Fibro & Soft Tissues PDF

Fibro & Soft tissues By: dr.sha3bani Fibrous Tissue Fibrous tissue primarily consists of fibroblasts (cells that produce fibers) and an extracellular matrix. The extracellular part is composed mainly of collagen fi...

Fibro & Soft tissues By: dr.sha3bani Fibrous Tissue Fibrous tissue primarily consists of fibroblasts (cells that produce fibers) and an extracellular matrix. The extracellular part is composed mainly of collagen fibers, which give the tissue strength, and elastin fibers, which provide flexibility. Muscle Tissue Muscle tissue contains two main protein filaments: Actin (thin filaments): These play a key role in muscle contraction and are paired with myosin. Myosin (thick filaments): These interact with actin filaments to facilitate movement and contraction. Adipose Tissue Adipose tissue, or fat tissue, comes in two main types: White Adipose Tissue: This is the most common, found under the skin, in the abdomen, and around organs. Its cells, called lipocytes, contain a large fat vacuole that can push the nucleus to the cell’s edge. Brown Adipose Tissue: This type is less common in adults. It contains multiple fat droplets and a central nucleus, and its primary role is to generate heat. Blood Vessels and Peripheral Nervous System Soft tissue tumors, which arise in non-epithelial tissue like blood vessels and peripheral nerves, are believed to originate from mesenchymal stem cells, not from mature cells of the same tissue. Unlike many tumors in the digestive system, which develop through a sequence of mutations, soft tissue tumors are typically malignant from the start rather than evolving from benign growths. Trauma is not a cause of these tumors. Causes of Soft Tissue Sarcomas Radiation: Can lead to soft tissue sarcomas, such as extraskeletal osteosarcoma. Foreign Objects: Implants, such as prostheses, may cause sarcomas to form around them. Viruses: Human herpesvirus 8 (HSV-8) is linked to Kaposi’s sarcoma, and Epstein-Barr virus (EBV) is involved in leiomyosarcoma or leiomyoma in immunocompromised patients. Genetics: Conditions like neurofibromatosis increase the risk of soft tissue tumors, including malignant peripheral nerve sheath tumors. Diagnosis of Soft Tissue Tumors Biopsy: An incisional biopsy (sampling part of the tumor) does not increase metastasis or recurrence. For malignant tumors, complete surgical removal is necessary to prevent any chance of remaining tumor cells spreading along the surgical path. Pathology: Typically, light microscopy is adequate for diagnosis. However, some tumors require additional markers or special tests for precise identification. Intraoperative Tumor Assessment During surgery, if the surgeon is unsure whether a tumor is benign or malignant, they can perform an intraoperative biopsy, which is sent to surgical pathology. This real-time assessment helps determine the tumor type, malignancy level, and whether the margins are clear (indicating complete removal). This step is crucial for various tumors, especially soft tissue types. Tumor Types and Age Associations Soft tissue tumors often correlate with specific age groups: Embryonal Rhabdomyosarcoma: Common in children. Synovial Sarcoma: More frequent in young adults. Liposarcoma: Often seen in middle-aged or older adults. Grading Tumors Tumors are graded based on certain criteria that predict aggressiveness: 1. Differentiation: How much the tumor resembles normal tissue. Score 1: Tumor resembles mesenchymal or fat tissue. Score 2: Distinct tissue type, less like normal tissue. Score 3: Unclear histologic type. 2. Mitosis: Frequency of cell division, with scores from 1-3. Score 1 for low, Score 2 for moderate, Score 3 for high mitotic activity. 3. Necrosis: Presence of dead tissue within the tumor. Score 1 for minimal necrosis, Score 2 for significant necrosis. Tumors with lower scores are considered low grade, while those with higher scores (especially in differentiation, mitosis, and necrosis) are intermediate or high grade, which is significant for prognosis. Tumor Staging and Prognosis Tumor prognosis depends on several factors: Size: Larger tumors generally indicate a worse prognosis. Depth: Deep-seated or peritoneal tumors often have poorer outcomes than superficial ones. Location: Tumors in the peritoneum tend to have worse prognoses than those on the skin. Genetic mutations, like TP53 or RB mutations, are linked with higher malignancy levels. Lipoma vs. Liposarcoma Lipoma: A benign fat tissue tumor, common in adults, often found in the neck or trunk and typically located just under the skin (subcutaneous). It has a capsule that helps distinguish it from surrounding tissue. Microscopically, lipomas resemble normal fat but may show secondary changes, like fat necrosis or calcification. These can sometimes make diagnosis challenging, as necrosis can mimic liposarcoma. Variants: Fibrolipoma (with fibrous tissue), angiolipoma (with blood vessels). Liposarcoma: A malignant fat tissue tumor, usually deeper and found between muscles or tendons. It lacks a capsule, distinguishing it from a lipoma. Tumor Appearance in Microscopy and Macroscopy Macroscopic: Lipomas appear as yellow, well-circumscribed masses with a capsule that clearly separates them from adjacent tissue. Microscopic: Lipocytes in lipomas resemble normal fat cells, and the presence of a capsule helps in diagnosis. Some lipomas contain blood vessels (angiolipomas) and fibrous tissue (fibrolipomas), aiding in further subclassification. Liposarcoma Overview Liposarcoma is the malignant counterpart of the benign lipoma. It is the most common soft tissue sarcoma (or neoplasm) in adults, particularly occurring in people between 50 and 60 years old. Common sites for liposarcoma include the proximal limbs (e.g., thighs) and the retroperitoneum (the area behind the abdominal cavity). Characteristics of Liposarcoma Boundaries: Liposarcomas typically have defined borders but lack a capsule, allowing them to invade surrounding tissues more than a lipoma. Microscopic Features: The defining cell type in liposarcoma is the lipoblast—a cell with one or more fat vacuoles in its cytoplasm, often with jagged nuclear borders. The nucleus may be pushed to the side or located in the center, giving it a distinctive appearance. Presence of lipoblasts helps differentiate liposarcomas from benign lipomas, as these are not found in normal fat tissue. Liposarcoma Variants Liposarcoma has several subtypes, each with unique morphological and behavioral characteristics: 1. Well-Differentiated Liposarcoma (Atypical Lipomatous Tumor): Most Common Variant: Resembles a lipoma macroscopically—yellow and well-defined. Microscopic View: Shows cells similar to normal fat cells but with atypical features like large, hyperchromic (dark-staining) nuclei and sometimes lipoblasts. It may look similar to normal fat tissue except for the presence of these atypical cells. Prognosis: Generally has a good prognosis and does not behave aggressively. 2. Myxoid Liposarcoma: Second Most Common Variant: Distinguished by its unique basophilic extracellular matrix (a gel-like substance) that appears bluish on microscopic slides. Microscopic Features: Contains a network of small, branching (anastomosing) capillaries and has a characteristic pinkish or blue tint. The basophilic extracellular matrix is key to recognizing this subtype. Behavior: Has intermediate behavior—it can be aggressive but is generally less malignant than pleomorphic liposarcoma and does not appear retroperitoneally. 3. Pleomorphic Liposarcoma: Rare and Aggressive Variant: Composed of highly atypical cells with irregular, large nuclei and many fat vacuoles. Microscopic Features: Shows a disorganized structure with immature adipocytes (fat cells) and poorly formed, large, and jagged nuclei. The presence of numerous lipoblasts is common. Behavior: This variant is highly aggressive, likely to metastasize, and has a poorer prognosis. Additional Information Prognosis and Behavior: Well-differentiated (atypical lipomatous tumors) have a better prognosis and are less likely to metastasize. Myxoid liposarcoma has an intermediate level of malignancy. Pleomorphic liposarcoma is highly aggressive with a tendency to metastasize. Understanding these subtypes is essential for diagnosis and treatment planning because each subtype has a different clinical behavior and prognosis. Fibro Tissue Tumors Nodular Fasciitis Type: A type of reactive proliferation (non-cancerous growth that resembles a tumor). Common in: Young adults, though it can appear at any age. Location: Often found in the flexor muscles (usually the left side), between muscles and subcutaneous tissue. Association with Trauma: About 25% of cases have a history of prior injury to the area. Characteristics: Size: Small (typically under 5 cm) but grows quickly. Appearance: Macroscopically, it has somewhat defined borders, although it may spread slightly into surrounding tissues. Microscopic View: Shows a loose, myxoid (gel-like) matrix, sometimes with small cysts. Cells are densely packed, and there is visible mitosis, but nuclei are not hyperchromatic or pleomorphic, which differentiates it from sarcoma. Fibromatosis Fibromatosis is a benign fibroblastic tumor and is categorized into superficial and deep types. Superficial Fibromatosis Characteristics: Non-cancerous growths involving fibroblasts that are mostly seen in men. Types: Palmar Fibromatosis (Dupuytren's Contracture): Causes nodular thickening in the palmar fascia, resulting in the flexion of the 4th and 5th fingers. Plantar Fibromatosis: Affects the sole of the foot but does not cause contracture. Penile Fibromatosis (Peyronie's Disease): Causes a palpable mass on the dorsal or lateral side of the penis, sometimes narrowing the urethra. Deep Fibromatosis (Desmoid Tumor) Characteristics: Larger, infiltrative, benign but recurrent masses. Though non-metastatic, they are locally aggressive. Age Group: Commonly seen in people from adolescence to 30 years. Common Locations: Usually seen in the muscles of the anterior abdominal wall or proximal limbs. Associated Mutations: Linked to APC or beta-catenin mutations that increase WNT signaling; some cases are associated with familial adenomatous polyposis (FAP). Appearance: Usually white or gray, with unclear borders and either soft or hard consistency. They infiltrate surrounding structures like muscle, fat, and nerves. Microscopic View: Shows fascicles of fibroblasts in a dense collagen matrix. Fibroblasts have elongated nuclei, with collagen encircling them. Fibrosarcoma Type: A malignant type of fibrous tissue tumor. Location: Can arise from superficial or deep connective tissues, often seen in tendons. Growth: Grows slowly, with defined borders. Soft in consistency, and may show areas of necrosis and bleeding. Microscopic View: Low-Grade Type: Shows fibroblasts arranged in fascicles that intersect at acute angles, giving a fishbone-like appearance. Mitosis is rare. High-Grade Type: Cells are smaller, round, and don’t have a clear fascicular pattern. There is an increase in mitosis and necrosis. Fibrohistiocytic Tumors Fibrohistiocytic tumors are a group of tumors composed of fibroblasts (cells that create connective tissue) and histiocytes (macrophage-like cells that can sometimes contain fat). They are classified into benign and malignant types, with different characteristics and clinical behavior. --- Benign Fibrous Histiocytoma (Dermatofibroma) Also Known As: Dermatofibroma when in the skin. Location: Typically occurs just beneath the skin but can sometimes appear in deeper tissues. Clinical Features: Usually small (often less than 1 cm). Moves slightly when touched and has a well-defined border. Microscopic Features: Composed of multifaceted cells tightly packed together. Cells have low eosinophilic cytoplasm (staining pink on slides) and are compact. Shows a unique characteristic called collagen trapping where surrounding collagen fibers are "trapped" at the lesion's edge, serving as a diagnostic marker. --- Malignant Fibrous Histiocytoma (Undifferentiated Pleomorphic Sarcoma) Current Term: Known now as Undifferentiated Pleomorphic Sarcoma (UPS), as "malignant fibrous histiocytoma" is no longer commonly used. Naming Convention: Soft tissue tumors are often named based on the tissue they most resemble. For example: Lipoma is benign, and liposarcoma is its malignant counterpart. Tumors with poor differentiation (showing no clear resemblance to any specific tissue) were historically classified as malignant fibrous histiocytoma, but advances in molecular genetics have reclassified many based on identifiable tissue markers. Those that lack any specific tissue markers remain in the undifferentiated pleomorphic sarcoma category. --- Characteristics of Undifferentiated Pleomorphic Sarcoma (UPS) Location: Most often found in deep soft tissues, particularly of the thigh and retroperitoneum. Age Group: Commonly occurs in middle-aged and older adults. Genetic Makeup: Frequently aneuploid, meaning they have abnormal chromosome numbers or structures. Size and Appearance: These tumors are typically large, ranging from 10-20 cm in diameter. They create fleshy or arrow-shaped masses with a white/gray color. Necrosis (cell death) and bleeding are commonly observed within the tumor. --- Microscopic Features of UPS Cell Morphology: Contains large cells with highly variable and irregular nuclei. Nuclei are described as bizarre due to their abnormal and exaggerated appearance. Atypical mitoses (irregular cell divisions) are common and abundant. Differentiation: These tumors lack differentiation, meaning they do not show features of specific tissues such as nerve, fat, or fibrous tissue. Aggressiveness: Known for aggressive behavior with poor prognosis. Approximately 30-50% of cases have already metastasized by the time of diagnosis. --- Treatment and Prognosis Treatment Options: Surgery and chemotherapy are commonly used, but the effectiveness may vary. Prognosis: Generally poor due to high rates of metastasis and the aggressive nature of these tumors. Synovial Sarcoma Tumor Synovial sarcoma is a type of soft tissue sarcoma initially thought to originate from the synovium (lining of joints), as it was first found near the knee joint. However, it can actually appear in other parts of the body and has no direct connection with the synovium. --- General Characteristics Incidence: Accounts for 10% of all soft tissue tumors and is the fourth most common sarcoma. Age Group: Primarily seen in individuals between 20-40 years old. Location: Typically located near large joints like the knee and elbow but can also occur in other deep body locations. Macroscopic Features: The tumor has well-defined boundaries and may show areas of calcification. Microscopic Characteristics Synovial sarcoma has two key histological components, making its structure unique and critical for diagnosis: 1. Epithelial Component: Can form gland-like structures similar to epithelial tissues. 2. Sarcomatous Component: Composed of spindle-shaped cells that may be arranged in fascicles, resembling fibroblasts. Both components are typically present, though in some cases, only one component is found. When only one component (either epithelial or sarcomatous) is present, the tumor is termed a monomorphic variant. --- Diagnostic Challenges and Markers Monomorphic Variant: If a tumor has only one component, diagnosing it becomes challenging. The cytokeratin marker can assist in this situation. Cytokeratin Positivity: In synovial sarcoma, both the epithelial and sarcomatous components are positive for cytokeratin, which is unusual because cytokeratin is usually only seen in epithelial cells. This dual positivity is a key feature in diagnosing synovial sarcoma, especially when only one component is present. --- Summary Synovial sarcoma is notable for its unique combination of epithelial and sarcomatous elements, its frequent occurrence near major joints, and its need for specialized markers (like cytokeratin) for accurate diagnosis, particularly in cases with a monomorphic appearance. the tumors of skeletal muscle and smooth muscle: Skeletal Muscle Tumors Skeletal muscle tumors are rare and mostly malignant, with benign forms being uncommon. Tumors of skeletal muscle origin are primarily classified as rhabdomyomas (benign) and rhabdomyosarcomas (malignant), with the latter being much more common. Rhabdomyosarcoma Types Rhabdomyosarcoma, a malignant tumor of skeletal muscle, has three main morphological types: 1. Embryonal Rhabdomyosarcoma: Age and Location: Commonly seen in children, often affecting the head and neck area, retroperitoneum, bile ducts, and urogenital tracts. In the head and neck, it may involve the orbit, nasopharynx, oral cavity, and middle ear. Microscopic Features: Contains sheets of small, round cells with pericellular spaces (around blood vessels), creating areas with fewer cells. Botryoid Subtype: This subtype forms grape-like clusters, known as a botryoid lesion, under epithelial coverings in organs such as the nose, bladder, and vagina. Under the microscope, cells accumulate beneath the epithelium in a pattern known as cambium layer. This subtype has the best prognosis among rhabdomyosarcomas. 2. Alveolar Rhabdomyosarcoma: Age and Location: Typically occurs in older children and young adults (ages 10-25) and may be found in deeper tissues and organs. Microscopic Features: Characterized by a network of septa (thin partitions), with cells either free within the spaces or attached to the septa. Cells generally have round to oval nuclei, minimal cytoplasm, and occasionally appear multinucleated. Prognosis and Metastasis: It has a poorer prognosis than embryonal rhabdomyosarcoma and often spreads to the lungs, as well as other organs like lymph nodes. 3. Pleomorphic Rhabdomyosarcoma: Age and Location: Seen only in adults. Microscopic Features: Highly variable in cell shape and size with atypical, pleomorphic cells. Prognosis: Typically more aggressive with a high potential for metastasis and poor prognosis. --- Smooth Muscle Tumors Smooth muscle tumors arise from smooth muscle cells and are commonly known as leiomyomas (benign) and leiomyosarcomas (malignant). Leiomyoma (Benign Smooth Muscle Tumor) Most Common Location: Leiomyomas are most often found in the uterus but may also appear in the skin, nipples, scrotum, gastrointestinal tract, and other soft tissues. Types and Symptoms: Pilar Leiomyoma: Originates from the arrector pili muscles (small muscles attached to hair follicles) in the skin and may be multiple and painful. It can be associated with uterine and kidney leiomyomas. Soft Tissue Leiomyoma: Typically 1-2 cm in size and well-circumscribed, making surgical removal straightforward. They consist of smooth muscle fascicles with elongated, narrow nuclei, and show no mitosis or necrosis. Morphology: Smooth muscle fascicles with elongated, narrow nuclei. No mitosis or necrosis is seen, which distinguishes it from malignant types. Leiomyosarcoma (Malignant Smooth Muscle Tumor) Frequency: Accounts for 10-20% of soft tissue sarcomas and is more common in women. Associated Conditions: Linked with Epstein-Barr Virus (EBV) infection in immunocompromised individuals. Common Locations: Often found in the skin, deep soft tissues of organs, and blood vessels, particularly large vessels like the inferior vena cava. Retroperitoneal Leiomyosarcomas: These types can become very large, are aggressive, and have a poor prognosis. Macroscopic Features: Often large, firm masses with clear boundaries. Necrosis and bleeding areas are frequently present, indicative of their malignant nature. Microscopic Features: Composed of spindle-shaped cells with blunt, rounded ends, often forming fascicles. Cells exhibit hyperchromic (dark-staining) and atypical nuclei. Key differentiating features from leiomyomas are the presence of mitosis and necrosis, suggesting malignancy. ********************* Summary Skeletal Muscle Tumors: Primarily rhabdomyosarcomas, with embryonal, alveolar, and pleomorphic types. Benign rhabdomyomas are rare. Botryoid rhabdomyosarcoma (a subtype of embryonal) has a better prognosis. Smooth Muscle Tumors: Benign leiomyomas are common, especially in the uterus. Malignant leiomyosarcomas are aggressive, with a poor prognosis, often found in large blood vessels and deep tissues.