The pathology of the oral cavity includes not only soft- and hard-tissue diseases similar to other organs involving the mucous membrane and bone, but also diseases that form in teeth existing in jaw bones and salivary glands. The surface of the oral cavity is covered by mucous membranes, on which numerous appendages such as gustatory receptors and minor salivary glands exist. Most of the cases of malignant tumors (oral cancers) are squamous carcinoma originating from the stratified squamous epithelium that covers the oral mucous membrane. The annual number of deaths caused by oral cancers is 7,000 in Japan and is increasing yearly. Salivary glands are anatomically classified into the major salivary glands (e.g., parotid glands, submaxillary glands, and sublingual glands) and minor salivary glands (e.g., palatine glands and labial glands). There are various types of lesion that occur in the salivary glands, which are roughly classified into non-neoplastic lesions (e.g., inflammation, metaplasia/hyperplastic lesions, and cysts) and neoplastic lesions. In addition to ductal epithelial and acinar cells, myoepithelial and basal cells also exist in the salivary glands. Tissue images of salivary gland tumors are diverse because the proliferation and differentiation of cells occur at various rates along with the development of cancerous tumors. Cancerous tumors generally develop unilaterally. Most of the cases of bilateral swelling of salivary glands are caused by non-neoplastic lesions. However, malignant lymphoma, Warthin tumor, pleomorphic adenoma, and adenoid cystic carcinoma sometimes develop bilaterally. Approximately 80% of cases of salivary gland tumors develop in major salivary glands, especially in the parotid glands, most of which are benign. However, the frequency of malignant tumors is higher than that of benign tumors in the case of tumors that develop in minor salivary glands.

Esophageal nonneoplastic lesions are classified into those causing dysplasia, malformation, dysfunction, circulatory disorder, and inflammation. Among nonneoplastic lesions, those causing esophageal hiatus hernia, esophageal achalasia, and esophageal varix are particularly important. The mucous membrane of the lower esophagus of the patients with reflux esophagitis is damaged by the reflux of gastric contents and the stratified squamous epithelium continuously metamorphoses into a columnar mucosal epithelium called Barrett’s epithelium, from the site of an esophagogastric junction. Squamous carcinoma and adenocarcinoma are malignant epithelial tumors. In Japan, squamous carcinoma accounts for ≥90% of the cases of esophageal cancer. Most adenocarcinomas originate from Barrett’s epithelium. The stomach is a saclike organ located between the esophagus and the duodenum. The stomach temporarily stores and mixes ingested food, digests them with gastric juices, and secretes various hormones that promote digestion. Similar to other digestive tracts, the walls of the stomach consist of four layers: the mucous membrane, submucosa, gastric muscularis, and gastric serosa. Gastric ulcer refers to a partial defect and break of the inner surface of the stomach. Gastric erosion refers to the state in which the mucous membrane is damaged, but it does not reach the submucosa. Most cases of gastritis in Japan are caused by Helicobacter pylori infection. It was found that chronic persistent infection with H. pylori leads to chronic gastritis. Most of the gastric malignant epithelial tumors are carcinoma (adenocarcinoma). Malignant lymphoma and gastrointestinal stromal tumor are malignant nonepithelial tumors. The large intestine is divided into six sections: the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. The characteristics of the mucous membrane are similar throughout the large intestine from the cecum to the rectum. The muscularis mucosa is a characteristic structure of the large intestine. This layer regularly contracts to secrete mucus and excrete stool. There are two types of germ cell in the large intestine: absorptive epithelial cells and mucus-secreting cells. These types of germ cell form tubular glands or crypts, which reach the muscularis mucosa. Lesions of the large intestine include those causing Hirschsprung’s disease, a morphological and functional disorder; ischemic enteritis, a circulatory disorder; inflammation; and tumors (endothelial tumor, interstitial tumor, and malignant lymphoma).

The pancreas consists of the pancreatic duct epithelium (columnar epithelium), islets of Langerhans, and acinar cells. It relates to internal and external secretions. The pancreas frequently contains fat. Among pancreatic tumors, the frequency of pancreatic ductal carcinoma (adenocarcinoma) is the highest, followed by pancreatic neuroendocrine tumor forming in islets of Langerhans, and acinar cell tumor. Other pancreatic tumors include autoimmune (IgG4)-related tumors, solid pseudopapillary neoplasm, leiomyosarcoma, metastatic pancreatic cancer, and squamous carcinoma. Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) has been widely used for the diagnosis of pancreatic tumors. The definite diagnosis is made by staining techniques, such as rapid and simple May–Giemsa’s staining, Papanicolaou (Pap) staining, and hematoxylin and eosin (HE) staining of cell blocks, and immunohistochemical staining. Cytodiagnosis is mainly carried out for pancreatic tumors. HE staining of cell blocks and histopathological tissue examination by immunohistochemical staining are also carried out for some tissues. Therefore, full and detailed knowledge of cytological and histological characteristics of pancreatic tumors is indispensable for their precise diagnosis. It is important to acquire expertise to distinguish different types of pancreatic tumor from the results of various staining methods. Medical experts are required to understand the characteristics of pancreatic tumors and apply this knowledge to the precise identification of various types of pancreatic tumor.

The liver exists below the diaphragm and appears to cover the stomach. Four hepatic lobes constitute a liver that is supported by the falciform ligament of the liver extending from the diaphragm and the abdominal wall. The liver is the largest organ among digestive organs. The approximate weights of the liver of adult males and females are 1–1.3 and 1 kg, respectively. The liver consists of hepatic lobules, a portal region (Glisson’s capsule, a supporting tissue), and central veins. There are central veins at the center of hepatic lobules. A hepatic lobule consists of hepatic cells, endothelial cells, Kupffer cells, hepatic stellate cells, and sinusoidal pit cells. Dendritic cells exist in the portal region. The functions of the liver are diverse: metabolism of sugars, lipids, and proteins, production and secretion of bile, detoxication, metabolism of drugs, and retention of vitamins and iron. Approximately 600 mL of bile is produced by hepatic cells per day. The bile produced is secreted into the duodenal papilla through the intrahepatic bile duct, extrahepatic bile duct, gallbladder, and common hepatic duct. The bile is temporarily stored in the gallbladder and its flow is controlled by Oddi’s sphincter of the duodenal papilla as the muscular valve. When the duodenum is stimulated by food, it secretes cholecystokinin, which shrinks the gallbladder, leading to the relaxation of Oddi’s sphincter to discharge the bile into the duodenum. When the liver is infected with a hepatitis virus, hepatic cells may transform into tumor cells. It is necessary to understand the basic structure and functions of the liver because various diseases in addition to tumor may develop in the liver.

The upper respiratory tract generally refers to an airway consisting of the nasal cavities, paranasal sinuses, pharynx, larynx, and trachea. The paranasal sinuses that exist at an end of the respiratory region are divided into the frontal, sphenoidal, ethmoidal, and maxillary paranasal sinuses. Neoplastic diseases of nasal cavity and paranasal sinus regions include salivary gland-type tumors, olfactory neuroblastoma, maxillary cancer, and lymphoma. The main bronchus is repeatedly divided into smaller bronchi, which lead to terminal bronchioles and finally to bronchioles and pulmonary alveoli. Pulmonary diseases are classified into three types: circulatory failure, infectious and noninfectious pneumonia, and neoplastic lesions. Among pulmonary diseases, the frequency of infectious pneumonia is extremely high, which is one of the top causes of death and the main respiratory disease. Infectious pneumonia is caused by many types of pathogenic microorganism, such as bacteria, viruses, mycoplasmas, fungi, and protozoa. Commonly, special staining methods are effective in the diagnosis of infectious pneumonia. Adenocarcinoma is the most common histological type and accounts for ~60% of all pulmonary tumor cases. The number of female patients is high and adenocarcinoma frequently develops in the periphery of lungs. Squamous cell carcinoma accounts for ~30% of all pulmonary tumor cases. The number of male patients is high and squamous cell carcinoma develops mainly at the center of lungs; however, cases of squamous cell carcinoma developing in the periphery of lungs have been increasing in number. Small-cell and large-cell neuroendocrine carcinoma account for ~10% and ~3% of all pulmonary tumor cases, respectively. Morphologically, both tumors show neuroendocrine features and the use of neuroendocrine marker staining is recommended. The mediastinum is divided into the superior mediastinum and inferior mediastinum. The inferior mediastinum is further divided into three sites: the anterior mediastinum, middle mediastinum, and posterior mediastinum. The type of tumor that commonly develops in the mediastinum depends on the site.

The shape and size of the heart are similar to those of a person’s fist. Its weight is about 300 g. The heart is located beneath the mediastinum and between the right and left lungs, and it is surrounded by the pericardium. The distal portion of the cardiac apex is located above the diaphragm and directed slightly leftward and downward. The anterior part of the heart consists mostly of the right ventricle. The main function of the heart is to pump blood to the entire body through the pulmonary circulation and the systemic circulation. The right side of the heart is responsible for the pulmonary circulation. Venous blood that returns from the entire body through veins enters the right side of the heart through the superior vena cava and inferior vena cava and is pumped to the pulmonary trunk. After carbon dioxide is removed and oxygen is delivered to red blood cells during gas exchange in pulmonary alveoli, blood returns to the left side of the heart through pulmonary veins. In the systemic circulation, the blood that has returned to the left side of the heart is distributed to all body tissues through the main arteries. After it is used in each tissue, it returns as venous blood to the right atrium. The amount of blood pumped by the heart per day is said to be more than 5,000 L. The blood pumped by the heart is circulated through the vascular system, which is divided into the arterial and venous systems. When the heart beats, blood flows through the main arteries and arterioles to reach the capillary bed of tissues. Then, blood flows through capillaries, venules, veins, and the vena cava to return to the heart. The tissues of blood vessels (except capillaries) consist of three layers: the tunica intima, tunica media, and tunica adventitia. However, the proportion of each layer differs between arteries and veins. Because cardiovascular diseases include all kinds of diseases such as inflammation, degeneration, circulatory disturbance, and tumors in the cardiovascular system, it is important to understand the pathology of these diseases.

Lymphoid tissues, such as lymph nodes, lymphatic tissue, and lymph follicles, are distributed in various parts of the body and function in immunity. Structurally, a lymph node is enclosed in a capsule and has afferent and efferent lymphatic vessels. A lymph node consists of a lymph node parenchyma and lymph sinuses. Lymphatic tissues are not enclosed in a capsule, unlike the lymph nodes. Lymphatic tissues do not have afferent and efferent lymphatic vessels and lymph sinuses. Lymphatic tissues correspond to the tonsils, bronchus-associated lymphoid tissues (BALTs), gut-associated lymphoid tissues (GALTs) such as those in Peyer’s patches, and the white pulp of the spleen. Lymph follicles are formed according to the states of systemic organs and tissues. Other lymphatic tissues include those in the thymus gland and bone marrow, which are responsible for the supply of lymphoid stem cells constituting the lymphoid tissues and the differentiation of immature lymphocytes. Recently, BALTs and GALTs have been recognized as mucosa-associated lymphoid tissues (MALTs) including those in the mucous membranes of other regions. The main diseases of lymphoid tissues include systemic changes induced by immunoreactions and malignant lymphoma. Hematogenesis begins in the yolk sac, liver, and spleen from an early stage of embryogenesis. At around the fourth month of intrauterine life, hematogenesis begins in the bone marrow, which continues after birth. Homogenesis occurs in all bone types at birth; however, homogenesis in appendicular bones ends by the first half of adult life. After that, the site of homogenesis moves to mainly the pelvis and spine. The bone marrow is divided into the fat-cell rich yellow bone marrow and red bone marrow. Nutrition is supplied to the bone marrow through the principal artery running through the bone cortex, which leads to telangions and collected again in the central vein for excretion. The main diseases of hematopoietic organs include anemia and leukemia.

Organs of the urinary system include the kidneys, urinary tract, urinary bladder, and urethra. Urinary organs filter blood that circulates throughout the body and serve as the pathway for metabolic wastes to be removed from the body through urination. The anatomical structures (size and position) of the organs in the lower part of the urinary system differ between men and women. Renal diseases include glomerular nephritis, nephrosclerosis, nephrotic syndrome, pyelonephritis, and renal cancer. Some renal diseases have symptoms of systemic diseases, such as diabetes and collagen disease. Diseases of the urinary tract include inflammatory diseases, such as cystitis and prostatitis, and malignant tumor. The number of cases of urinary tract epithelial tumor is high in terms of the tissue type of cancer. The urinary tract epithelial cells undergo metamorphosis resulting from inflammation and reactive swelling of the nucleus. Tumor lesions exhibit adluminal papillary growth and infiltrative growth piercing a basal lamina.

Typical endocrine organs include the hypophysis, thyroid glands, accessory thyroid glands, parathyroid glands, adrenal glands, the isles of Langerhans in the pancreas, ovaries, testes, and pineal body. In general, endocrine organs secrete various biological transmitters, which are delivered to remote target organs through blood vessels, to regulate growth, autonomic functions, and the internal environment by their binding with receptors and thus support life. Some diseases originating from endocrine organs indicate hormone excess, hormone deficiency, or hormone resistance. Specific symptoms, such as hyperreactivity and hypofunction, develop depending on the mechanism of hormone action. The causes of endocrine system disorders include autoimmune abnormalities, tumors, infection/inflammation, oxygen absorption insufficiency, and abnormal receptor activity. In addition, multiple endocrine neoplasia (MEN) causes multiple adenomas, hyperplasia, or carcinomas in endocrine glands, which are classified into MEN type I (Wermer syndrome), MEN type IIA (Sipple syndrome), and MEN type IIB. Autoimmune multiple endocrine syndromes, which comprise several autoimmune diseases and endocrine diseases, sometimes develop.

Female genital organs include the uterus, vagina, fallopian tubes, and ovaries. They are involved in the secretion of female hormones, production of eggs, and pregnancy. Tissues and cells in female genital organs vary in appearance depending on the age owing to the effects of menstruation, childbirth, and menopause. Female genital diseases are classified into benign (vaginitis, hysteroptosis, prolapse of uterus, uterine fibroid, and endometriosis), malignant (uterine cervical cancer, uterine body cancer, and ovarian cancer), and functional disorders (menstrual disorders, functional genital bleeding, climacteric disorder, and infertility).

Locomotorium includes bones (anatomical skeleton), arthroses (for mobile connections between bones), skeletal muscles (for connections to several bones via arthroses to move bones), and nerves (for impulse transmission). In this article, diseases of the locomotorium including soft tissues are discussed. Bones are divided into long bones, short bones, and plane bones on the basis of their shape. An epiphyseal region, the end portion of diaphysis, and a diaphyseal region exist from both expanded ends to the center of a long bone. A hard compact bone and a spongy cancellous bone exist at the periphery and the center of the cross section of a bone, respectively. The surface of a bone that is in contact with an arthrosis is covered with cartilage. Skeletal muscles are connected to periostea via tendons. Around the tissues mentioned above, collagenous fibers, fat tissues, and blood vessels exist locally. Bone diseases include inflammatory diseases, rachitic syndrome, osteoporosis, and bone fracture. Benign tumors originating from bones include osteochondroma. Malignant tumors originating from bones include osteosarcoma, chondrosarcoma, and giant cell tumor. In addition, there are metastatic bone tumors. In arthroses, rheumatoid arthritis suspected to be caused by autoimmune mechanism disorder, gout caused by purine metabolism disorder, and arthrosis deformans caused by aging can develop. Benign tumors originating from soft tissues include lipoma, leiomyoma, fibroma, and neurilemmoma. Malignant tumors originating from soft tissues include liposarcoma, rhabdomyosarcoma, leiomyosarcoma, and fibrosarcoma. In the diagnosis of these diseases, not only the clarification of the shapes of cells and tissues but also immunohistological and genetic analyses are necessary because the determination of disease-originating cells leads to the determination of the histologic type.

The skin consists of three layers, the epidermis, dermis, and subcutaneous tissue layers. The epidermis consists of a stratified squamous epithelium. The dermis consists of a papillary layer and a compact layer mainly consisting of collagenous fibers and elastic fibers, respectively. The subcutaneous tissue consists of adipose tissues. Various types of disease develop in the skin because it consists of various components from which a disease arises, for example, eczema (erythema and blister) and tumors originating from the stratified squamous epithelium and melanin-producing cells (melanocytes), other types of tumor originating from mesenchymal components such as connective tissues, and infectious skin diseases caused by pathogenic microorganisms. Autoimmune diseases causing bullosis in eczema include pemphigus vulgaris and bullous pemphigoid, in which epidermal intercellular substances and basement membranes are the antigen, respectively. Benign tumors originating from squamous cells include seborrheic keratosis and atheroma. Malignant tumors originating from squamous cells include squamous cell carcinoma (spinocellular carcinoma), basal cell carcinoma, and Bowen disease. Benign tumors originating from melanocytes include pigmented nevus and blue nevus. Malignant tumors originating from melanocytes include malignant melanoma. Mesenchymal tumors include benign lipoma and fibroma, as well as various types of malignant sarcoma. In addition to the diseases listed above, tumors originating from hair follicles, sebaceous glands, sweat glands, and vessels include extramammary Paget’s disease, sebaceous gland carcinoma, and sweat gland carcinoma. Tumors originating from hematopoietic cells include cutaneous malignant lymphoma. Infectious skin diseases are caused by viruses, bacterium, and fungi.

Nervous system diseases are a group of diseases that affect the central nervous system (brain and spinal cord), peripheral nerves, and muscles, including demyelinating diseases, degenerative diseases, cerebrovascular disorders, cerebral injuries, brain tumors, congenital neurological diseases, and nerve and muscle diseases. Many of these diseases are intractable and progressive, with their causes unknown and no effective treatments available. Recently, studies on the pathogenesis at gene and protein levels have progressed considerably. For example, the genes responsible for some familial neurodegenerative diseases have been identified. Accordingly, the importance of histopathological diagnosis has been growing. Guillain-Barre syndrome, which is characterized by the degradation of the myelin sheath, is a typical demyelinating disease of peripheral nerves. Neurodegenerative diseases include Parkinson’s disease, Alzheimer’s disease, spinocerebellar degeneration, and amyotrophic lateral sclerosis. Brain tumors develop in the skull (cerebrum, cerebellum, brainstem, dura mater, arachnoid membrane, blood vessels, pituitary gland, and 12 pairs of cranial nerves connected to the left and right hemispheres). Brain tumors are classified into primary brain tumors, which basically originate in the brain tissue, and metastatic brain tumors, which originate in other organs and spread to the brain. Primary brain tumors are further classified into benign and malignant brain tumors. Different from other cancers, there is no tumor, nodes, and metastases (TNM) classification or staging system for brain tumors. Brain tumors are classified according to their grade of malignancy. Astrocytoma, meningioma, schwannoma, and pituitary adenoma are classified as benign brain tumors. However, astrocytoma and meningioma may undergo malignant transformation. Pilocytic astrocytoma, oligodendroglial tumor, glioblastoma, and medulloblastoma are classified as malignant brain tumors. Glioblastoma and medulloblastoma are classified as grade IV brain tumors. Metastatic brain tumors commonly originate from lung cancer, breast cancer, prostate cancer, and lymphoma.

The prostate, seminal vesicles, penis, and testes are collectively called the male genital organs. Genital diseases include malformation and inflammation of any of these organs, as well as prostatic hyperplasia, prostatic carcinoma, and testicular tumors. Prostatic hyperplasia is a benign disease affecting most males as they age. Prostatic carcinoma manifests with very different pathological conditions depending on the stage of this disease. Testicular tumors, which are often found in young males, are broadly classified into germ cell tumors and sex cord/stromal tumors.