Neoplasms Neoplasms-3 Non-epithelial tumors • Benign borderline/intermediate malignant 1 - Leiomyoma • (locally malignant 2 - Lipoma 3 - Liposarcoma • or rarely metastasizing) 4 - Chondrosarcoma 5 - Meningioma 6 – Glioblastoma (multiforme glioblastoma) • Epithelial epithelial • Non epithelial non epithelial

Benign v/s malignant neoplasm Nomenclature

Benign tumours: by attaching the suffix –oma to the Benign Malignant cell type from which the tumor arises Nonepithelial tumours Local invasion No Yes • Fibrous tissue – fibroma Distant metastases No Yes • Bone – osteoma Angioinvasion No Yes • Vascular tissue – angioma Growth Slow Rapid • Cartilage – chondroma Capsule Almost always yes No Epithelial tumours Local recurrences No Yes • Adenoma: benign epithelial neoplasm producing gland patterns or derived from glands. Morphology Well differentiated Anaplastic Cystadenoma: adenoma with cyst formation (ovary) Angiogenesis Small Numerous vessels • Papilloma: benign epithelial neoplasms growing on Heterogeneity Small Very big any surface and producing finger-like projection

Leiomyoma Cellular atypia/Anaplasia Leiomyoma is a common benign neoplasm derived from smooth muscle. It predominantly arises in the uterine body, less commonly in uterine cervix, • Pleomorphic cells has been found sporadically in other localizations (e.g. skin, nipples) • Extremely hyperchromatic (darkly stained) nuclei Uterine leiomyomas, known also as myomas or fibroids frequently occur • Nuclear-cytoplasmatic ratio 4:1 (normally 1:1) during the reproductive period (may be present even in about 75%- usually • Giant cells 30-50% of females of reproductive age) and tend to regress • Bizarre nuclei (large and various in size and in postmenopausally. shape) They are often multiple. According to their topography, leiomyomas of • Coarse and clumped chromatin uterine body can be subdivided into: intramural (occur within the • Prominent/nucleoli myometrium); submucosal (just beneath the endometrium); subserosal (just beneath the serosa). • Numerous mitoses Subserosal and submucosal leiomyomas • Atypical mitoses may be pedunculated and in certain • Loss of normal polarity circumstances undergo torsion with subsequent haemorrhagic necrosis

1 Leiomyoma Leiomyoma Microscopical examination reveals mature smooth myocytes arranged in Uterine leiomyomas, even when they are intertwining bundles (Fig.1) Observed in some tumors variations in size, extensive, may be asymptomatic. shape and staining properties of the cells as well as degenerative changes The most important symptoms are (Fig.2) have no diagnostic nor prognostic value produced by submucosal leiomyomas (abnormal bleeding), compression of the bladder, sudden pain if disruption of blood supply occurs, and impaired fertility

Macroscopically leiomyomas are sharply circumscribed (but unencapsulated), discrete, round, firm, gray-white tumors varying in size from a few milimeters to several centimeters Fig.2 Fig.1

Leiomyoma showing well-differentiated, regular, spindle-shaped smooth muscle cells.

Lipoma Lipoma Lipomas - benign tumors of fat, are the most common soft tissue tumor of adulthood. They are subclassified according to particular morphologic features as: • Lipoma – the commonest benign *conventional lipoma, *fibrolipoma, nonepithelial tumor in adults *angiolipoma, *spindle cell lipoma, *myelolipoma, and *pleomorphic lipoma The conventional lipoma, the most common subtype arises in the subcutis of the proximal extremities and trunk (also in mediastinum, retroperitoneal space or internal viscera)

MA: conventional lipoma is a well-encapsulated, soft, yellowish mass

Lipoma Nomenclature

MI: composed of mature adipocytes, it hardly differs from contiguous Malignant neoplasms adipose tissue

Conventional lipoma Mesenchymal origin – sarcomas Angiolipoma • Fibrous tissue origin – fibrosarcoma • Chondrocytes origin – chondrosarcoma • Vascular origin – angiosarcoma Epithelial origin – carcinomas • With glandular pattern – adenocarcinoma • Encapsulated • Mature adipocytes and many capillaries • Adipocytes with slight variation in • With squamous pattern – squamous size and shape (no pleomorphism) cell carcinoma

2 Liposarcoma Liposarcoma Liposarcomas are the most common sarcomas (malignant mesenchymal neoplasms) in adults They tend to occur in the deep soft tissues of the retroperitoneum and proximal extremities Clinically, it remains asymptomatic for a long period and at time of diagnosis usually presents as a large mass invading widely the adjacent tissues, not uncommonly with distant metastases

MI: liposarcomas can be divided into: well-differentiated, myxoid, round cell, and pleomorphic variants. The cells in well-differentiated liposa. are readily recognized as lipocytes. In the other variants, most of the tumor cells are not obviously adipogenic, but some cells indicative of fatty differentiation are almost always present. These cells are known as lipoblasts; they mimic fetal fat cells and contain round clear cytoplasmic vacuoles of lipid that scallop the nucleus.

Liposarcoma Liposarcoma MI: myxoid liposa. - composed of primitive mesenchymal cells (they show atypia and many abnormal mitoses) in a prominent myxoid stroma with characteristic branching vascular pattern

Myxoid liposarcoma with abundant myxoid ground substance in which are scattered adult-appearing fat cells and Elongated, thin vessels more primitive cells, some containing small lipid vacuoles (lipoblasts).

• Plastic Surgery Key Humpath.com In most cases of the myxoid and round cell variant of liposarcoma there is a chromosomal abnormality t (12;16)- a translocation involving the long arm of chromosome 12 and the short arm of chromosome 16

Liposarcoma Chondroma

surgical specimen: retroperitoneal myxoid Chondromas are benign tumors of hyaline cartilage. They may arise within the medullary cavity, where they are known as enchondromas, or on the surface of liposarcoma 14 x 9 cm bone, where they are called subperiosteal or juxtacortical chondromas. Enchondromas are the most common of the intraosseous cartilage tumors, and are usually diagnosed in patients between age 20 and 50. They are found in the small bones of the hands or feet and in sternum and ribs. MA: presents as a lobulated grayish, translucent mass, usually well delimited, arising within bone. MI: the tumor closely resembles normal hyaline cartilage. Abundant, slightly basophilic show numerous lacunar spaces which, however, are distributed ununiformely. Neoplastic cells which are similar to normal chondrocytes are both dispersed in cartilaginous matrix or lie within lacunae (more than two cells in one lacunar spaces). There is no atypia

3 Chondrosarcoma

Normal cartilage v. neoplastic one Chondrosarcoma is a malignant chondromatous neoplasm, most commonly arising in pelvic and shoulder girdles, vertebral column, distal end of femoral bone and proximal end of tibial bone. Siuma.eduSium It predominantly affects men in their fourth and fifth decades. Grossly, chondrosa. forms a mass of variable size, poorly delimited, arising either centrally within bone or beneath the periosteum. On cut surface it is lobular, glassy, translucent and exhibits evident invasion of bone and, if advanced, adjacent soft tissues.

Histological examination reveals chondroid texture with rather scanty matrix and irregularly distributed neoplastic cells, often arranged in sheets or clusters. These cells have hyperchromatic, often multiple nuclei. Numerous mitoses can be seen.

Meningioma Chondrosarcoma Meningiomas are predominantly benign tumors usually attached to the dura, that arise from the meningothelial cell of the arachnoid.  They may be found along any of the external surfaces of the brain as well as within the ventricular system, where they arise from the stromal arachnoid cells of the choroid plexus. are predominantly benign intracranial neoplasms of arachnoidal origin Molecular Genetics The most common cytogenetic abnormality is loss of chromosome 22, especially the long arm (22q). The deletions include the region of 22q12 that harbors the NF2 gene, which encodes the protein merlin; as expected, meningiomas are a common lesion in the setting of NF2. Clinical Features  Meningiomas are usually slow-growing lesions that present either with vague nonlocalizing symptoms or with focal findings referable to compression of underlying brain. Anaplastic chondrocytes within a chondrosarcoma  They are uncommon in children and generally show a moderate (3 : 2) female predominance

Meningiomas – location Meningioma Meningiomas are usually solitary (but when present at multiple sites, especially in („Clinically malignant” neoplasms) association with neuromas or glial tumors, a diagnosis of NF2 should be considered) They are usually rounded masses with well-defined dural bases that compress underlying brain but are easily separated from it (Fig. A). The surface of the mass is usually encapsulated with thin, fibrous tissue. Gross evidence of necrosis or extensive hemorrhage is not present.

MA: presents as a firm, solid mass of well-defined borders, usually attached to the dura. It compresses and displaces the brain but does not invade

4 155 - Meningioma 155 - Meningioma MI: tumor is composed of fusiform cells with uniform nuclei, arranged in onion-skin- like whorls. Locally, there are deeply basophilic lamellated depositions of calcium salts, designates as „psammoma bodies”, and reflecting degeneration and dystrophic calcification of central areas of the whorls

Meningiomas: composed of whorled nests of cells or spindled forming short fascicles

Various histologic patterns are observed, with no prognostic significance. These include syncytial, fibroblastic, transitional, psammomatous, secretory, microcystic. Xanthomatous degeneration, metaplasia (often osseous), and moderate nuclear pleomorphism are common in meningiomas. Among these lesions, proliferation index has been shown to be a predictor of biologic behavior. Psammomatous meningioma with a whorled pattern of cell growth and psammoma bodies

Meningioma

Atypical meningiomas are lesions with a higher rate of recurrence and more aggressive local growth, and may require radiation therapy in • The brain has specialized interstitial cells called addition to surgery. They are distinguished from lower grade meningiomas glia. by the presence of either a mitotic index of four or more mitoses per 10 • They play reparative, supportive and metabolic high power fields (≥ 4/HPF) or at least three atypical features role. (increased cellularity, small cells with a high nuclear-to-cytoplasmic ratio, prominent nucleoli, patternless growth, or necrosis). • There are three kinds of glial cells: – Astroglia (astrocytes) and Anaplastic (malignant) meningioma is a highly aggressive tumor with the – Oligodendrocytes – of ectodermal origin appearance of a high-grade sarcoma, but retaining some histologic – Microglia – mesodermal evidence of meningothelial origin. Mitotic rates are often extremely high – Ependymal cells line the cerebral ventricles (>20 mitoses per 10 high power fields).

Astrocytomas – brain tumors derived from astrocytes (type of glial cells) Several different categories of astrocytomas are recognized - e.g. fibrillary (diffuse) astrocytoma, glioblastoma, pilocytic astrocytoma Diffuse astrocytomas and glioblastomas account for about 80% of adult primary brain tumors. TargetHealthGlobal Usually found in the cerebral hemispheres, they may also occur in the cerebellum, brainstem, or spinal cord, most often in the fourth through • Astrocytes form a glial “scar” composed of cellular sixth decades. processes, but do not produce collagen ! The most common presenting signs and symptoms are epileptic seizures, • Oligodendrocytes are the CNS equivalent of Schwann headaches, and focal neurologic deficits related to the anatomic site of cells and produce myelin involvement. • Microglia – phagocytosis The prognosis for patients with glioblastoma is very poor. With current optimal treatment, consisting of resection followed by radiation therapy and chemotherapy, the mean length of survival after diagnosis has • Tumors may derive from each kind of glial increased to 15 months; 25% of such patients are alive after 2 years. cells (Robbins and Cotran; Pathologic basis of disease, 2010)

5 MA: poorly defined, gray, infiltrative tumor that expands and distorts the invaded brain; range Glioblastoma (glioblastoma multiforme) in size from a few centimeters to enormous lesions that replace an entire hemisphere. In glioblastoma, variation in the gross appearance of the tumor from region to region is MI: ► high cellularity (increase in the number of glial cell nuclei), characteristic. Some areas are firm and white, others are soft and yellow (the result of tissue ► nuclear pleomorphism, necrosis), and yet others show regions of cystic degeneration and hemorrhage. The tumor ► necrosis- often in a serpentine pattern occurs in areas of hypercellularity may appear well demarcated from the surrounding brain tissue, but infiltration beyond the with highly malignant tumor cells crowded along the edges of the necrotic outer margins is always present. regions, producing a histologic pattern referred to as pseudopalisading ►vascular or endothelial cell proliferation- is characterized by tufts of piled- up vascular cells that bulge into the vascular lumen

Fig. A, Computed tomographic (CT) scan of a large tumor in the cerebral hemisphere showing signal enhancement with contrast material and pronounced peritumoral edema. B, Glioblastoma multiforme appearing as a necrotic, hemorrhagic, infiltrating mass. Glioblastoma-foci of necrosis with pseudopalisading of malignant nuclei

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