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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
The early lesions are usually asymptomatic. The patients presenting with an advanced stage of the disease comprises around 66-77% of the cases.
The most important signs include a lump in the neck when palpated and weight loss.
People may also present with fatigue as a symptom.
The primary tumor does not have readily discernible signs or symptoms as they grow within the tonsillar capsule. It is difficult to notice anything suspicious on examination of the tonsil other than slight enlargement or the development of firmness around the area.
The carcinoma may occur in one or more sites deep within the tonsillar crypts. It may be accompanied by the enlargement of the tonsil. The affected tonsil grows into the oropharyngeal space making it noticeable by the patient in the form of a neck mass mostly in the jugulodiagastric region.
As the tonsils consist of a rich network of lymphatics, the carcinoma may metastasise to the neck lymph nodes which many are cystic.
Extension of tumor to skull or mediastinum can occur.
The additional symptoms include a painful throat, dysphagia, otalgia (due to cranial nerve involvement), foreign body sensation, bleeding, fixation of tongue (infiltration of deep muscles) and trismus (if the pterygoid muscle is involved in the parapharyngeal space).
On the other hand, the tumor may also present as a deep red or white fungating wound growing outwards, breaking the skin surface with a central ulceration. This wound-like ulcer fails to heal (non-healing) leading to bleeding and throat pain and other associated symptoms.
During biopsy, the lesion may show three signs: Gritty texture, Firmness and cystification owing to keratinization, fribrosis and necrosis respectively.
Cervical lymphydenopathy may be present.
Carcinoma of the tonsil is a type of squamous cell carcinoma. The tonsil is the most common site of squamous cell carcinoma in the oropharynx. The tumors frequently present at advanced stages, and around 70% of patients present with metastasis to the cervical lymph nodes.
The most common site for the incidence of the tumor is: the lateral wall of oropharynx 45%; base of the tongue 40%; posterior wall 10% and soft palate 5%. The most reported complaints include sore throat, otalgia or dysphagia. Some patients may complain of feeling the presence of a lump in the throat. Approximately 20% patients present with a node in the neck as the only symptom.
Main risk factors of developing carcinoma tonsil include tobacco smoking and regular intake of high amount of alcohol. It has also been linked to a virus called Human Papilloma Virus (HPV type HPV16). Other risk factors include poor maintenance of oral hygiene, a genetic predisposition leading to inclination towards development of throat cancer, immunocompromised states (such as post solid-organ transplant), and chronic exposure to agents such as asbestos and perchloroethylene in certain occupations, radiation therapy and dietary factors.
Ninety percent of cases of head and neck cancer (cancer of the mouth, nasal cavity, nasopharynx, throat and associated structures) are due to squamous cell carcinoma.
Esophageal cancer may be due to either squamous cell carcinoma (ESCC) or adenocarcinoma (EAC). SCCs tend to occur closer to the mouth, while adenocarcinomas occur closer to the stomach. Dysphagia (difficulty swallowing, solids worse than liquids) and painful swallowing are common initial symptoms. If the disease is localized, surgical removal of the affected esophagus may offer the possibility of a cure. If the disease has spread, chemotherapy and radiotherapy are commonly used.
Signet ring cell carcinoma (SRCC) is a rare form of highly malignant adenocarcinoma that produces mucin. It is an epithelial malignancy characterized by the histologic appearance of signet ring cells.
Primary SRCC tumors are most often found in the glandular cells of the stomach (SRCC originates in the stomach in 90 percent of patients), and less frequently in the breast, gallbladder, urinary bladder, and pancreas. SRCCs do not normally form in the lungs, though a few incidences have been reported.
Among colorectal cancers, the prevalence of SRCC is less than one percent. Though incidence and mortality of gastric cancer has declined in many countries over the past 50 years, there has been an increase in occurrences of gastric SRCC-type cancers.
SRCC tumors grow in characteristic sheets, which makes diagnosis using standard imaging techniques, like CT and PET scans, less effective.
Lobular carcinoma "in situ" (LCIS) is a condition caused by unusual cells in the lobules of the breast.
Many do not consider it cancer, but it can indicate an increased risk of future cancer. The national database registrars, however, consider it a malignancy.
Unlike ductal carcinoma "in situ" (DCIS), LCIS is not associated with calcification, and is typically an incidental finding in a biopsy performed for another reason. LCIS only accounts for about 15% of the "in situ" (ductal or lobular) breast cancers.
In its early stages, it can go unnoticed. It can be painless with slight physical changes. But the precursor tissue changes, can be noticed by the doctors.
Early stage symptoms can include persistent red or white patches, a non-healing ulcer, progressive swelling or enlargement, unusual surface changes, sudden tooth mobility without apparent cause, unusual oral bleeding or epitaxis and prolonged hoarseness.
Late stage symptoms can include an indurated area, paresthesia or dysesthesia of the tongue or lips, airway obstruction, chronic serous otitis media, otalgia, trismus, dysphagia, cervical lymphadenopathy, persistent pain or referred pain and altered vision.
Krukenberg tumors often come to the attention when they cause abdominal or pelvic pain, bloating, ascites, or pain during sexual intercourse. Krukenberg tumors can occasionally provoke a reaction of the ovarian stroma which leads to hormone production, that results in vaginal bleeding, a change in menstrual habits, or hirsutism, or occasionally virilization as a main symptom.
All these symptoms are non-specific and can also arise with a range of problems other than cancer, and a diagnosis can only be made following confirmatory investigations such as computed tomography (CT) scans, laparotomy and/or a biopsy of the ovary.
Oral cancer, also known as mouth cancer, is a type of head and neck cancer and is any cancerous tissue growth located in the oral cavity.
It may arise as a primary lesion originating in any of the tissues in the mouth, by metastasis from a distant site of origin, or by extension from a neighboring anatomic structure, such as the nasal cavity. Alternatively, the oral cancers may originate in any of the tissues of the mouth, and may be of varied histologic types: teratoma, adenocarcinoma derived from a major or minor salivary gland, lymphoma from tonsillar or other lymphoid tissue, or melanoma from the pigment-producing cells of the oral mucosa. There are several types of oral cancers, but around 90% are squamous cell carcinomas, originating in the tissues that line the mouth and lips. Oral or mouth cancer most commonly involves the tongue. It may also occur on the floor of the mouth, cheek lining, gingiva (gums), lips, or palate (roof of the mouth). Most oral cancers look very similar under the microscope and are called squamous cell carcinoma, but less commonly other types of oral cancer occur, such as Kaposi's sarcoma.
In 2013 oral cancer resulted in 135,000 deaths up from 84,000 deaths in 1990. Five-year survival rates in the United States are 63%.
Like other cancers arising in the head and neck region, HPV+OPC may be an asymptomatic incidental finding of an abnormality in the mouth, by the patient or a health professional, present with local symptoms such as difficulties with speech, swallowing, and breathing as well as pain and infection, or as a swelling in the neck if the cancer has spread to lymph nodes there. These may be accompanied by more general symptoms such as loss of appetite, weight loss and weakness.
Primary signet ring cell carcinoma of the colon and rectum (PSRCCR) is rare, with a reported incidence of less than 1 percent. It has a poor prognosis because symptoms often develop late and it is usually diagnosed at an advanced stage. Five-year survival rates in previous studies ranged from nine to 30 percent. Average survival was between 20 and 45 months. It tends to affect younger adults with higher likelihood of lymphovascular invasion. It is worth noting that the overall survival rate of patients with SRCC was significantly poorer than that of patients with mucinous or poorly differentiated adenocarcinoma.
In advanced gastric cancers, the prognosis for patients with the SRCCs was significantly worse than for the other histological types, which can be explained by the finding that advanced SRCC gastric cancers have a larger tumor size, more lymph node metastasis, a deeper invasive depth and more Borrmann type 4 lesions than other types.
Like the cells of atypical lobular hyperplasia and invasive lobular carcinoma, the abnormal cells of LCIS consist of small cells with oval or round nuclei and small nucleoli detached from each other. Mucin-containing signet-ring cells are commonly seen. LCIS generally leaves the underlying architecture intact and recognisable as lobules. Estrogen and progesterone receptors are present and HER2/neu overexpression is absent in most cases of LCIS.
A Krukenberg tumor refers to a malignancy in the ovary that metastasized from a primary site, classically the gastrointestinal tract, although it can arise in other tissues such as the breast. Gastric adenocarcinoma, especially at the pylorus, is the most common source. Krukenberg tumors are often (over 80%) found in both ovaries, consistent with its metastatic nature.
Adenocarcinoma of the lung (pulmonary adenocarcinoma) is a common histological form of lung cancer that contains certain distinct malignant tissue architectural, cytological, or molecular features, including gland and/or duct formation and/or production of significant amounts of mucus.
Adenocarcinomas are highly heterogeneous tumors. Several major histological subtypes are currently recognized by the WHO and IASLC/ATS/ERS
- Non-invasive or minimally invasive adenocarcinoma
- Adenocarcinoma in situ of the lung (Bronchioalveolar carcinoma)
- Minimally invasive adenocarcinoma of the lung
- Invasive adenocarcinoma
- Acinar predominant adenocarcinoma
- Papillary predominant adenocarcinoma
- Micropapillary predominant adenocarcinoma
- Solid predominant adenocarcinoma
- Invasive mucinous adenocarcinoma
In as many as 80% of tumors that are extensively sampled, components of more than one of these subtypes will be recognized. In such cases, resected tumors should be classified by comprehensive histological subtyping. Using increments of 5% to describe the amount of each subtype present, the predominant subtype is used to classify the whole tumor. The predominant subtype is prognostic for survival after complete resection.
Signet ring and clear cell adenocarcinoma are no longer histological subtypes, but rather cytological features that can occur in tumour cells of multiple histological subtypes, most often solid adenocarcinoma.
Some variants are not clearly recognized by the WHO and IASLC/ATS/ERS classification:
- Enteric adenocarcinoma of the lung
- Cribriform adenocarcinoma of the lung
Human papillomavirus-positive oropharyngeal cancer (HPV+OPC) is a subtype of oropharyngeal squamous cell carcinomas (OSCC), associated with the human papillomavirus type 16 virus (HPV16). Historically, cancer of the throat oropharynx (throat) was associated with the use of alcohol and tobacco, but the majority of cases are now associated with the HPV virus. HPV+OPC differs in a number of respects from OPC not associated with HPV (HPV-OPC), and is considered a separate disease. HPV has long been associated with cancers in the anogenital region, but in 2007 it was also recognized as a cause of oropharyngeal cancer. HPV is common among healthy adults and is largely transmitted through sexual contact, but tobacco use increases the risk of cancer.
Detection of a tumour suppressor protein, known as p16, is commonly used to diagnose an HPV associated OPC. The extent of disease is described in the standard cancer staging system, using the AJCC TNM system, based on the T stage (size and extent of tumour), N stage (extent of involvement of regional lymph nodes) and M stage (whether there is spread of the disease outside the region or not), and combined into an overall stage from I–IV. In 2016, a separate staging system was developed for HPV+OPC, distinct from HPV-OPC.
The historical treatment of OPC was surgical, with an approach through the neck and splitting of the jaw bone, which resulted in a considerable risk of death. Later, radiotherapy with or without the addition of chemotherapy, provided a less invasive alternative, and the results in terms of treating the cancer, were comparable. Newer minimally invasive surgical techniques through the mouth have improved outcomes, and surgery is often followed by radiation and or chemotherapy in high risk cases. In the absence of high quality evidence, management decisions are often based on technical factors, likely functional loss and the persons preferences. Some HPV+OPC may first appear in lymph nodes in the neck, without an obvious source (cancer of unknown primary origin) but removal of tonsil tissue from the oropharynx will often show hidden disease. The presence of HPV in the tumour is associated with a better response to treatment and a better outcome, independent of the treatment methods used and a nearly 60% reduced risk of dying from the cancer. Most recurrence occurs locally and within the first year after treatment. The use of tobacco decreases the chances of survival. While most head and neck cancer has been declining with reduced smoking rates, HPV+OPC has been increasing. Compared to HPV-OPC patients, HPV+OPC patients tend to be younger, have a higher socioeconomic status and are less likely to smoke. In addition they tend to have smaller tumours, but are more likely to have involvement of the cervical lymph nodes. In the United States and other countries, the number of cases of oropharyngeal cancer has been increasing steadily, with the incidence of HPV+OPC increasing faster than the decline in HPV-OPC. The increase is seen particularly in young men in developed countries, and HPV+OPC now accounts for the majority of all OPC cases.
Attempts are being made to reduce the incidence of HPV+OPC by introducing vaccination that includes HPV types 16 and 18, found in 95% of these cancers, prior to exposure to the virus. Early data suggest a reduction in infection rates.
In urologic pathology, high-grade prostatic intraepithelial neoplasia, abbreviated HGPIN, is an abnormality of prostatic glands and believed to precede the development of prostate adenocarcinoma (the most common form of prostate cancer).
It may be referred to simply as prostatic intraepithelial neoplasia (abbreviated as PIN). It is considered to be a pre-malignancy, or carcinoma in situ, of the prostatic glands.
HGPIN in isolation is asymptomatic. It is typically discovered in prostate biopsies taken to rule-out prostate cancer and very frequently seen in prostates removed for prostate cancer.
Signs and symptoms of pseudomyxoma peritonei may include abdominal or pelvic pain and/or bloating, distension, digestive disorders, weight changes, increased girth, and infertility.
Large cell lung carcinoma with rhabdoid phenotype (LCLC-RP) is a rare histological form of lung cancer, currently classified as a variant of large cell lung carcinoma (LCLC). In order for a LCLC to be subclassified as the phenotype variant, at least 10% of the malignant tumor cells must contain distinctive structures composed of tangled intermediate filaments that displace the cell nucleus outward toward the cell membrane. The whorled eosinophilic inclusions in LCLC-RP cells give it a microscopic resemblance to malignant cells found in rhabdomyosarcoma (RMS), a rare neoplasm arising from transformed skeletal muscle. Despite their microscopic similarities, LCLC-RP is not associated with rhabdomyosarcoma.
Although rhabdoid variants of LCLC are sometimes referred to as "rhabdoid carcinomas", this particular term should be reserved for examples of "pure" rhabdoid neoplasms (i.e. those that do not contain cells containing other histological variants)
Pseudomyxoma peritonei (PMP) is a clinical condition caused by cancerous cells (mucinous adenocarcinoma) that produce abundant mucin or gelatinous ascites. The tumors cause fibrosis of tissues and impede digestion or organ function, and if left untreated, the tumors and mucin they produce will fill the abdominal cavity. This will result in compression of organs and will destroy the function of colon, small intestine, stomach, or other organs. Prognosis with treatment in many cases is optimistic, but the disease is lethal if untreated, with death by cachexia, bowel obstruction, or other types of complications.
This disease is most commonly caused by an appendiceal primary cancer (cancer of the appendix); mucinous tumors of the ovary have also been implicated, although in most cases ovarian involvement is favored to be a metastasis from an appendiceal or other gastrointestinal source. Disease is typically classified as low- or high-grade (with signet ring cells). When disease presents with low-grade histologic features the cancer rarely spreads through the lymphatic system or through the bloodstream.
The differential diagnosis of LCLC-RP includes secondary metastatic lesions, melignant melanoma of the lung with rhabdoid phenotype, mucinous adenocarcinomas (particularly those featuring signet-ring cells), rhabdomyosarcoma, epitheloid angiosarcoma, pleural mesothelioma, and plasmacytoma.
People over 20 years of age with Birt–Hogg–Dubé syndrome have an increased risk of developing slow-growing kidney tumors (chromophobe renal carcinoma and renal oncocytoma, respectively), kidney cysts, and possibly tumors in other organs and tissues. These tumors often occur in both kidneys and in multiple locations in each kidney. The average number of kidney tumors found in a person with BHD is 5.3, though up to 28 tumors have been found. Hybrid oncocytoma/chromophobe carcinoma, found in 50% of cases, is the most commonly found cancer, followed by chromophobe renal carcinoma, clear cell renal carcinoma, renal oncocytoma, and papillary renal cell carcinoma. People over 40 years old and men are more likely to develop kidney tumors, which are diagnosed at a median age of 48. Kidney cancer associated with BHD have been diagnosed in people at ages as young as 20.
In general, people with Birt–Hogg–Dubé syndrome are at roughly seven times the risk of kidney cancer compared to the unaffected population. Estimates of the incidence among people with the disease range from 14%–34%. Rarely, it is associated with clear cell renal cell carcinoma and papillary renal cell carcinoma. If it develops in someone with BHD, renal cell carcinoma occurs later in life and has a poor prognosis. Though the types of tumor typically associated with BHD are considered less aggressive, cases of advanced or metastatic kidney cancer have been observed in people with the syndrome. Both benign and cancerous tumors can reduce kidney function over time as they grow larger.
Diffuse stomach cancer is characterized by the presence of poorly differentiated tumor cells. Microscopic appearance is signet ring cell carcinoma, which is tumor cells with mucin droplet that displaces the nucleus to one side.
The appearance of the stomach is like a "leather bottle". It is characterized by a thick, rigid stomach wall caused by diffuse infiltration of tumor cells and extensive fibrosis.
Diarrhea may be a presenting symptom.
Birt–Hogg–Dubé syndrome affects the skin and increases the risk of tumors in the kidneys and lungs. The condition is characterized by multiple noncancerous dome-shaped tumors of the hair follicles (fibrofolliculomas), particularly on the face, neck, and—more rarely—the upper chest. The fibrofolliculomas are generally described as having an opaque white color or a yellowish tone and have a waxy, smooth texture. The tumors are always found on and around the nose and on and behind the outer ear. Typically, they first appear in a person's 20s or 30s, and are found in more than 80% of people with the syndrome above the age of 40. The tumors become larger and more numerous over time. Tumors differ between individuals: they may appear merged in plaques, look similar to a comedo with a plug of keratin, or include epidermoid cysts. A large number of tumors on the face can be associated with hyperseborrhea (abnormally elevated sebum production). The presence of fibrofolliculomas on a person's face can cause significant psychological distress.
Other tumors can include trichodiscomas (tumors of the hair disc, which may be identical to fibrofolliculomas), angiofibromas, and perifollicular fibromas. However, angiofibromas are more common in tuberous sclerosis. Along with the tumors, other skin conditions are seen in people with Birt–Hogg–Dubé syndrome. Approximately 40% of people or families with the disease have papules in their mouth, which can be located on the cheeks (buccal mucosa), tongue, gums, or lips. Either white or mucosa-colored, they are discrete, small, and soft and consist of fibrous tissue covered in thickened epithelium. Collagenomas of the skin are also found in some families. Many people with BHD have skin lesions that appear to be acrochordons (skin tags), but may instead be fibrofolliculomas. These lesions are usually found in the armpit, on the eyelids, and in folds of skin. Not all individuals develop the facial tumors; some families with the mutation that causes BHD develop only kidney tumors or spontaneous pneumothorax.