Carcinomatosis may present as a primary condition, without any precedent, or as a complication of a known malignancy. It may also exhibit a recurrence pattern. Its clinical presentation varies, depending on the location of carcinomatosis:

• Lungs: Shortness of breath, hemoptysis.
• Liver: Jaundice.
• Brain: Headaches, nausea, vomiting and neurological symptoms.
• Bones: Pain or pathological fractures.

The symptoms mentioned above are only some of the potential features of carcinomatosis. These are not always present and may be accompanied by further symptomatology.  

Isolated peritoneal metastases usually present with no symptoms. Peritoneal carcinomatosis itself may also be asymptomatic; however the majority of the patients exhibit some symptoms as the disease progresses, ranging from mild discomfort to severe pain. Symptoms include:

• Distension of the abdomen, due to cancer-induced ascites
• Nausea, vomiting
• Periodic pain
• Impaired bowel motility
• Bowel obstruction, usually observed in PC resulting from colorectal cancer.

Clinical presentation of leptomeningeal carcinomatosis:

• Meningeal symptoms: Headaches, memory impairment, vomiting, vertigo, lethargy, general cognitive impairment.
• Hydrocephalus or ICP (increased intracranial pressure).
• Palsies or radiculopathies, due to metastasis to the brain or spinal cord.
• Infarcts.

Upon presenting these symptoms, patients usually already have widespread cancer with poor prognosis and not many therapeutic options left. The diagnosis of multiple malignant masses in the CNS should always raise suspicion for LC.

• Pain

  The most common symptoms are chronic diarrhoea, weight loss, abdominal pain, arthritis and neurological abnormalities, which can be fatal. [ncbi.nlm.nih.gov]

  J Pain Symptom Manage 10.1016/j.jpainsymman.2016.05.032 [epub ahead of print on December 5, 2016] Google Scholar 4. [ascopubs.org]

  I had severe pain in my T12-L1 disc and vertebrae. It was severe over a period of time, to the point where it made me vomit, and ended up in an emergency room screaming. They contacted Dr. McLaughlin. [princetonbrainandspine.com]

  Pain control in terminal care and nausea and vomiting in palliative care might also be worthy of attention. Palliative care should not be perceived as a failure; it is highly demanding and rewarding. [disabled-world.com]

• Ascites

  Loculation of ascitic fluid is further a helpful feature. Ascites is seen in up to 70% of PC cases, although it is non-specific. [en.wikipedia.org]

  Ascites is variable and its presence alone may not imply peritoneal disease because ascites is often seen during therapy with tyrosine kinase inhibitors [ 8 ] (Figs. 2 and 3 ). [doi.org]

  […] mechanisms in ovarian cancer malignant ascites. [hindawi.com]

  ‘In ascites due to tuberculous peritonitis and peritoneal carcinomatosis, lymphocytes predominate.’ [en.oxforddictionaries.com]

  The CT findings observed in PL are similar to those of PC: diffusely thickened peritoneum, ascites, omental haziness, and multifocal nodules or masses in the peritoneal cavity [12, 13]. [jbsr.be]

• Surgical Procedure

  Peritoneal carcinomatosis: The dissemination of superficial peritoneal malignancy is most commonly seen in patients only subjected to surgical procedures. [symptoma.com]

  Laparatomy is a surgical procedure in which an incision is made in the abdomen to look at the amount and location of tumors in the abdominal cavity. Patients whose surgery reveals that the tumors cannot be removed are taken off study. [clinicaltrials.gov]

  There are several ways to treat this disease like; Chemotherapy called Heated Intraoperative Intraperitoneal Chemotherapy Administration Surgical procedure involving Peritonectomy procedures Dissect using electro-evaporative surgery with Intraperitoneal [healthoma.com]

  IPCH device At the end of each surgical procedure, an IPCH infusion ( Figure 1) was carried out under general anaesthesia and general hypothermia (32°C induced throughout the peritonectomy procedure, by cold wraps on both lower extremities, and an ice [ispub.com]

  The explorative laparotomy and intra-operative data evaluations were conducted by a surgical team of surgeon following a standard procedure and protocol. [clinicsinsurgery.com]

• Weight Loss

  This paper reports a case of a 57-year-old Brazilian woman with diarrhoea, vomiting, abdominal pain, appetite loss, intermittent fever, malaise, weight loss and malnutrition. [ncbi.nlm.nih.gov]

  Presenting symptoms of PLC are similar to those of interstitial lung disease and include dyspnea, cough, hemoptysis, fatigue, weight loss, and fever. [cureus.com]

  Physical findings: Clinical features of this disease include: • Ascites; • Abdominal swelling; • Constipation; • Gastrointestinal disorders; • Nausea; • Vomiting; • Anorexia; and • Unexplained weight loss. [secure.ssa.gov]

• Weakness

  He was admitted to our unit for intractable headache, nausea without emesis, anorexia, weakness, gait instability, delirium, syncope, and near syncope. [ncbi.nlm.nih.gov]

  In November 2014, I developed weakness in my left hand and severe pain radiating from the neck down through my shoulder and then to my fingertips. As a surgeon this had the… Derwyn H. Return to Performing My name is Derwyn. [princetonbrainandspine.com]

  […] cranial nerves such as optic nerve, auditory nerve, hypoglossal nerve, glossopharyngeal nerve also can be involved, which was similar with what already described in the literature.[ 9 ] In this study, there were 12 (15.6%) patients with bilateral limbs weakness [nnjournal.net]

  The latter can cause leg weakness, radiculopathy (usually lumbar, mimicking a herniated disk), reflex asymmetry or loss (most common, noted in 70% of patients), sphincter incontinence (less common), positive Babinski reflexes, paresthesias, and numbness [aboutcancer.com]

• Nausea

  He was admitted to our unit for intractable headache, nausea without emesis, anorexia, weakness, gait instability, delirium, syncope, and near syncope. [ncbi.nlm.nih.gov]

• Vomiting

  The clinical manifestation usually involves neurological symptoms, including dizziness, headache, vomiting, nausea, and hemiparesis, symptoms similar to those of meningitis or brain tumors. [ncbi.nlm.nih.gov]

  Brain: Headaches, nausea, vomiting and neurological symptoms. Bones: Pain or pathological fractures. The symptoms mentioned above are only some of the potential features of carcinomatosis. [symptoma.com]

  Most patients were admitted to hospital with increased intracranial pressure symptoms such as headache, nausea and vomit. [nnjournal.net]

  Pain control in terminal care and nausea and vomiting in palliative care might also be worthy of attention. Palliative care should not be perceived as a failure; it is highly demanding and rewarding. [disabled-world.com]

• Abdominal Pain

  The most common symptoms are chronic diarrhoea, weight loss, abdominal pain, arthritis and neurological abnormalities, which can be fatal. [ncbi.nlm.nih.gov]

  In March 2012, he had abdominal pain. The abdominal-pelvic ultrasound showed small amounts of ascites. The hepatitis B and C serologies were normal, liver function tests and blood counts were normal. [panafrican-med-journal.com]

  A 67-year-old man in relatively good health presented to the ED with abdominal pain, nausea and vomiting. [healio.com]

• Upper Abdominal Pain

  A 56-year-old man with complaint of upper abdominal pain exhibited adenocarcinoma upon histopathologic examination of biopsy specimens. At the end of adjuvant chemotherapy, the patient was affected by hearing loss. [ncbi.nlm.nih.gov]

• Irritability

  Besides, the meninges irritation is partly responsible for headache. [nnjournal.net]

  Sir, Diffuse or multifocal seeding of the leptomeninges by carcinoma, so-called meningeal carcinomatosis, often presents as simultaneous or rapidly sequential cranial neuropathy, with or without headache, altered mental status, or signs of meningeal irritation [nature.com]

  Headache, signs of meningeal irritation, abnormalities of the mental status, cranial nerve deficits, and seizures may indicate the leptomeningeal dissemination of a neoplasm primarily located outside the CNS3-5. [scielo.br]

  Painless hematuria is the most common presentation of TCC with other irritative voiding symptoms also often reported. [ijcasereportsandimages.com]

  Spinal-root involvement is caused by either meningeal irritation, presenting with nuchal rigidity and neck and back pain (rare), or invasion of the spinal roots. [aboutcancer.com]

• Neurologic Manifestation

  The paucity of neurologic manifestations can make diagnosis difficult, but the diversity of signals and symptoms as well as multifocal involvement, sometimes including cranial nerves or spinal roots, are both suggestive of MC5,7. [scielo.br]

The radiologic technique most widely used to assess patients suspected of peritoneal carcinomatosis is the CT scan; secondarily, MRI scans, ultrasound and, possibly, barium studies can also provide some information on the abdominal condition. The CT scan provides a reliable tool in order to detect PC and any other condition presenting with a similar symptomatology. The definitive diagnosis and characterization of the lesions observed is made possible through tissue biopsy, also conducted with the help of a CT scan, a procedure which facilitates the evaluation of the patient prior to surgery or any other treatment plan.

Surgery may be done of palliative purposes and 'debulking' of the malignancy prior to chemotherapy treatment. In cases of limited disease presenting with colorectal cancer and subsequent liver metastases, excision of the metastatic liver tumor has also seen some success. Patients with PC can benefit from radiotherapy if their tumor are symptomatic or massive in dimensions [14]; it can also be treated with intraperitoneal and/or intravenous chemotherapy, with both methods having increased the survival rate.

As far as leptomeningeal carcinomatosis is concerned, treatment may include intrathecal chemotherapy, intravenous chemotherapy, whole brain radiotherapy and radiotherapy to the spinal leptomeninges and it has also contributed to the improvement of survival rates in patients with metastases secondary to breast cancer [13]. A drug that has been evaluated as safe and effective in cases of HER-2 positive breast cancer patients is trastuzumab (intrathecal) [15].

Lymphatic carcinomatosis can on the other hand sometimes be rendered stable by means of chemotherapy.

Another method that is expected to play an important role in the treatment of disseminated, metastatic disease is the transcatheter arterial chemoembolization (TACE) [16]. It has proven effective, especially against neuroendocrine tumors and colorectal metastases. 

Palliative radiotherapy can often be implemented to reduce or eradicate pain caused by bone metastases. Palliative surgery, on the other hand, can be effective in cases of bowel obstruction due to carcinomatosis; however, it is accompanied by high mortality and morbidity when compared to the patient's remaining survival time [17] and it is therefore not frequently chosen. 

Cytoreduction surgery (CRS) and subsequent hyperthermic intraoperative peritoneal chemotherapy (HIPEC) has exhibited a certain efficacy in the treatment of peritoneal carcinomatosis secondary to colorectal cancer, but there is no data concerning other types of cancer [18].

Leptomeningeal carcinomatosis is an unusual complication of malignancy characterized by meningeal dissemination. It can affect both the spinal chord and the brain in around 5% of cancer patients. Median survival is 4 to 6 weeks without treatment and 2-3 months with appropriate treatment [9]; it is therefore deemed a terminal condition.

Peritoneal carcinomatosis is a manifestation of dissemination occurring from multiple malignancies, especially gastrointestinal tract carcinomas and ovarian cancer. Various cancer types and non-malignant conditions may present with findings that could indicate PC in radioimaging (CT) and it has been suggested that, due to the severity of the condition, the existence of peritoneal carcinomatosis should be evaluated first.

Conditions that present an image closely resembling that of PC are lymphomas, granulomatous infections such as tuberculosis, gastrointestinal stromal tumors (GIST) and primary peritoneal malignancies (mesotheliomas). Peritoneal carcinomatosis is a terminal stage condition.

Peritoneal carcinomatosis that presents without distant metastases is a disease restricted to a localized region of the body and requires aggressive regional treatment. Further evaluation is necessary after a CT scan, as the scan presents findings that are however nonspecific for PC; other cancer types as well as non-malignant peritoneal diseases may be seen as soft-tissue masses sometimes followed by ascites [11].

Pulmonary lymphangitic carcinomatosis is a dissemination of cancer cells to the lung, either from a primary lung cancer or from a distant location, via the bloodstream. The cancer cells then proceed to affect the lymphatics of the lung. Among pulmonary metastases, about 6%–8% of patients are affected by this form of carcinomatosis. As a result bronchovascular bundles and septa are thickened [12].

Peritoneal carcinomatosis: The dissemination of superficial peritoneal malignancy is most commonly seen in patients only subjected to surgical procedures. The mechanism is explained by the 'tumor cell entrapment" hypothesis which proposes the following potential pathways involving: 

• Serosal penetration by malignancy, leading to intraperitoneal tumor emboli. 
• Surgical trauma, which causes the release of malignant cells by venous blood flow.
• Transected lymphatics.
• Entrapment of tumor emboli on intraperitoneal locations, by fibrin, following trauma. During wound healing, factors which mediate growth actually promote the malignant cells, resulting in the state of carcinomatosis.

Lymphangitic carcinomatosis: It is the result of various primary cancers. The cancer type which most often leads to this condition is breast cancer and secondarily lung, colon, stomach, prostate and thyroid cancers. Malignant cells are hematogenously spread to the lungs and then further disseminate through the lymphatics, causing mass infiltration of the latter.  It may also be caused by a retrograde spread into lymphatics from the mediastinal and hilar lymph nodes. Lymphatic involvement includes the peripheral lymphatics coursing in the interlobular septa and beneath the pleura, and the central lymphatics coursing in the bronchovascular interstitium. Histological observations prove that tumors seen in the lymphatics and nearby interstitium are accompanied by edema and desmoplasia [5].

Leptomeningeal carcinomatosis: It is caused by the dissemination of malignant cells to the subarachnoid space. Cells that have found their way through the cerebrospinal fluid can, through its flow, be distributed throughout the entire central nervous system and cause multiple infiltrations. Cancer cells usually enter the CSF hematogenously or by direct extension. After the cerebrospinal fluid transports the malignant cells to various locations, the tumors that grow cause blockage of the CSF. The phenomena which accompany the blockage are:

• Local infiltration of the brain or spine, which leads to palsies or radiculopathies.
• Hydrocephalus/ elevated intracranial pressure.
• Metabolic changes affecting nervous tissue lead to seizures or encephalopathy.
• Formation of infarcts following blood vessel occlusion through their course through subarachnoid.

Studies show that 15% patients exhibit peritoneal carcinomatosis from the beginning and 35% of patients pass away because of PC reappearance. The administration of systemic chemotherapy helps to achieve a median survival period of 7–10 months longer in patients with metastases from gastric cancer, but patients presenting with additional PC do not equally benefit from it [6].

Literature data also show that nearly 25% of newly diagnosed cases of colorectal cancer are already affected by disseminated disease and the liver is primarily infiltrated in the majority of the cases. Given that liver metastases cases that are treated early progressed well, radiological screening for liver metastases is now conducted in patients who are diagnosed with colorectal cancer [7]. Another site of frequent concurrent metastases is the peritoneum.

Lymphangitic carcinomatosis is a term used to characterize the diffuse infiltration and blockage of pulmonary lymphatic channels caused by the malignancy. Multiple cancer types cause lymphangitic carcinomatosis, but the greater majority of them are adenocarcinomas [8]. Lymphangitic carcinomatosis belongs to a significant minority disease group, which causes interstitial rather than nodular pulmonary dissemination.

Last but not the least, leptomeningeal carcinomatosis is quite an uncommon complication of cancer, resulting in the dissemination to the meninges, namely the supportive membranes surrounding the central nervous system. Most of the times, this form of carcinomatosis is a sign of terminal stage and presented in 5% of cancer patients. If no intervention is attempted, the median survival period amounts to 4 to 6 weeks; if intervention is possible, survival extends to 2-3 months [9]. Cases diagnosed with leptomeningeal carcinomatosis, are approximately 1-8% of cancer patients.

Another interesting fact is that leptomeningeal carcinomatosis is observed post-mortem in the autopsical procedure in 19% of patients with cancer and neurologic symptoms, usually in those with metastases. The tumor type that most frequently spreads to the leptomeninges is adenocarcinoma, even though any systemic cancer type poses a potential threat. Dissemination of small-cell lung cancers to the leptomeninges affects 9-25% of cancer patients, 23% in melanomas and 5% in breast cancers. Since these cancer types do not share the same relative frequencies, leptomeningeal carcinomatosis is mostly exhibited by patients suffering from breast cancer.

Peritoneal carcinomatosis is a condition that troubles oncologists and gastrointestinal surgeons in treating patients. Though the disease is constrained within the peritoneal surface limits, it does not allow complete surgical excision and systemic chemotherapy to benefit the patient. It is therefore considered a terminal cancer stage and doctors often do not resort to any other type of treatment upon the PC diagnosis, other than supportive treatment.

Pathogenesis of peritoneal carcinomatosis is explained by three possible mechanisms:

• Cancer spreading to the peritoneal surface from a primary tumor source such as gastric cancer, colon cancer or pseudomyxoma peritonei.
• A primary peritoneal tumor like peritoneal mesothelioma or serous papillary peritoneal adenocarcinoma spreading to the whole peritoneum.
• Distinctly different origins of primary tumor and peritoneal infiltration such as low malignancy potential tumors of ovary or serous papillary peritoneal adenocarcinoma. The Goldie-Coldman model proposes that an initial population of tumor cells responding positively to chemotherapy undergoes mutation leading to resistance to chemotherapy [10].

On the other hand, lymphangitic carcinomatosis follows a more standard pathogenetic mechanism:

• Malignant cells spread into the lungs via the haematogenous route (with the exception of bronchogenic adenocarcinoma) and subsequently through lung lymphatics.
• Another possibility is the retrograde dissemination to the lymphatics from the mediastinal and hilar lymph nodes. Affected lymphatics include peripheral lymphatics coursing the interlobular septa and beneath the pleura, and the central lymphatics coursing through the bronchovascular interstitium.

Leptomeningeal carcinomatosis involves a specific clinical presentation caused by the obstruction of CSF fluid by malignancy. The subarachnoid space is infiltrated via CSF circulation, which has received malignant cells via the bloodstream (eg. leukemia) or by direct extension (brain cancer). Possible mechanisms for cancer dissemination to the leptomeninges include:

• Dissemination via the bloodstream to the choroid plexus and, subsequently, to the leptomeninges.
• Dissemination through the Batson plexus.
• Dissemination through the vessels of the leptomeninges.
• Retrograde spread through lymphatics and sheaths found in nerve-adjacent regions.
• Direct extension.

In order to optimize treatments for peritoneal carcinomatosis and prevent its recurrence, cytoreductive surgery and perioperative chemotherapy are considered a necessity that has to be conducted as early as possible in the course of the disease. Relapsing is further prevented by second-look surgery and hyperthermic intraperitoneal chemotherapy reserved for patients at high risk for recurrence. Hyperthermic intraperitoneal chemotherapy can also be used to treat or prevent carcinomatosis during primary colorectal cancer resection in some patients.

Peritoneal carcinomatosis as a complication of gastric cancer is a condition with a poor prognosis. It is generally deemed a terminal disease and mostly palliative therapy is attempted. Multimodal approaches have also been implemented, namely cytoreductive surgery (CRS) and peritonectomy with perioperative intraperitoneal chemotherapy (IPEC), including hyperthermic intraperitoneal chemotherapy (HIPEC) and/or early postoperative intraperitoneal chemotherapy (EPIC). Data is not extensive, but rather confined to few centers with experience in this field. Regarding patients with high risk gastric cancer, phase III trials and meta-analysis have shown that HIPEC is actually effective in the means of preventing peritoneal carcinomatosis [19].

Some patients that are treated early when the peritoneal  cancer is at a starting stage or patients that can be rendered cancer-free via surgical procedures, are expected to achieve a long-term survival period, without malignant manifestations. The method believed to be the most effective in such cases includes complete or extensive resection of tumors with subsequent administration of chemotherapy into the abdominal cavity. Chemotherapy is administered in full systemic doses [20] and includes mitomycin C and 5-fluorouracil for adenocarcinoma patients, whereas sarcoma patients receive cisplatin and doxorubicin.

This phenomenon is usually a result of a primary source of cancer having spread to multiple locations through various mechanisms. The condition is severer than metastasis or cancerous spreading to regional lymph nodes and it defines the presence of multiple secondary sites with malignant tumors. 

Initially used to define disseminated epithelial cancers or carcinomas, the term carcinomatosis has developed into a broader term, presently being used to describe any type of cancerous tumor that has spread. There are also various sub-types of carcinomatosis, characterized by limited dissemination:

• Peritoneal carcinomatosis: Usually a result of ovarian/colorectal cancer dissemination into the peritoneum. It has been proven to reduce overall survival in patients with liver metastases or dissemination outside the peritoneum from gastrointestinal cancer [1]. Peritoneal carcinomatosis is the final stage of primary peritoneal cancer (eg. mesothelioma) and also commonly occurs as a complication of progressed gynaecological cancers (appendicle tumor, ovarian tumor) and cancers of the digestive tract (colorectal or gastric cancer). Patients with peritoneal carcinomatosis of gastric origin have a poor prognosis with an average estimated survival of 1–3 months [3] [4].

• Pulmonary lymphangitic carcinomatosis: Most frequently observed when the primary cancerous source involves an adenocarcinoma. It indicates the dissemination of malignant cells through lung lymph nodes. It causes severe complications such as lymphatic channel blockage and a profound infiltration of the lungs. It results from many types of cancer, eg. breast and large intestine cancer.

• Leptomeningeal carcinomatosis: Cancerous cells spread through the cerebrospinal fluid (CSF), affecting the leptomeninges by direct spreading or via bloodstream. Any cancer type can result in leptomeningeal carcinomatosis but adenocarcinomas are most frequently involved. Leptomeningeal carinomatosis is not encountered frequently in clinical practice, as it constitutes a rarity, affecting only 5% of cancer patients. A variety of neurological symptoms and signs attributed to brain and/or spinal cord infiltration complete its clinical manifestation and it is diagnosed by assessing the clinical presentation, CSF cytology and imaging [2]. This complication of cancer is in the majority of cases an incurable condition, and patients receive combinations of therapies aimed at the amelioration of their symptoms and for palliative care.

Carcinomatosis is a condition involving extensive spread of cancer to multiple locations in the body. It is generally considered a terminal condition and generally difficult to cure. For these reasons, treatment is usually palliative: it involves surgery, chemotherapy and radiotherapy that aim to alleviate severe symptoms but is unable to completely cure a patient of the disease.

However, these is no general rule indicating that no patient can ever be rendered disease-free and have long survival. There have been patients, treated early and with malignancies that could be completely or almost completely resected, who have had successful results.

Patients diagnosed with peritoneal, leptomeningeal or lymphangitic carcinomatosis will need extensive evaluation from a team of doctors consisting of oncologists, surgeons and radiologists. Radioimaging helps to better assess a patients condition and strategically form a treatment plan. The outcome and success rates depend upon the disease stage, the location of the primary tumor (if any), co-existent conditions and other unknown factors. There have been some patients who have benefited a lot from combined treatment, whereas others only follow palliative treatment due to a very progressed condition.

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