic or bilayered arrangement of inner ductal cells and outer myoepithelial cells, with classically clear cytoplasm
• EMC:
• Is a rare tumor with low malignant potential:
  • Accounting for less than 1 % of salivary neoplasms
• Peak incidence occurs in seventh decade:
  • With a predilection for female
• As early as 1956, EMC was reported as:
  • Adenomyoeipthelioma, clear cell adenoma, tubular solid adenoma and clear cell carcinoma:
    • Due to its varied histopathologic appearance
• The term EMC was coined by Donath et al. in 1972:
  • This discrete entity was subsequently incorporated in WHO classification of salivary gland tumors in 1991
• On histopathologic examination:
  • It shows dual cell population:
    • Composed of luminal ductal epithelial cells (inner layer) surrounded by large polygonal clear myoepithelial cells (outer layer):
      • Due to bidirectional differentiation of the stem cell
• The most common location is the parotid gland:
  • Also the index case has parotid involvement:
    • But it is also known to occur in submandibular gland and minor salivary glands of palate, base of tongue and rarely in breast, lung, kidney, uterus
• Rarely, it may show high grade transformation of epithelial or myoepithelial component:
  • Resulting in aggressive behavior
• Because of rarity of EMC a standard treatment guideline is not yet known:
  • Surgical resection is the most widely used approach:
    • Although, some of the reported cases have utilized post-operative radiotherapy (PORT) extrapolated from other salivary gland histologies
• Although it is a low grade tumor:
  • Local recurrence rates of 23% to 50 % have been reported:
    • With 25 % chance of distant metastasis
  • Local recurrence in as early as 6 months post operatively has been seen
• Histopathologic markers such as:
  • Solid growth pattern, nuclear atypia, DNA aneuploidy, necrosis, positive surgical margins and high proliferative activity:
    • Have been identified by some authors to be associated with more aggressive behavior and high frequency of local recurrences and metastases
• Surgery alone may not be sufficient in cases with histopathologic markers of aggressive behavior:
  • These patients may be candidates for PORT

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• Acinic cell carcinomas (AcCC):

• Is the second most common malignant tumor:

• Involving the parotid gland

• They represent 15% of malignant parotid gland neoplasms

• AcCC accounts for approximately:

• 5% to 17% of all salivary gland tumors:

• 10% to 17% of all malignant salivary gland tumors

• The parotid gland is composed almost exclusively of serous type acini:

• And it is the most common site of AcCC:

• 80% to 90% of cases

• Other reported sites are:

• The palate (up to 15%)

• Submandibular gland (4%)

• Sublingual gland (1%)

• AcCC occurs most often in the fifth decade of life:

• Women are affected more often than in men (ratio 3:2)

• It is generally a low-grade carcinoma:

• With indolent behavior

• Recurrences are usually delayed:

• Sometimes after decades:

• In a series reported by Ellis et al:

• 12% of tumors recurred and 8% metastasized (bone, lung, and brain)

• The regional lymph nodes:

• Were the most common site of metastases:

• Spafford et al:

• Reported cervical lymphadenopathy to be present in 10% to 15% of cases of AcCC

• Spiro et al:

• In a series of 67 cases with AcCC treated before 1968, identified five cases (7.5%) with cervical metastases at the time of initial treatment

• It is interesting that this tumor is the most common bilateral malignant salivary gland neoplasm:

• Although its bilateral presentation is not nearly as common as the bilateral presentations of benign tumors:

• Warthin’s tumor and pleomorphic adenoma

• AcCC:

• Are typically encased in a fibrous capsule:

• Grossly resembling round circumscribed nodules with a tan surface

• The cut surface is solid but may show cystic degeneration and hemorrhage

• Histologically, there are five cell types:

• Serous acinar cells:

• Explaining the predilection for the parotid gland

• Cells with clear cytoplasm

• Intercalated ductal cell

• Nonspecific glandular cell

• Vacuolated cell

• The microscopic recognition of AcCC also requires a strong appreciation for its varied growth patterns:

• There are four histologic growth patterns:

• Solid

• Microcystic

• Papillary

• Follicular

• Caution must be taken not to misread the:

• Solid pattern as normal parotid parenchyma

• The papillary-cystic pattern as cystic mucoepidermoid carcinoma

• The follicular pattern as metastatic thyroid carcinoma

• Serous acinar differentiation:

• Is developed most fully in the acinic cell:

• These cells have dark round nuclei and granular purplish cytoplasm

• The diagnosis of AcCC may be difficult to establish:

• Especially when some other cell type dominates the histopathology picture

• Some examples of this are the predominance of clear cells might cause confusion with:

• Mucoepidermoid carcinoma, clear cell adenocarcinoma, and metastatic renal cell carcinoma:

• In these circumstances, the diagnostic acinic cells can be identified using a periodic acid-Schiff (PAS) reagent:

• Their cytoplasmic secretory granules are PAS positive and diastase resistant

• Overall survival has been crudely estimated to be about 84%:

• Survival at 5 years has been reported between 76% to 90%, but fell to 56% at 20 years:

• Emphasizing the need for long- term follow-up