Overview

1. Large and Irregular Nuclei:

   • Appearance: Nuclei are often much larger than normal, with irregular shapes, and take up a greater portion of the cell (high nuclear-to-cytoplasmic ratio). They may appear darker than normal (hyperchromasia).
   • Mechanism: Caused by increased DNA content due to errors in cell division and ongoing mutations, leading to genomic instability and altered nuclear structure.

2. Prominent and Irregular Nucleoli:
   

   • Appearance: The nucleoli (structures within the nucleus) are often enlarged, more numerous, and irregularly shaped.
   • Mechanism: Reflects increased ribosome production needed for the high protein synthesis rates required by rapidly dividing cells.

3. Variation in Cell Size and Shape (Pleomorphism):

   • Appearance: Cancer cells within a tumor often vary significantly in their overall size and shape, unlike uniform normal cells.
   • Mechanism: Results from ongoing genetic mutations and a breakdown of normal cellular structural controls.

4. Loss of Differentiation (Anaplasia):

   • Appearance: Cells lose the specialized features of their normal counterparts and appear more primitive.
   • Mechanism: Genetic changes disrupt the normal developmental programs that control cell specialization.

5. Disorganized Arrangement & Loss of Polarity:

   • Appearance: Cells lose their normal orderly arrangement within tissues and their typical orientation.
   • Mechanism: Caused by alterations in cell adhesion molecules and the proteins that maintain tissue structure and cell orientation, allowing for chaotic growth.

6. Increased and Abnormal Cell Division (Mitoses):

   • Appearance: More cells are seen actively dividing, and these divisions may be abnormal (e.g., tripolar spindles).
   • Mechanism: Cancer cells bypass normal cell cycle controls due to mutations in regulatory genes, leading to uncontrolled and often faulty cell division.

7. Invasive Growth (Implied Feature):

   • Appearance: While not a single cell feature, evidence of cells infiltrating surrounding normal tissues is a hallmark.
   • Mechanism: Cancer cells gain the ability to break down tissue barriers and migrate, driven by changes in adhesion, motility, and enzyme production.

Classic examples

• Glioblastoma Multiforme (GBM):
  • Pseudopalisading necrosis: Tumor cells line up around areas of necrosis.
  • Endothelial proliferation.
  • GFAP positive.
• Meningioma:
  • Whorled pattern of cells.
  • Psammoma bodies: Laminated calcifications.
• Medulloblastoma:
  • Small, round, blue cells.
  • Homer-Wright rosettes: Circular grouping of tumor cells around a central fibrillary space.
• Pilocytic Astrocytoma:
  • Rosenthal fibers: Eosinophilic, corkscrew-shaped glial filaments.
  • Cystic lesion with a mural nodule.
• Oligodendroglioma:
  • "Fried egg" appearance: Cells with round nuclei, clear cytoplasm, and distinct cell borders.
  • "Chicken-wire" capillary pattern.
• Schwannoma:
  • Antoni A areas: Densely cellular areas with Verocay bodies (palisading nuclei around an acellular zone).
  • Antoni B areas: Less cellular, myxoid areas.
  • S-100 positive.
• Hodgkin Lymphoma (Nodular Sclerosing type):
  • Reed-Sternberg cells: Large, multinucleated or bilobed ("owl-eye") cells with prominent eosinophilic nucleoli.
  • Lacunar cells: Variant of Reed-Sternberg cells in a clear space (lacuna).
  • Fibrous bands dividing lymphoid tissue into nodules.
• Burkitt Lymphoma:
  • "Starry sky" appearance: Sheets of lymphocytes (dark sky) interspersed with benign macrophages containing apoptotic bodies (stars).
  • Associated with t(8;14) translocation (c-myc).
• Multiple Myeloma:
  • Clock-face chromatin in plasma cells (eccentric nucleus, basophilic cytoplasm, perinuclear pale zone - Golgi).
  • Rouleaux formation of RBCs (not a tumor cell feature but often seen).
• Papillary Thyroid Cancer:
  • "Orphan Annie eye" nuclei: Cells with empty-appearing nuclei due to finely dispersed chromatin and nuclear grooves.
  • Psammoma bodies.
  • Papillary architecture.
• Medullary Thyroid Cancer:
  • Nests or sheets of polygonal or spindle cells.
  • Amyloid deposits in the stroma (Congo red positive with apple-green birefringence).
• Small Cell Lung Cancer:
  • Small, dark blue cells with scant cytoplasm (Kulchitsky cells).
  • Nuclear molding, high mitotic rate.
  • Neuroendocrine origin (Chromogranin A, synaptophysin positive).
• Squamous Cell Carcinoma (general):
  • Keratin pearls: Concentric layers of squamous cells with keratinization.
  • Intercellular bridges.
• Adenocarcinoma (general):
  • Gland formation (acini, tubules).
  • Mucin production (may see signet ring cells if intracellular mucin displaces nucleus).
• Renal Cell Carcinoma (Clear Cell type):
  • Cells with abundant clear cytoplasm (dissolved glycogen and lipids).
  • Often arranged in nests with a rich vascular network.
• Wilms Tumor (Nephroblastoma):
  • Triphasic pattern: Blastemal (small, round, blue cells), stromal, and epithelial (abortive tubules/glomeruli) components.
• Basal Cell Carcinoma (Skin):
  • Nests of basaloid cells with peripheral palisading of nuclei.
  • Stromal retraction.
• Melanoma:
  • Atypical melanocytes with large, irregular nuclei, prominent nucleoli, and often melanin pigment.
  • Nests or individual cells invading the epidermis and/or dermis.
  • S-100, HMB-45, Melan-A positive.
• Colorectal Adenocarcinoma (often from adenomatous polyp):
  • Dysplastic glandular structures.
  • May show "dirty necrosis" in the glandular lumen.
• Serous Cystadenocarcinoma (Ovary):
  • Psammoma bodies are common.
  • Papillary formations.
• Endometrial Carcinoma (Endometrioid type):
  • Back-to-back glands with little intervening stroma.
• Prostate Adenocarcinoma:
  • Crowded glands lacking basal cell layer.
  • Prominent nucleoli.
• Ewing Sarcoma:
  • Small, round, blue tumor cells.
  • Sheets of uniform cells.
  • Associated with t(11;22) translocation.
• Osteosarcoma:
  • Malignant osteoblasts producing osteoid (immature bone).
  • Pleomorphic cells.