TABLE 17-3.

Organelle Approach to Tumor Diagnosis

Organelle	Features	Tumor
Basal lamina	50- to 100-nm–thick, moderately dense layer following the contours of the cell membrane	Epithelium, mesothelium, meningothelium, granulosa cell, Sertoli cell, muscle, nerve sheath, adipose, and endothelial tumors. (Not present in: hematopoietic cells, fibroblasts, neurons, chondrocytes, osteoblasts, myofibroblasts)
Extracellular matrix	Collagen: Cross-striated periodicity of 50 nm, 50- to 100-nm-thick. Elastin: Amorphous, moderately dense component and 10- to 12-nm tubular filaments in different arrangements. Proteoglycans: Poorly stained, amorphous with occasional granular to filamentous structures.	Numerous epithelial and mesenchymal tumors. Chondrosarcoma. Variable in mesenchymal tumors.
Fibronexus	Cell-to-matrix structure composed of fibronectin filaments in the extracellular space and subplasmalemmal plaques with intracellular smooth muscle myofilaments. Difficult to observe in formalin-fixed tissues.	Myofibroblastic tumors. (Not present in smooth muscle tumors and fibrosarcomas)
Filaments, intermediate	About 10 nm thick. Located in cytoplasmic matrix. Noncytokeratin: vimentin, desmin, neurofilaments, glial filaments. Impossible to distinguish them by EM. Variable amounts; between organelles, forming bands of spheroidal masses. Cytokeratins: tonofibril (bundles of cytokeratin filaments). Loosely organized (nonsquamous epithelium e.g., mesothelium) or high electron density (squamous and basal cell epithelium).	Carcinomas, neuroendocrine tumors, melanomas, sarcomas. Squamous, basal cell, mesothelioma, endocrine, ameloblastoma, synovial, and epithelioid sarcomas. Myoepithelium (along with myofilaments).
Filament, smooth muscle	5- to 7-nm (actin) and 15-nm (myosin) thick with dense bodies and attachment plaques.	Leiomyosarcoma, hemangiopericytoma, myoepithelium, myofibroblast.
Filaments, striated muscle	Variable degree of differentiation (organization) of sarcomeric myofilaments (actin, myosin).	Rhabdomyosarcoma, rhabdomyoma.
Glycogen	Small, pale to dense particles (30 nm) or rosettes (100-200 nm). Empty areas of cytoplasm due to extraction during processing.	Muscle and liver tumors. Variable amount in many carcinomas and sarcomas.
Golgi apparatus	Packaging and biochemically altering proteins produced in RER. Stacks of membranes.	No specific tumor types.
Intercellular junctions	Desmosomes: uniform width of 20-30 nm with intermediate linear density, subcytoplasmic membrane plaques and tonofilaments. Gap junctions: Closely apposed membranes (2-nm space) without associated filaments or dense material.	Many epithelial and mesenchymal tumors.
Lipid	Not membrane-bound with amorphous to lamellar, variably dense matrix. Membrane-bound if in lysosomes.	Abundant in steroidogenic tumors, adipose tumors, sebaceous carcinoma, renal cell carcinoma.
Melanosomes	Rod-shaped or elliptical, 200-600 nm, single membrane granules.	Melanoma, melanocytic schwannoma.
Melanosome, compound	Aggregates of melanomes within secondary lysosomes. Variable stages of digestion.	Keratinocytes, macrophages, fibroblasts.
Microtubules	Long, cytoplasmic, 25-nm diameter tubules.	Abundant in neuronal and neuroendocrine tumors.
Mitochondria	Rounded, ovoid, rod-shaped, elongated, branched, annular (1000-nm width). Two limiting membranes and intermediate clear space. Cristae represent infoldings of inner membrane. Tubular or tubulovesicular cristae in cells with lipid and SER indicate steroidogenic phenotype (liver, adrenal cortex, Leydig, and ovarian cells).	Abundant in oncocytomas, hepatocellular tumors, renal cell carcinoma, steroid and muscle tumors.
Mucin granules	Single limiting membrane granules with flocculent, filamentous, reticulate, or homogeneous matrix with no halo.	Mucinous carcinomas.
Neuroendocrine granules	Location: below plasma membrane, within basal cytoplasm and cell processes. Size: Typical 200-400 nm, with range from 60 to 1000 nm. Center: very dense matrix (core) separated from the membrane by clear halo. Small granules (80-150 nm) Large granules (1000 nm) Norepinephrine granules: eccentric cores Biphasic (rounded and rod-shaped profiles) granules Crystal-like granules and sometimes multiple cores	Neuroendocrine, paraneuronal, neuronal tumors. Retinoblastoma, neuroblastoma, Merkel cell tumor Pituitary gland tumors Pheochromocytomas, paragangliomas Abdominal and urogenital neuroendocrine tumors Insulinoma
Nucleus	Nuclear irregularities are common in neoplastic cells. Artifact of sectioning with contained portions of cytoplasm (pseudoinclusions or nuclear pockets). Multilobation: multiple nuclear profiles connected by thin bridges. Multinuclearity: Nuclear profiles not joined.	Multiple tumor types. Nonspecific feature. Osteoclast-like giant cell tumors. Myeloid leukemia, large B-cell lymphoma.
Primary lysosomes	Small (100-300 nm), rounded, or oval, single-membrane–bound granules. Dense, homogeneous, granular matrix. Crystalline core in eosinophil granules.	Myeloid sarcomas, histiocytic sarcomas, follicular thyroid carcinoma. Endocrine and steroidogenic tumors, granular cell tumors.
RER	Common; active protein synthesis (immunoglobulins, matrix, neuroendocrine, lysosomes).	Fibrosarcoma, plasmacytoma, osteosarcoma.
SER	Common in cells rich in lipid, glycogen, or steroid metabolism.	Sex cord–stromal tumors, hepatocellular tumors.
Secondary lysosomes	Variably sized, single-membrane–bound organelles with remnants of digested material.	Granular cell tumor. Myeloid leukemias, histiocytic sarcoma, prostatic and neuroendocrine tumors.
Serous/zymogen granules	Large (up to 1000 nm), single membrane–bound with a dense to pale matrix and no halo.	Serous carcinomas (e.g., salivary, pancreatic)
Synaptic vesicles	40- to 80-nm, membrane-bound structures with clear interior	Differentiated neuronal tumors

RER, Rough endoplasmic reticulum.

SER, Smooth endoplasmic reticulum.