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Thomas, Md Associate Professor Section of Dermatopathology Valencia Thomas, Md Ut Houston School of Medicine Associate Professor Mohs and Dermasurgery Unit M.D

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Thomas, Md Associate Professor Section of Dermatopathology Valencia Thomas, Md Ut Houston School of Medicine Associate Professor Mohs and Dermasurgery Unit M.D 11/7/2016 HISTOPATHOLOGY OF SQUAMOUS CELL CARCINOMA VALENCIA THOMAS, MD ASSOCIATE PROFESSOR SECTION OF DERMATOPATHOLOGY VALENCIA THOMAS, MD UT HOUSTON SCHOOL OF MEDICINE ASSOCIATE PROFESSOR MOHS AND DERMASURGERY UNIT M.D. ANDERSON CANCER CENTER DERMATOPATHOLOGY, UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON DIRECTOR, MOHS SURGERY, M.D. ANDERSON CANCER CENTER Duplicate or Distribute Not Actinic Squamous Invasive Keratosis cell squamous Do carcinoma in- cell situ carcinoma 1 11/7/2016 ACTINIC KERATOSIS ATYPICAL KERATINOCYTIC PROLIFERATIONS • Actinic keratosis (AK) • “precancer” • Partial-thickness keratinocytic atypia • “squamous cell carcinoma grade 1/2” • Squamous cell carcinoma in-situ • “SCC – AK type” • Full-thickness keratinocytic atypia • Invasive squamous cell carcinoma • “keratinocytic intraepithelial neoplasia = KIN” • Well-differentiated • Does not need Mohs surgery • Moderately-differentiated • Poorly-differentiated • AK and squamous cell carcinoma are often • Other modifiers multifocal with field effects in margins • Depth of invasion, perineural invasion, lymphovascular • 1/20 develop into a skin cancer invasion, Duplicate KERATINOCYTIC INTRAEPITHELIAL AK: PARTIAL-THICKNESS ATYPIA NEOPLASIA = KIN 1, 2, 3 or • Analogous to CIN, PIN, VIN 1,2,3 • Really in SKIN with most popular system, we don’t have a “2”: AK = KIN-1 SCC in situ (Bowen’s) = KIN-3 Distribute ACTINIC KERATOSIS RX AK: PARTIAL-THICKNESS ATYPIA • Treating AKs is beyond this lecture • Trying to eradicateNot totally is like playing “whack a mole” so goal is to eradicate most significant areas • Cryo, curettage, laser, imiquimod, fluorouracil, Dodiclofenac, etc 2 11/7/2016 AK BUDDING INTO THE PAPILLARY DERMIS AK Duplicate or Hyperkeratotic “hypertrophic” AK = HAK, not invasive SCC Acantholytic actinic keratosis Distribute SQUAMOUS CELL CARCINOMA IN-SITU (SCCIS, BOWEN’S DISEASE)) Not • Full-thickness atypia • Disordered epidermis Do • Cannot tell which way is “up” • Loss of the entire granular layer 3 11/7/2016 Bowen’s disease = SCC in situ Duplicate or Clear cell Bowen’s disease – Pagetoid cells Bowen’s disease = SCC in situ resemble Paget’s disease or Melanoma Distribute Not Do 4 11/7/2016 INFLAMMATORY LESIONS • May have reactive atypia Duplicate Lichenoid keratosis or Distribute Not Do 5 11/7/2016 Unzipping of the dermal-epidermal junction INTERFACE DERMATITIS Parakaratosis Wedge-shaped hypergranulosis • Interface dermatitis • Lichenoid Lichen Planus Duplicate SPONGIOTICorDERMATITIS • Intercellular edema • Lymphocytes • Eosinophils may be present Distribute PSORIASIFORM DERMATITIS • Psoriasiform epidermal acanthosisNot • Suprapapillary plate thinning • Neutrophils • DoConfluent parakeratosis 6 11/7/2016 PERI-INFUNDIBULITIS • Rosacea • Dilated vessels throughout the reticular dermis • Perivascular and peri-infundibular lymphocytes with some plasma cells • Slight spongiosis Duplicate INVASIVE SQUAMOUS CELL CARCINOMA SCC or • 200,000 to 300,000 in the United States yearly • Surgical excision is the recommended • Seventy-five percent of these tumors occur on the head and neck treatment for uncomplicated cutaneous SCCs • Risk factors for the development of SCCs • Cure rates above 95 to 98 % with Mohs • Excessive ultraviolet radiation, older age, male sex, chemical exposure (arsenic), chronic ulcers, fair skin, blond Micrographic Surgery (MMS) or red hair, blue eyes and chronic scarring conditions Distribute INVASIVE SCC HISTOLOGY TYPES SCC Not • Well-differentiated • Metastatic rate: 3% to 5% usually to • Moderately-differentiated regional lymph nodes • Poorly-differentiated • 10 to 20% of high-risk SCC metastasize Do • Adenoid (acantholytic) • Spindle cell 7 11/7/2016 Nests of squamous epithelial cells Abundant eosinophilic cytoplasm Large, vesicular nucleus Prominent intercellular bridges Duplicate or Distribute SQUAMOUS CELL CARCINOMA: Not CYTOLOGY • Nests, sheets and strands of squamous epithelial cells • Abundant eosinophilic cytoplasm • Large, often vesicular, nucleus • Prominent intercellular bridges Do • Variable keratinization 8 11/7/2016 INTERCELLULAR BRIDGES (SPINES) • Cohesive aggregates of tumor • Keratinization Duplicate or Distribute Irregular chromatin (dark and light) HISTIOCYTES Cords of cells High nuclear/cytoplasmic ratio Not Absence of lumens Do • Note the even chromatin • Absence of spines • Multinucleated cells SQUAMOUS CELL CARCINOMA • Low nuclear/cytoplasmic ratio 9 11/7/2016 Well- Poorly differentiated differentiated SCC SCC Duplicate or Acantholyic or pseudoglandular SCC Distribute Spindle cell SCC Not Do 10 11/7/2016 Spindle cell (sarcomatoid) SCC Duplicate SINGLE CELL SEEDING or • Single dyscohesive squamous cells in dermis indicate poor prognosis and high chance of metastasis Distribute Not Do 11 11/7/2016 Duplicate or Distribute MOHS MICROGRAPHIC SURGERY (MMS) Not Tissue-sparing excision technique Evaluation of 100% of the peripheral and deep margin Employed only for certain tumors displaying Do contiguous growth 12 11/7/2016 PERMANENT PROCESSING AGGRESSIVE TUMORS AND MOHS MICROGRAPHIC SURGERY (MMS) The specimen is sectioned vertically (breadloafed) and placed in paraffin • 2% to 5% of tumors recur after MMS due to Depth of invasion may be measured aggressive behavior or residual disease Nerves/Vessels can be evaluated • Post- or preoperative therapy with radiation therapy or chemotherapy may be indicated Duplicate HIGH-RISK CUTANEOUS SCC : GREATER THAN 5% CHANCE OF SUBCLINICAL METASTASES or • Aggressive histologic features • Poorly-differentiated • Recurrence tumor histology • Involvement of deep tissues • Perineural invasion • Greater than 2mm in depth • Host immunosuppression • Occurrence in prior scars • Solid-organ transplant • Large tumor size greater than 2 patients cm • Leukemia or lymphoma • Location in high-risk areas • Human Immunodeficiency Virus) Distribute Not Do Farasat et al. J Am Acad Dermatol. 2011 Jan 19. [Epub ahead of print] 13 11/7/2016 METASTASIS FROM SQUAMOUS CELL CARCINOMA • Sun-exposed 0.5% • Lower lip 10% • Chronic leg ulcers20% • Burn scars 20% • Irradiated sites 20% • Osteomyelitis 30% Duplicate HIGH-RISKor SCC • Metastatic rates of tumors larger than 2 cm may be triple those of lesions less than 2 cm • Invasion of the tumor greater than 4mm and beyond the subcutis also independently correlates with an increased risk of GREATER THAN 2 MM, MAY BE OF CLINICAL subclinical metastases CONCERN IF ONE OTHER HIGH RISK FEATURE IS PRESENT Distribute HIGH-RISK FEATURES CLARK LEVEL GREATER THAN IV • Breslow depth > 2 mm thickness • Clark level greaterNot than IV • Clark Level IV • Cancer in the • Perineural invasion reticular dermis • Greater than Clark • Primary location on the ear or nonglabrous lip Level IV • Cancer in the • Poorly differentiated or undifferentiated fat and beyond Do• Patient immunocompromise • Locally recurrent tumors http://www.cancer.gov/images/cdr/live/CDR630443-571.jpg 14 11/7/2016 CLARK LEVEL > IV Duplicate NERVE CYTOLOGYor PERINEURAL INVASION Distribute IDENTIFYING NERVES Not Artefactual split between nerve layers on frozens Do 15 11/7/2016 PERINEURAL Epineurium PERINEURAL INVASION (PNI) DEFINITION Around the nerve Perineurium • Tumor cell invasion in, around, and through nerves1 Endoneurium • Tumor cells within any of the 3 layers of the nerve sheath or tumor foci outside of the nerve with involvement of 33% of the nerve’s circumference2 1. Batsakis JG. Nerves and neurotropic carcinomas. Ann Otol Rhinol Laryngol 1985;94(4 Pt 1):42. 2. Liebig C, Ayala G, Wilks JA, et al. Perineural invasion in cancer: a review of the literature. Cancer 2009;115:3379-91. http://www.conncad.com/gallery/myelin.html Duplicate or Endoneurium Endoneurium Epineurium Epineurium PERINEURAL Around the nerve Distribute ESTIMATING 0.1 MM (100 MICRONS) GENERAL CONSIDERATIONS • Tumor incidentally • Identify normal, Not engulfing a nerve adjacent nerves under (Incidental PNI) the central mass of • Tumors that seek-out tumor • Eccrine coils have an outer diameter of 50 – 80 microns nerves (clinically- • Look at the significant PNI) morphology of the entire mass (bird’s eye Do view) 16 11/7/2016 CLUES TO ASSESS PNI • Inflammation • Tears in the deep dermis/subcutis • Small-caliber nerve invasion (SCNI) of nerves • Levels (additional sections) less than 0.1mm in diameter was associated with significantly lower risks of disease- specific death, local recurrence, nodal metastasis, distant metastasis, and all-cause death • PNI defined as tumor cells within the nerve sheath Dermatol Surg 2009;35:1859–1866 Duplicate ESTIMATING NERVE DIAMETER WITH ECCRINE Nerve Engulfment COIL DIAMETER • Diameter ranges from or 50 to 80 microns • Small caliber nerves (less than 0.1 mm) are about the same size or SCC smaller than the NERVE dermal eccrine coil (outer diameter) Dermatol Surg. 2014 May;40(5):497-504. Distribute Neurotropic tumor SKULL BASE Not NERVE Do J Neurosurg. 2015 Apr 24:1-8 17 11/7/2016 SKULL BASE TUMORS • Median overall survival (n=24) 43.2 months • 82% 1-year • 37% 5-year Duplicate SCCor Distribute Not Do 18 11/7/2016 ADJUNCTIVE THERAPY FOR HIGH-RISK, INVASIVE SCC AFTER EXCISION: • Radiation therapy (RT) • Positive surgical margins • Multiple recurrences • Perineural/intraneural invasion • Invasion of the cartilage • Invasion of the bone • Systemic chemotherapeutic agents for metastatic disease • Intralesional therapies • 5-fluorouracil • Standard dosing regimens and duration have yet to be clarified Duplicate GRANULOMATOUS INFLAMMATION GRANULOMATOUSor INFLAMMATION Palisaded Sarcoidal/ Naked Tubercle
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