Pathology Notes

Practice questions Soft tissue tumors, except skin, cardiac and vascular tumors ©Jun Wang, MD, PhD 1. A 49-year-old woman presents with a soft mass at the upper outer quadrant of her left breast. She has a history of left breast ductal carcinoma in situ 2 years ago and was treated with surgery. She has type II diabetes and has BMI of 31 (normal18.5 to 24.9). Physical examination reveal a 1.5 cm soft mass under unremarkable skin. A 3.5 cm left breast scar is seen consistent with her history of surgery. The mass is resected and grossly it is yellow, soft with lobulated surface, covered by a fine thin capsule. Microscopically it is composed of cells with a large single intracellular clear vacuole and a very small round nucleus with condensed chromatin. No cytological atypia or fibrosis is seen. What is the diagnosis? A. Lipoma B. Myxoid liposarcoma C. Normal mature adipose tissue D. Recurrent ductal carcinoma in situ E. Well differentiated liposarcoma 2. Use this

Well differentiated liposarcoma   Updated: 02/27/2023 © Jun Wang, MD, PhD General features Called atypical lipomatous tumor if at periphery Most common subtype of liposarcoma Usually in age 40-60 Clinical presentations Most common location: lower limbs and retroperitoneum Key morphological features Relatively mature adipose tissue with focal cytological atypia Scattered lipoblast Markers S-100 Genetic abnormalities Ring or giant chromosome/rod chromosomes from 12q13-15 Amplification of MDM2 and CDK4 Back to soft tissue tumors Back to contents

Undifferentiated pleomorphic sarcoma Updated: 08/07/2020 © Jun Wang, MD, PhD General features High grade undifferentiated sarcoma Older term “Malignant Fibrous Histiocytoma” NOT proper anymore Usually age 50+ years, slightly more common in male Diagnosis of exclusion Clinical presentations Deep seated mass with progressive enlargement More common in lower extremities Key morphological features Markedly pleomorphic cells with necrosis and mitosis Markers Variable, usually inconclusive Treatment Excision Radiation Chemotherapy Back to soft tissue tumors Back to contents

Tumor like vascular lesions   Updated: 10/20/2020 © Jun Wang, MD, PhD Vascular malformations Salmon patch AKA nevus simplex Usually head and neck More common in face and neck P ersistent macular erythema Dilated dermal vessels, malformation, usually regress Clinical diagnosis Port-wine stain AKA nevus flammeus Flat, pink, red to purple Well demarcated May grow with age and thicken the skin surface If in distribution of trigeminal nerve may be associated with Sturge-Weber syndrome Clinical diagnosis Vascular ectasias Localized dilation of preformed vessels Spider telangiectasia   Radial, pulsatile array of dilated subcutaneous arteries or arterioles around a central core May be associated with hyperestrinism as seen in cirrhosis Hereditary hemorrhagic telangiectasia AKA Osler-Weber-Rendu disease Autosomal dominant Most commonly involves skin and mucosa  Irregular collection of blood vessels Localized capillary dilation with arterial blood shunted directly into postcapill

Synovial sarcoma Updated: 08/07/2020 © Jun Wang, MD, PhD General features Biphasic malignant tumor with both epithelial and mesenchymal components May be monophasic More common in young adults, male Clinical presentations Mass near large joint Most common sites: Knee and ankle Joint rarely involved Key morphological features Epithelial cells lining duct-like spaces Hyperchromic spindle cells in the background Monophasic: Only spindle cell components, that are positive for EMA Markers Positive for EMA and cytokeratin in both components Vimentin in spindle cells Genetic abnormalities t(X;18)(p11.1;q11): SYT-SSX1 fusion t(X;18)(p11.21;q11): SYT-SSX2 fusion genes Treatment Excision Radiation Poor prognosis indicators High grade, high proliferative index Necrosis SYT-SSX1 fusion Back to soft tissue tumors Back to contents

Superficial fibromatosis Updated: 08/107/2020 © Jun Wang, MD, PhD General features Benign proliferation of fibroblasts/myofibroblasts with an infiltrating pattern Different pathogenesis from deep fibromatosis , even with identical microscopic morphology More common in men Usually do not progress Clinical presentations Thickening or nodules, usually painless Commonly arising from superficial fascia May influence digit function if at palm or planta Three types Palmar fibromatosis (Dupuytren's contracture) Plantar fibromatosis (Ledderhose's disease) Penile fibromatosis (Peyronie's) Key morphological features Bipolar fibroblasts and myofibroblasts incollagenous stroma NO atypia Genetic abnormalities NO beta-catenin or APC mutation  Treatment Excision Incision to release contracture band Back to soft tissue tumors Back to contents

Schwannoma   Updated: 08/07/2020 © Jun Wang, MD, PhD General features Benign nerve sheath tumor arising from differentiated Schwann cells Most commonly 20 - 50 years old Majority are sporadic, may be associated with neurofibromatosis II (NF2) or Carney complex Clinical presentations Mass with abnormal sensation Commonly in limbs, especially upper limbs, head and neck Deep tumor commonly in posterior mediastinum or retroperitoneum Pathogenesis Abnormal activation of PI3K, RAS and RAC due to merlin inactivation Genetic abnormality Loss of function mutation of merlin at 22q12 Morphological features Encapsulated biphasic nerve sheath tumor Cellular component(Antoni A) that palisades (Verocay bodies), and myxoid component (Antoni B) Marker Positive for S100 Back to soft tissue tumors Back to contents

Rhabdomyosarcoma   Updated: 08/18/2021 © Jun Wang, MD, PhD General features Malignant soft tissue tumor with skeletal muscle differentiation Most common pediatric soft tissue sarcoma Clinical presentations Nontender mass Occasionally with overlying skin erythema Most common location: Head and neck, genitourinary tract, and the extremities Subtypes Embryonal rhabdomyosarcoma Alveolar rhabdomyosarcoma Pleomorphic rhabdomyosarcoma Anaplastic rhabdomyosarcoma Sclerosing rhabdomyosarcoma Mixed type Key morphological features Rhabdomyoblast: eccentric nuclei, granular cytoplasms, tadpole cells Markers Positive for myogenin, desmin, myoD1 Treatment Surgery Radiation Chemotherapy Prognosis Superior prognosis: botryoid, spindle cell Intermediate prognosis: embryonal Poor prognosis: alveolar, undifferentiated sarcoma Poor with FOXO1 gene fusion Back to soft tissue tumors Back to contents

Rhabdomyoma   Updated: 10/23/2020 © Jun Wang, MD, PhD General features Most common pediatric primary tumor of the heart Usually in patients less than 1 year of age Sporadic cases may be associated with other congenital heart diseases If cardiac, usually associated with tuberous sclerosis Rhabdomyomatosis : Multiple, usually less than 1 mm each Cardiac tumor may cause sudden cardiac death May regress spontaneously Clinical presentations Most common location: ventricular myocardium Symptoms associated with size, location and number of tumor: obstruction, arrhythmias, congestive heart failure Key morphological features Firm mass surrounded by normal tissue Nodules of large polygonal clear cells Intracellular vacuoles separated by strands of cytoplasm between cell membrane and nucleus (spider cells) Diagnostic approaches Echocardiography, MRI Biopsy/histological assessment Differential diagnoses Fibroma: May have calcification, dense fibroblast and co

Pleomorphic rhabdomyosarcoma Updated: 08/07/2020 © Jun Wang, MD, PhD General features High grade tumor composed of undifferentiated cells Rapid growth Usually in patients older than 50 Poor prognosis Clinical presentations Painless mass Most common location: lower extremity Key morphological features Bizarre cells No alveolar or embryonal components Markers Positive for myogenin, desmin, myoD1 Genetic abnormalities Complex karyotype Treatment Combination of surgery, radiation and chemotherapy Back to soft tissue tumors Back to contents

Pleomorphic liposarcoma Updated: 08/07/2020 © Jun Wang, MD, PhD General features High grade Median age 54-70 years Aggressive Recurrence/metastasis common Clinical presentations Most common location: thigh, trunk, limb girdles, etc Risk factors Radiation Neurofibromatosis Key morphological features Markedly atypical tumor cells with bizarre nuclei Lipoblast Mature adipose tissue Markers S-100 Genetic abnormalities Complex karyotype Treatment Wide excision/amputation Radiation therapy/chemotherapy Back to soft tissue tumors Back to contents

Nodular fasciitis Updated: 08/07/2020 © Jun Wang, MD, PhD General features Believed to be reactive proliferation of fibroblasts and myofibroblasts Usually young adults History of previous trauma Low risk of recurrence Clinical presentations Rapid growth, raising concern of malignancy Usually self-limited Most common sites: flexor arm, chest, back, etc Commonly arising from superficial fascia Key pathogenesis Probably a transient neoplasm Key morphological features Myxoid stroma Stellate and spindle cells separated by delicate collagen bundles Vascular proliferation Scattered inflammatory cells and extravasated red blood cells NO significant atypia Differential diagnosis Other sarcomas (high cellularity, necrosis, atypia, brisk mitosis, etc) Genetic abnormalities Balanced translocation t(17;22)(p13;q13) resulting in MYH9-USP6 gene fusion Treatment Excision Back to soft tissue tumors Back to contents

Neurofibroma Updated: 03/28/2020 © Jun Wang, MD, PhD General features Benign tumor with nerve sheath differentiation If multiple, likely associated with neurofibromatosis type 1 Malignant transformation rare Subtypes Plexiform: Irregularly expanded nerve bundles with nodular appearance, prominent myxoid matrix; associated with NF1 Diffuse cutaneous: Large plaque like elevation , typically NF1-associated Superficial cutaneous: Pedunculated nodules, solitary (sporadic) or multiple (likely NF1 associated) Clinical presentations Flesh-colored, soft nudule, solitary or multiple Slow growing, painless May have abnormal sensation (electric-like shock with light touch) Key morphological features Non-encapsulated spindle cell proliferation Thin slandering nuclei (coma like) Fibrillary background May be plexiform Markers Positive for S-100 May be focally positive for CD34 and Factor XIIIa Genetic abnormalities NF1 if neurofibromatosis Treatment

Myxoid liposarcoma   Updated: 08/18/2021 © Jun Wang, MD, PhD General features Used to be called myxoid/round cell liposarcoma More common 40-50s Adults in 20’s to 40’s Clinical presentations Most common location: Usually extremities, esp. proximal thigh Pathogenesis Deregulation of NF-kB pathway by FUS-DDIT3 chimeric protein Key morphological features Low grade: Myxoid background with mature adipocytes High grade: Sheets of round cells Delicate vasculature Lipoblast, less differentiated cells with round to oval dark nuclei Markers S-100 Genetic abnormalities FUD-DDIT3 Treatment Wide excision Raiotherapy/chemotherapy Poor prognostic factors Poorly differentiated (round cell) component Large size, necrosis, high Ki-67 index, p53 overexpression Back to soft tissue tumors Back to contents

Malignant peripheral nerve sheath tumor Updated: 08/07/2020 © Jun Wang, MD, PhD General features AKA: Malignant schwannoma, neurofibrosarcoma Commonly associated with neurofibromatosis (NF) 1 May arise de novo More common in adults May have history of radiation exposure May recur, distant metastases common Clinical presentations Deep seated tumor associated with major nerves Commonly location: Neck, forearm, lower leg, buttock Key morphological features Hyperchromic spindle cells Markers Positive for S-100, CD56 Negative for EMA, keratin (different from synovial sarcoma) Treatment Excision Radiation Chemotherapy Back to soft tissue tumors Back to contents

Liposarcoma Updated: 08/07/2020 © Jun Wang, MD, PhD General features Most common soft tissue sarcoma of adults More common in 40 + age Usually deep site, especially retroperitoneal Recurrence common Clinical presentations Soft mass Single or multiple Key morphological features Features of adipose tissue differentiation Cytological atypia Lipoblast : Cells with irregular dense nuclei and multiple intracellular lipid vacuoles Markers Positive for S-100, negative for HMB-45  WHO classification Atypical lipomatous tumour/well differentiated liposarcoma Dedifferentiated liposarcom a Myxoid liposarcoma/round cell liposarcoma Pleomorphic liposarcoma Liposarcoma, not otherwise specified Treatment Surgery Post-surgery radiation therapy Back to soft tissue tumors Back to contents

Lipoma Updated: 08/07/2020 © Jun Wang, MD, PhD General features Most common soft tissue tumor Benign Clinical presentations Single or multiple Soft mass Key morphological features Morphologically normal mature adipose tissue Fine fibrous capsule grossly or microscopically Treatment Excision Back to soft tissue tumors Back to contents

Leiomyosarcoma   Updated: 08/07/2020 © Jun Wang, MD, PhD General features Malignant tumor of smooth muscle Commonly in uterus, skin, subcutis, deep soft tissue and GI Third most common retroperitoneal sarcoma after liposarcoma and undifferentiated pleomorphic sarcoma Aggressive clinical behavior Most common metastasis site: lung Clinical presentations Mass Symptoms depending on location Key morphological features Large tumor Hypercellular, hyperchromic spindle cells Pleomorphic cells, usually marked cytological atypia Necrosis, active mitosis, atypical mitosis Markers Positive for desmin, smooth muscle actin Genetic abnormalities Complex, commonly p53 mutation and p16 overexpression Treatment Excision Chemotherapy Radiation Poor prognosis indicators Retroperitoneal, mesenteric or other deep location > 5 cm, except uterus > 65 years C-myc expression Back to soft tissue tumors Back to contents

Leiomyoma   Updated: 08/07/2020 © Jun Wang, MD, PhD General features Benign tumor of smooth muscle Commonly in uterus, skin, subcutis, deep soft tissue and GI If multiple: Leiomyomata Clinical presentations Mass Uterine leiomyoma may cause dysfunctional uterine bleeding or lower abdomen pressure-related symptoms Key morphological features Well circumscribed firm mass Bulging trabecular cut surfaces Bundles or fascicles of spindled cells with minimal atypia Cigar shaped nuclei Usually no necrosis, no mitosis Markers Positive for desmin, smooth muscle actin Genetic abnormalities HMGIC, HMGIY, MED12 for uterine leiomyoma Treatment Excision Back to soft tissue tumors Back to contents

Kaposi sarcoma   Updated: 10/21/2020 © Jun Wang, MD, PhD General features Likely arising from endothelial cells 4 types Epidemic AIDS-related Most common presentation of Kaposi sarcoma Incidence and severity reduced following the introduction of HAART CD4 count most important factor associated with KS development Early involvement of lymph nodes and gut and wide dissemination Relatively more aggressive May develop lymphoma or another second malignancy Classic, or sporadic More common in individuals from the Mediterranean basin and Central and Eastern Europe or their descendants  More common in male Higher risk if history of cancer (commonly non-Hodgkin lymphoma) or altered immune state, but NOT with HIV Mucosa of mouth and GI tract and regional lymph nodes may be affected Immunocompromised Occurs months to years after high-dose immunosuppressive therapy Skin or metastatic lesions present Skin lesions may regress if immunosuppression is stopped