Carcinomatosis is defined as a condition characterized by development of multiple secondaries at multiple sites, after spread of carcinoma from a primary site, a condition far more serious than metastatic disease.
Presentation
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.
Entire Body System
- 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]
- Hodgkin Lymphoma
lymphoma C81.0 Nodular lymphocyte predominant Hodgkin lymphoma C81.00 …… unspecified site C81.01 …… lymph nodes of head, face, and neck C81.02 …… intrathoracic lymph nodes C81.03 …… intra-abdominal lymph nodes C81.04 …… lymph nodes of axilla and upper [icd10data.com]
lymphoma) elsewhere 1 peritonitis/sepsis smooth thickening and enhancement of the peritoneum, with stranding of the omentum and mesentery may be seen in intra-abdominal sepsis benign calcifications tend to be sheetlike, and nodal calcifications in these [radiopaedia.org]
Peritoneal lymphomatosis Most peritoneal lymphomatoses (PL) are non-Hodgkin lymphomas. Although primary lymphomas can develop on the peritoneal surface as a primary process, almost all PLs are secondary to a pre-existing lymphoma [3]. [jbsr.be]
Primary tumors The most frequent primary tumor in our study was lung cancer (35/77, 58.3%), followed by gastric cancer (10/77, 16.7%), breast cancer (6/77, 10%), melanoma (3/77, 5%) and non-hodgkin’s lymphoma (2/77, 3.3%). [nnjournal.net]
- Falling
I had a fall in 2014. I was down at our waterfront,… Submit an appointment request on our patient portal or contact our New Jersey and Pennsylvania campuses to speak with a patient advocate. [princetonbrainandspine.com]
THOMAS JE, FALLS E, VELASCO ME et al. - Diagnostic value of immunocytochemistry in leptomeningeal tumor dissemination- a report of two cases. Arch Pathol Lab Med 2.000; 124(5):759-61. [ Links ] 9. [scielo.br]
- Localized Edema
Bronchovascular bundle and alveolar septal thickening may be due to local edema, and the presence of nodules in some cases may suggest that tumor cells in lymphangitic carcinomatosis can grow locally [6-7]. [cureus.com]
Gastrointestinal
- 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]
Musculoskeletal
- Back Pain
A 65-year-old man was admitted with melena and low back pain at rest. X-ray examination showed rectal cancer with multiple bone metastases. Laboratory examination showed severe anemia and DIC. [ncbi.nlm.nih.gov]
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CASE REPORTS Case #1 A forty-two-year-old woman was diagnosed in August 2012 with T2N0M0 head of pancreas adenocarcinoma, after she presented with back pain and liver function test abnormalities. Her preoperative CA19-9 was elevated to 533 ng/mL. [pancreas.imedpub.com]
Cranial-nerve involvement: Impaired vision, diplopia, hearing loss, and sensory deficits, including vertigo; cranial-nerve palsies commonly involve CN III, IV, VI, VII, and VIII Spinal-root involvement: Nuchal rigidity and neck and back pain, or invasion [emedicine.medscape.com]
- Low Back Pain
A 65-year-old man was admitted with melena and low back pain at rest. X-ray examination showed rectal cancer with multiple bone metastases. Laboratory examination showed severe anemia and DIC. [ncbi.nlm.nih.gov]
Skin
- Ulcer
Put On By Cunning Two weeks after submucosal cancer cells injection in Group A, ulcerative gastric cancer with peritoneal carcinomatosis showed typical VX2 tumor pathology, with widespread intraperitoneal metastatic nodules, bloody ascites and perspicuous [wordnik.com]
Moreover, internal spreading germs and infection by way of ulcers rupturing when it comes to cancer of stomach or intestine etc. [healthoma.com]
In severe cases large blisters and ulceration can develop. The pain can be so severe that daily activities is limited. [oncolex.org]
Neurologic
- Seizure
These symptoms may be caused by low-level seizure activity, because the brain is affected by the cancer. [cbsnews.com]
This seizure lasted for half a minute and left the patient in a state of unconsciousness. Throughout the following day, seizures recurred several times and eventually the patient died in the evening. [ncbi.nlm.nih.gov]
MTX administration can cause acute arachnoiditis (nausea, vomiting, mental status changes), seizures, mucositis, or myelosuppression (avoidable with folic acid coadministration). [aboutcancer.com]
If left untreated, median survival is 4-6 weeks; if treated, median survival is 2-3 months. [28] Signs and symptoms Meningeal symptoms are the first manifestations in some patients (pain and seizures are the most common presenting complaints) and can [emedicine.medscape.com]
- Confusion
This patient demonstrates that solid tumors can present with leptomeningeal spread that often confuses the treating physician. Fungal or tuberculous meningitis can mimic LMC in the absence of neoplastic signs and negative CSF cytology. [ncbi.nlm.nih.gov]
Recent Posts May 22, 2019 May 15, 2019 May 08, 2019 June 15, 2017 Busting myths: 7 common chemotherapy misconceptions When you receive a cancer diagnosis, you may experience fear, anger, sadness and confusion. [cancercenter.com]
Presentation is very variable, and may be nonspecific (for example, headache or confusion) or with focal or multifocal neurological deficits (for example, cranial nerve palsies). [patient.info]
Nor is it to be confused with cancers that spread (metastasize) to the peritoneum. Peritoneal cancer starts in the peritoneum, and hence is called primary peritoneal cancer. [webmd.com]
- Vertigo
Clinical presentation of leptomeningeal carcinomatosis: Meningeal symptoms: Headaches, memory impairment, vomiting, vertigo, lethargy, general cognitive impairment. Hydrocephalus or ICP (increased intracranial pressure). [symptoma.com]
Her family reported headache, vomiting, diplopia and vertigo two months before. Medical examination found giddiness, inability to spontaneously open her eyes, mumbled response to questions; she located pain and had isocoric and normoreagent pupils. [scielo.isciii.es]
In a recent series of 60 patients with MC associated with breast cancer, 55% of patients had headache, 50% had cranial nerve paralysis, 23% had intracranial hypertension, 20% had vertigo and 12% had convulsions 13. [doi.org]
Cranial-nerve involvement: Impaired vision, diplopia, hearing loss, and sensory deficits, including vertigo; cranial-nerve palsies commonly involve CN III, IV, VI, VII, and VIII Spinal-root involvement: Nuchal rigidity and neck and back pain, or invasion [emedicine.medscape.com]
- Encephalopathy
Fixed focal neurologic deficits (eg, cranial-nerve palsies) generally do not improve, but encephalopathies can improve dramatically with treatment. [aboutcancer.com]
Metabolic changes affecting nervous tissue lead to seizures or encephalopathy. Formation of infarcts following blood vessel occlusion through their course through subarachnoid. [symptoma.com]
- Focal Neurological Deficit
Fixed focal neurologic deficits (eg, cranial-nerve palsies) generally do not improve, but encephalopathies can improve dramatically with treatment. [emedicine.medscape.com]
Workup
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.
Colonoscopy
- Polyps
Disease: Version SOC Term Classification Code Term Level 15.1 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) 10017758 Gastric cancer PT 15.1 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) [clinicaltrialsregister.eu]
The second patient underwent hysterectomy with bilateral salpingo-oophorectomy at the age of 64 due to an endometrial polyp. [omicsonline.org]
Treatment
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].
Prognosis
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].
Etiology
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.
Epidemiology
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.
Pathophysiology
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.
Prevention
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.
Summary
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.
Patient Information
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.
References
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