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• Definition and origin:
  • It is the most common variety of visceral STS. These tumors are believed to originate from the interstitial cells of Cajal within the gastrointestinal myenteric plexus and emanate from nearly any part of the alimentary tract, from esophagus to anus.
• Sites:
  • The most prevalent GIST sites are the stomach, the small bowel, and the rectum.
  • Cajal cells are thought to function as pacemaker cells in the viscera, mediating contractions.
• Markers:
  • Cajal cells and GIST share common markers for CD117 and a calcium-activated chloride channel called DOG1.
  • CD117 is another name for the KIT gene, which codes for a tyrosine kinase transmembrane receptor called c-kit.
  • These molecular descriptions led to dramatic refinements in the diagnosis and treatment of patients with GIST.
  • In morphologic appearance, GIST is classically a spindle cell neoplasm of smooth muscle origin.
  • Although these tumors were previously described as leiomyoma or leiomyosarcoma, GISTs are differentiated on the basis of:
    • CD34, CD117, and DOG1 expression and the lack of smooth muscle staining.
• The c-kit receptor is a proto-oncogene that belongs to the platelet-derived growth factor receptor (PDGFR) superfamily.
• The natural c-kit ligand is a stem cell factor, and its binding causes tyrosine kinase receptor homodimerization, autophosphorylation, and activation of multiple pathways, including RAS, RAF, MAPK, AKT, and STAT3.
• Certain mutations of the c-kit receptor confer constitutive activation of the receptor, which ultimately results in cellular proliferation.
• The other relevant gene, also found on chromosome 4, that bears striking similarity to c-kit is the PDGFRα.
• Prevalence:
  • Overall, about 70% of GISTs have KIT gene mutations, approximately 7% have PDGFRα mutations, and 15% have wild-type KIT and PDGFRα genotypes.
  • These GISTs are characterized by a number of other mutations affecting succinate dehydrogenase (SDH), BRAF, KRAS, and NF1.
  • SDH mutations are related to GIST in patients affected by the Carney-Stratakis syndrome.

• The differential diagnosis for a papillary lesion:
  • Discovered on FNA is broad:
    • FNA is often not able to reliably distinguish between benign, atypical, in situ, or invasive lesions
  • Even if core needle biopsy can be performed:
    • Papillary lesions often require surgical excision for complete characterization
• The wide range of pathologic terms involving the word “papillary” leads to confusion:
  • And there is a spectrum of malignant potential among papillary lesions
• Therefore, proper identification is key to the treatment approach: 
  • Intraductal papilloma (IDP), 
  • IDP with atypia
  • IDP with ductal carcinoma in situ (DCIS)
  • Papillary DCIS
  • Papillary carcinoma
  • Invasive micropapillary carcinoma

• Intraductal papilloma:
  • Is a benign, circumscribed, intraductal proliferation:
    • Which can be categorized as:
      • Central IPD
      • Peripheral IDP
  • Central IDP:
    • Often presents as nipple discharge
  • Peripheral IDP:
    • The condition of multiple peripheral IDPs is also referred to as papillomatosis
  • IDP with atypia is similar to atypical ducal hyperplasia (ADH):
    • In that there is architectural and cytologic atypia:
      • That fails to meet criteria for DCIS
    • When it does meet this threshold:
      • It is termed papilloma with DCIS
  • Papillary DCIS
    • Which is fundamentally DCIS:
      • That has prominent papillary architecture:
        • It does not arise within an IDP
  • Papillary carcinoma:
    • Is uncommon:
      • Accounts for only 1% to 2% of all breast cancers
    • It is more often found in older women
    • Presents as a central circumscribed mass:
      • Bloody nipple discharge is common
    • Papillary carcinoma of the breast can be further classified as:
      • Encapsulated or solid types:
        • Both of which have an excellent prognosis
  • Invasive micropapillary carcinoma:
    • Is a type of ductal cancer
    • With a growth pattern consisting of numerous small pseudo-papillary clusters of cells
    • It is an aggressive form of breast cancer:
      • That is most often high grade with frequent lymphatic involvement
• References:
  • Tse GM Ma TK, Lui PC, Ng DC, Yu AM, Vong JS, et at. Fine needle aspiration cytology of papillary lesions of the breast: how accurate is the diagnosis? J Clin Pathol. 2008;61(8):945-949.
  • Jorns JM. Papillary lesions of the breast: a practical approach to diagnosis. Arch Pathol Lab Med. 2016;140(10):1052-1059
  • Yang Y, Liu B, Zhang X, Fu L. Invasive micropapillary carcinoma of the breast: An update. Arch Pathol Lab Med. 2016;140(8):799-805.

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #BreastCancer #IntraductalPapilloma #IDP #PapillaryLesionsoftheBreast

• Age is a very strong predictor of outcome:
  • In differentiated thyroid cancer
• Nearly 2/3 of the patients are younger that 55 years of age
  • They have a great long term survivorship:
    • Nearly 100% at 20 years

• The majority of patients with thyroid cancer are women:
  • In this study from MSKCC
    • 73% of the cases were in women
• Women have a slightly better 20 year survival (96%) compared to men (87%)

• 94% of patients had papillary thyroid carcinoma with a very good longterm survival (93.7%) compared to follicular (87.9%) and Hurthle cell carcinomas (88%)

• In this study from MSKCC 92% of the patients had tumors less than 4 cm in size:
  • Tumors less that 4 cm in size had an excellent long term survival (95.2%) compared to tumors larger than 4 cm (74.5%)

• Gross extra-thyroid extension (ETE) only occurs in a minority of patients (9%):
  • This patients have a worse overall survival (74.9%) compared intra-thyroidal tumors (95.9%) and tumors with microscopic (96.6%) extra-thyroidal extension

• Lymph node metastasis in general has a negative impact in long term survival:
  • However this difference is relatively small:
    • 96.2% in node negative patients vs. 89.2% in node positive patients
  • Studying the effect of lymph node metastasis in thyroid cancer survival:
    • Lymph node metastasis only had an adverse effect on survival in older patients (older than 55 years):
      • There is a progressive decline in disease specific survival as the years go bye
  • Young patients with and without nodal metastasis have excellent long term survival

• Distant metastasis will have an impact on long term survival:
  • Fortunately only 1.9% of differentiated thyroid cancers with present with distant metastasis

• Only stage II patients with an ATA high risk category will have a a progressive increase in mortality as the years pass.

• The surgical outcome between total thyroidectomy and lobectomy is comparable when compared for:
  • Local recurrence free survival
  • Neck recurrence free survival
  • Distant recurrence free survival
  • Disease specific survival
  • Overall survival

• What to do if the differentiated thyroid cancer is located to the isthmus and the lateral lobes are normal and no lymph node metastasis?
  • Is simple isthmusectomy the appropriate procedure?

• When to perform more that a total thyroidectomy?
  • Gross extra thyroidal extension (anteriorly or posteriorly)

• An R0 resection is fundamental when operating for gross extrathryoidal extension and performing more than a total thyroidectomy:
  • Patients in which an R0 resection can be performed will have long term survival exceeding 95% compared to patient with an R1 resection (60%)
  • R1 or R2 resections leads to a 40% decrease in survival

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• Accessory breast tissue:
  • Is an isolated parenchymal mass without a nipple-areolar complex
  • It occurs due to failed regression of primitive mammary tissue
  • It most often occurs in the axilla
• Unlike the tail of Spence;
  • Which is a normal extension of breast tissue to the underarm:
    • Accessory breast tissue of the axilla is not functionally connected to the breast
• Accessory breast tissue:
  • Is normal breast tissue
  • Is subject to the same benign and malignant conditions that can occur in the breast
• Ultrasound is the primary modality for evaluation:
  • Accessory breast tissue:
    • Can appear as either:
      • A purely glandular elements
      • Fibrous elements or 
      • A mixture of fibrous and glandular elements
• The mediolateral oblique (MLO) view on mammogram:
  • Is the best for imaging the lower aspect of the axilla and the axillary tail of the breast
• On breast magnetic resonance imaging (MRI):
  • Accessory breast tissue:
    • Can appear as a subcutaneous, poorly defined lesion that has contrast enhancement and signal intensity similar to the breast but is discontiguous with the rest of the breast parenchyma

• References:
  • Kulkarni D, Dixon JM. Congenital abnormalities of the breast. Women’s Health, 2012;8(1):75–88.
  • Lim HS, Kim SJ, Baek JM, Kim JW, Shin SS, Seon HJ, et al. Sonographic findings of accessory breast tissue in axilla and related diseases. J Ultrasound Med. 2017:36(7):1469-1478.
  • Patel BK, Jafarian N, Abbott AM, Khazai L, Lee MC. Imaging findings and management of primary breast cancer in accessory axillary breast tissue. Clin Breast Cancer. 2015 Aug;15(4):e223-9.

#Arrangoiz #BreastSurgeon #AccessoryBreastTissue #SurgicalOncology #CancerSurgeon #BreastCancer #Miami #Mexico

• The breast develops from the ectodermal “mammary ridge” or the “milk-line”:
  • Which extends from the future axilla to the groin
• The nipple and areola:
  • Develop from the ectoderm along the milk-line
• The majority are seen in the inframammary region
• Accessory nipples:
  • Are seen in 1% to 5% of the population although differences among ethnic groups can occur
  • The incidence is the same between male and females
  • They are prone to the same diseases as normal nipples but do not require an excision or treatment:
    • Unless the nipple cause irritation or cosmetic issues

• References:
  • Kulkarni D, Dixon JM. Congenital abnormalities of the breast. Women’s Health.2012;8(1):75–88.
  • Brown J, Schwartz RA. Supernumerary nipples: an overview. Cutis 2003:71(5):344–346.

#Arrangoiz #BreastSurgeon #BreastCancer #AccessoryNipples #CancerSurgeon #SurgicalOncologist #Miami #Mexico #Teacher

• There are multiple types of papillary breast lesions including:
  • Benign intraductal papillomas
  • Atypical papillomas
  • Papillomas with atypical ductal hyperplasia (ADH)
  • Papillary carcinomas
• A solitary intraductal papilloma:
  • Is a common breast lesion:
    • That can present with nipple discharge if arising in the large ducts, or
    • As a clinically occult mass on imaging if occurring in the periphery
    • Infrequently, an intraductal papilloma presents as a palpable mass
  • Typically, atypia or carcinoma in situ:
    • Is more frequently associated with intraductal papillomas in the periphery of the breast:
      • However, due to intralesional heterogeneity and fragmentation, sampling error is a concern with core needle biopsy
  • Recent studies suggest the risk of upgrade to carcinoma upon excision of an intraductal papilloma with atypia:
    • Is 21% to 37%:
      • Thus, removal of the entire lesion is sometimes required to rule out in situ or invasive cancer
  • A wide margin is not required at the time of excision biopsy of a papillary lesion
  • References:
    • Racz JM, Carter JM, Degnim AC. Challenging atypical breast lesions including flat epithelial atypia, radial scar, and intraductal papilloma. Ann Surg Oncol. 2017;24(10): 2842-2847.
    • Wei S. Papillary lesions of the breast: an update. Arch Pathol Lab Med. 2016;140(7):628-643
    • Swapp RE, Glazebrook KN, Jones KN, Brandts HM, Reynolds C, Visscher DW, et al. Management of benign intraductal solitary papilloma diagnosed on core needle biopsy. Ann Surg Oncol. 2013;20(6):1900-1905.
    • Cheng TY, Chen CM, Lee MY, Lin KJ, Hung CF, Yang PS, et al. Risk factors associated with conversion from nonmalignant to malignant diagnosis after surgical excision of breast papillary lesions. Ann Surg Oncol. 2009;16(12):3375-3379.
    • Ko D, Kang E, Park SY, Kim SM, Jang M, Yun B, et al. The management strategy of benign solitary intraductal papilloma on breast core biopsy. Clin Breast Cancer.2017;17(5):367-372.

#Arrangoiz #BreastSurgeon #BreastExpert #CancerSurgeon #SurgicalOncologist #BreastCancer #BreastNodule #IntraductalPapilloma #Miami #Mexico

• Rapidly and definitively establish the diagnosis:
  • Because ATC is a highly dedifferentiated cancer that retains few characteristics of noncancerous thyroid cells, attaining a definitive diagnosis can be challenging, yet critical
  • Time is also of the essence because of the very rapid growth rate of ATC and due to the importance of early intervention in minimizing catastrophic airway compromise
  • Differential considerations / mimics can include:
    • Primary thyroid lymphoma
    • SCC of the head and neck
    • Metastatic cancer:
      • Especially from lung
  • Early assessment of tumor mutations is key in expanding therapeutic options
  • Attain multidisciplinary team engagement and coordination:
    • Coordinate early multidisciplinary involvement of surgeons, radiation and medical oncologists, endocrinologists, and palliative care teams to arrive at options for best care
  • Determine extent of disease:
    • Staging with imaging is required to classify as stage IVA, IVB, IVC:
      • This is best done with FDG PET/CT and / or alternatively with dedicated body CT or MRI.
    • Extent of local invasion must also be evaluated in parallel to assist in surgical decision-making, and requires laryngoscopy
  • Undertake patient counseling to establish individualized patient goals of care:
    • Counseling must be provided by a team / individuals skilled in the surgical, medical, and palliative management of complex thyroid malignancies in which trade-offs counterbalancing risks and benefits with goals of care are completely discussed
    • This counseling should best involve not only the patient but also involve supportive individuals / family members
  • Evaluate Surgical Options:
    • The primary goals in stages IVA and IVB ATC patients within an aggressive approach to their care are:
      • Complete resection and prompt transition to adjuvant definitive-intention therapy:
        • As long-term survival may be attainable
      • Thus, surgical procedures should not generate a wound or result in complications:
        • That would prevent chemotherapy and radiation onset due to the risk of wound breakdown given the lack of data supporting an association between increased extent of surgery and improved survival outcomes
    • In IVC ATC, the limited benefit resulting from surgery must be carefully tempered in consideration of other available palliative approaches, including:
      • Radiation and systemic therapy
  • Surgical decision-making:
    • Rapidly assess resectability:
      • Determining tumor invasion of the larynx, trachea, esophagus, and status of the major vessels of the neck
    • Consider the need for tracheotomy, extent of thyroidectomy, neck dissection, and the need to avoid laryngectomy, esophageal resection, and major vessel reconstruction
    • Balancing morbidity from surgery with expected benefits within the context of patient-anticipated prognosis and individualized goals of care is paramount
    • Considerations:
      • Performance score / status.
      • Presence of distant metastasis
      • Extent of local invasion of trachea and esophagus
      • Need for urgent tracheostomy, understanding that placement of a tracheostomy results in immediate improvement in upper airway obstruction but requires significant education for care and understanding that tumor location and growth may make management of the tracheotomy complex.
      • Patient goals of care and willingness to accept anticipated morbidity of planned surgery
  • Nonsurgical management decision-making:
    • Other than surgery, options may include postoperative or primary chemoradiation versus palliative radiotherapy, systemic therapy, or best supportive care considered within the context of:
      • Patient goals of care and willingness to accept anticipated toxicities of presented options.
      • Patient performance status and comorbidities and their impacts on feasibility of planned care.
      • Trade-offs from one approach to care versus alternatives
      • Keep hospice / end-of-life care discussions in the foreground
      • Given the historically dire prognosis of ATC, especially if stage IVC, hospice should always be presented among care options:
        • Truth telling and realistic presentation of anticipated prognosis are critical in allowing sound patient decisions within their individual goals of care
        • For some patients, hospice may be preferable—even from the outset—in comparison with other alternative care options

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In Graves’ disease, thyroid-stimulating antibodies are produced, causing overproduction of thyroid hormones, leading to hyperthyroidism. A blood test to check for these antibodies helps diagnose Graves’ disease.

• Efficacy for medullary thyroid cancer (MTC):
  • Was evaluated in 55 adult and pediatric (older than 12 years) patients with advanced or metastatic RET-mutant MTC:
    • Who had previously been treated with cabozantinib, vandetanib, or both:
      • The ORR was 69%
  • In addition, the drug was evaluated in 88 patients with advanced or metastatic RET-mutant MTC:
    • Who had not received prior treatment with cabozantinib or vandetanib:
      • The ORR for these patients was 73%
  • The trial also enrolled 19 patients with RET-positive thyroid cancer whose condition was refractory to radioactive iodine (RAI) treatment and who had received another prior systemic treatment:
    • The ORR was 79%
  • Eight patients had received only RAI:
    • The ORR for these patients was 100%
• In all the cases of thyroid cancer:
  • Among the patients who responded to treatment:
    • The response lasted longer than 6 months
• RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers
• A fact sheet from the company notes that RET mutations are found:
  • In about 60% of sporadic MTC cases
  • In over 90% of familial MTC cases
  • RET fusions are found in approximately 10% to 20% of papillary thyroid cancers
• The approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET
• In the LIBRETTO-001 trial:
  • The rate of discontinuations because of adverse reactions (ARs) was 5%
  • The most common ARs, including laboratory abnormalities (≥ 25%), were:
    • Increased aspartate aminotransferase level
    • Increased alanine aminotransferase level
    • Increased glucose level
    • Decreased leukocyte count
    • Decreased albumin level
    • Decreased calcium level
    • Dry mouth
    • Diarrhea
    • Increased creatinine level
    • Increased alkaline phosphatase level
    • Hypertension
    • Fatigue
    • Edema
    • Decreased platelet count
    • Increased total cholesterol level
    • Rash
    • Decreased sodium levels
    • Constipation
  • The most frequent serious AR (≥ 2%) was:
    • Pneumonia
• The FDA warned that selpercatinib can cause:
  • Hepatotoxicity, elevation in blood pressure, QT prolongation, bleeding, and allergic reactions
  • It may also be toxic to a fetus or newborn baby so should not be taken by pregnant or breastfeeding women
• The drug is currently being assessed in two phase 3 confirmatory trials:
  • LIBRETTO-531 involves treatment-naive patients with RET-positive MTC.

• ATA Guidelines in Anaplastic Thyroid Carcinoma:
  • Work-up:
    • Immediate diagnosis is essential
    • The biopsy should undergo molecular evaluation:
      • Including:
        • BRAF V600E mutation
    • Airway assessment is paramount
    • Staging including anatomic imaging (head to toe)
  • Role of surgery:
    • Only 10% of patients present with local disease that is resectable
    • Local disease:
      • Compete resection is standard
    • Neoadjuvant therapy (targeted therapy) followed by surgery when feasible:
      • Local regional disease that is borderline resectable or un-resectable with actionable mutations:
        • BRAF V600E mutation, ALK fusions, TRK fusion
        • CHEK point inhibitors
    • Palliative resection (rare indication)
    • Open biopsy for diagnosis:
      • When FNA or core needle biopsy is undetermined
  • Advance local disease:
    • Indication for tracheostomy:
      • First we must have an educated discussion with the patient:
        • Discuss prognosis
        • Concerns
        • Airway signs and symptoms
        • Wishes

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