Pathology Notes

Practice questions Benign white cell disorders © Jun Wang, MD, PhD 1. Use this case for next two questions . A 1-year-old white boy presents with recurrent pharyngitis for 4 months. His past history is otherwise unremarkable. Physical examinations reveal normal development. His weight and height are about 65 percentile. No significant abnormalities are seen except redness of his pharynx and bilateral tonsillar swollen. Laboratory tests reveal normal range hemoglobin and platelets. His absolute neutrophil count is 400/mm 3  (normal > 1500/ mm 3 ). Quantity of other white cells are within normal range. Peripheral blood smear reveal no significant morphological atypia. Bone marrow biopsy reveal normal cellularity with trilineage maturation. No dysplasia is identified. What is the most likely diagnosis? A. Autoimmune neutropenia B. Benign ethnic neutropenia C. Megaloblastic anemia D. Myelodysplastic syndrome E. Myeloproliferative neoplasm 2.   A 1-year-old white

Practice questions answers Benign white cell disorders © Jun Wang, MD, PhD 1. A. This case is characterized by neutropenia with increased risk of infection, as shown in this patient with recurrent pharyngitis. Benign ethnic neutropenia is seen in some African descendent and does not carry an increased risk for infection. Absence of morphological atypia, dysplasia and anemia make it unlikely to be megaloblastic anemia, or myelodysplastic syndrome (MDS) . Myeloproleferative neoplasms (MPN) are characterized by peripheral cytosis, not cytopenia. 2. B. Autoimmune neutropenia is likely associated with autoantibodies againt human neutrophil antigen 1. Abnormal activation of tyrosine kinases can be associated with variable disorders, including MPN . Folate acid and vitamin B12 deficiency are associated megaloblastic anemia. Single nucleotide polymorphism at Duffy antigen receptor is seen in benign ethnic neutropenia . Ineffective hematopoiesis of stem cells are associated wit

Infectious mononucleosis Updated: 09/10/2020 © Jun Wang, MD, PhD General features Febrile illness EB virus associated Spread by intimate contact, including breast feeding, saliva exchange and other sexual contacts Human likely major reservoir More common in young adults Higher risk for EBV associated malignancies, such as Hodgkin lymphoma , Burkitt lymphoma Clinical presentations Most asymptomatic Incubation 1-2 months Triad of fever , tonsillar pharyngitis , and lymphadenopathy Other nonspecific presentations: fatigue, Hepatomegaly, jaundice, splenomegaly, etc Risk of fatal spontaneous spleen rupture Key pathogenesis EB virus infection of B cells Infects reticular endothelial system (liver, spleen, lymph nodes, etc) through circulation B cells produce antibodies against EBV protein components T cells eliminate infected B cells Inflammatory reactions associated with clinical presentations B cell malignancy may develop due to uncontrolled proliferatio

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