Dr. Bailey.
Carolina Mñoz Codoceo.
A 70-year-old woman, born in Ecuador, came to the Emergency Department of the University Hospital "12 de Octubre" for increased abdominal perimeter, lower limb edema and constipation of 10 days duration.
He had a constitutional syndrome with weight loss of 10 kg in the last three months, which was not accompanied by abdominal pain, nausea, vomiting or fever.
There were no signs of gastrointestinal bleeding.
His personal history included type 2 diabetes mellitus, dyslipidemia and acute hepatitis in youth.
She had undergone cesarean section at 30 years of age, without having received blood transfusions.
His family history included a brother who died at age 50 due to liver cirrhosis of unknown etiology.
She continued on chronic treatment with metformin and denied toxic habits.
The patient had traveled to Spain from her country of origin 2 months before being admitted to our hospital.
Physical examination revealed blood pressure of 90/50 mmHg and temperature of 36.8oC.
The patient was conscious and oriented, impressed of severe disease and highlighted signs of malnutrition and lying down.
The patient had an abdomen with a semi-successful ascites (distaxis, mutable or positive color), lower limb edema, and decreased vesicular murmur on the right lung base.
There were no stigmata of chronic liver disease, abdominal pain and visceral enlargement.
The results of the peripheral blood analyses were as follows: Hb: 14.3 IU/dl; Hc 43%; VCM54abine, normal alkaline phosphatase, eosinophil count 36, 350,000/mm3; tumour lymphocytes 13,
The usual etiological study of chronic liver disease (viral, metabolic and autoimmune) was negative and thyroid hormone levels were within normal limits.
The ascitic fluid (AL) study showed the following results: leukocytes 3,700 (10% polymorphonuclear; 90% mononuclear BADH/ma; culture medium: 0%; glucose 72 mg/dl; protein 2,6 g/dl; albumin 1,190).
Immunohistochemistry of AL: absence of epithelial phenotype cells.
Malignant melanoma is characterized by: 93% of PMN, 1.2% of macrophages and 5% of lymphoid cells with very basophilic cytoplasm and immature nuclei with neutrophils.
Cellular immunophenotype of AL by multiparametric flow cytometry: scarce lymphoid population without monoclonality in population B; 1.7% of plasma-line immunophenotype cells with low expression of cytoplasmic (kappase chains).
Two AL cytologies were performed; the first was negative for malignant cells and the second was reported as "suspected malignancy".
Abdominal ultrasound showed liver cirrhosis with no signs of portal hypertension and grade 2/3 ascites that partially interfered with the examination.
Gynecologic ultrasound revealed "conglomerated masses in the pelvis compatible with carcinomatosis and ovarian tissue of aberrant aspect", confirming the existence of abundant ascites.
Transvaginal ultrasound showed an atrophic endometrium with no pathology and free fluid partitioned into the minor pelvis, without visualization of adnexal masses.
Chronic liver disease and massive ascites, without stenosis or dilation of the portal vein were found in non-pelvic CT scans.
There were varicose dilations in the mesenteric territory with heterogeneous involvement of the gastric fat, and possible relationship with implants or adenopathy at this level, as well as nonspecific thickening of the colon wall.
A Pathway was made up to 60 cm of anal margin, revealing a dilatable and peristaltic colon without other alterations.
Two weeks after admission to the Digestive Aparatus plant, the condition complicated with severe gastrointestinal bleeding.
A diagnostic procedure was performed.
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Differential diagnosis
Dr. Bailey.
Carolina Mñoz Codoceo.
In summary, this is a 70-year-old woman, His American, with abundant ascites, lower limb edema, constipation and a constitutional syndrome of three months duration.
The laboratory tests showed the following results: leukocytosis with neutrophilia, thrombocytosis, hypoalbuminemia, mild alteration of the hepatic profile (GOT and GGT), increased LDH and hyponatremia and hypernatremia.
In the study of AL leukocytes were increased, predominating the percentage of mononuclear cells, LDH levels were also above normal and in one of the cytologies malignant cells were identified.
The levels of CA-125 were high, both in peripheral blood and in the LA, and the difference between the value of albumin in serum and in the LA (GASLA: albuminS-gLA) liver mass was higher.
The main causes of ascites can be classified into two major groups according to GASLA.
This gradient results from subtracting the value of albumin in AT from that of this protein in serum and is an indirect and accurate indicator of portal pressure (1.2).
Thus, a high GASLA (≥ 1.1 g/dl) indicates the presence of PH with 97% certainty.
On the contrary, a low GASLA
(< 1.1 g/dl), allows guiding the etiological diagnosis of ascites to the group of causes without PH (Table I).
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In the clinical case that we discuss the calculation of the GASLA turned out to be ≥ 1.1 g/dl, a value that places us in the group of diseases that course with ascites secondary to PH, of which liver cirrhosis is more frequent.
Although the abdominal ultrasound and CT scan of our patient showed liver disease, this was not accompanied by indirect data of PH such as dilatation of the opportunistic axis and splenic enlargement.
In addition, the patient denied exposure to hepatotoxic substances, such as alcohol and some drugs, and the usual study of causes of chronic liver disease was negative, data that makes the diagnosis of cirrhosis unlikely.
However, with the information available, it is not possible to safely rule out steatohepatitis, especially in a diabetic patient (3).
The absence of hepatic encephalopathy and coagulopathy, in addition to the hepatic profile, and the subacute evolution of the condition, allow us to exclude acute liver failure among the possible diagnoses of the patient presented here.
The vascular causes of ascites with PH (Bordd-Chiari syndrome and veno-occlusive disease) and the lesions of the parenchyma may rule out liver metastases due to malignancy (hepatectomy).
Finally, the absence of heart disease and signs of heart failure, as well as normal thyroid hormones, exclude heart ascites and myxedematous in the patient we communicate (1.4).
Elevated GASLA and the presence of malignant cells in the LA of the case discussed are diagnostic of mixed ascites (1.2).
5% of ascites that course with GASLA ≥ 1.1 g/dl are called "mixed" and are characterized by having two etiologies, usually liver cirrhosis and other, such as peritoneal tuberculosis (4) or carcinomatosis.
The place of origin of our patient, the systemic clinic and the predominance of mononuclear leukocytes in the LA, forces us to consider the possibility of an underlying peritoneal tuberculosis (5).
In addition, tuberculosis can cause nonspecific elevation of CA-125, as in the present case (Table II).
Diagnosis of tuberculous peritonitis is often difficult because bacteriological results of AL or peritoneal tissue after laparoscopy are usually obtained late.
The quantification of interferon-gamma (IFN-g) and adenosine deaminase (ADA) in the LA are rapid and non-invasive methods that have demonstrated a sensitivity of 97% and a specificity of 94-97% (6).
The fact that this is a rare disease and the lack of data on tuberculosis infection in the LA of our patient (non-high AAD and IFN-g, AFB and culture in the setting of tuberculous colitis is unlikely to be negative),
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In our case, the finding of malignant cells in AL is a practically safe diagnosis of malignancy and flow cytometry can increase the probability of a positive diagnosis (7).
Malignant tumors are the cause of 10% ascites and malignant ascites is present in 15-50% of cancer patients (8).
Several mechanisms have been proposed for the production of tumor ascites (7.9): a) by peritoneal non-functioning due to intrahepatic bile duct adenocarcinomas (peritoneal obstructions); b) secondary to PH, compression or lymphatic invasion of the axis c).
In addition, there are studies showing that some cytokines such as IL-2, TNF-a or vascular endothelial growth factor may participate in the mechanism of formation of malignant ascites (7).
The cytology of the AL detects malignant ascites whenever the tumor cells are located next to the AL formation, that is, in peritoneal carcinomatosis and not in cases of liver metastasis, hepatocellular carcinoma or malignant lymphoma with obstruction.
On the other hand, cancer-related ascites may be associated with a high PMN count in the LA, presumably generating confusion because tumor cells attract neutrophils to the fluid, and this increase may result in confusion.
However, in malignant ascites lymphocytes generally predominate, as in the present case (7).
Malignant ascites is a manifestation of advanced tumoral disease and has a mean survival of two months, whatever its origin.
80% of cases of malignant ascites originate from ovarian, breast, endometrial, colon, stomach, pancreas and bronchi (8.9).
Ovarian tumors are the most common cause of malignant ascites, in 70% of cases they affect women 40-60 years of age and usually manifest as plenitude and abdominal pain (10, 11).
In the case presented here, the imaging obtained in the gynecologic ultrasound of pelvic conglomerated masses with a softened ovary, together with the serum increase of the marker CA-125, establish the suspicion of secondary ovarian carcinomatosis.
In addition, it is very common for these tumors to be accompanied by ascites and even hydrothorax (Meigs syndrome), as in our patient (5,11,12).
However, transvaginal ultrasound did not detect adnexal masses, and CAT scans showed lesions at this level.
Furthermore, it is known that the main utility of tumor markers, such as CA-125, is the follow-up of tumor processes and not their diagnosis and that this marker can also rise in a wide range of processes (Ta).
Gastric tumors are the second cause of malignant ascites (8).
They are more common in men and are usually diagnosed between 65 and 74 years of age, with a higher incidence in Japan, countries with a higher incidence of STI and former Soviet Union.
Gastric cancer is classified into two groups: adenocarcinoma and lymphoma (13).
Adenocarcinomas represent 90-90% of all stomach tumors and may be of two types: "intestinal or expansive", more differentiated, and "diffuse or endemic" 95% prognosis, with little differentiated, of a worse endemic character.
The "Krukenberg tumor" is included in this second group and is the term used to describe gastric adenocarcinoma that courses with ovarian metastases, usually bilateral, ascites and ovarian morphology (14) preserved.
In favor of this to be the diagnosis of the case discussed are the age and country of origin of the patient, the thickening of the gastric wall described in the CT scan, the initial malignant ascites CA-125, a high value.
Lymphomas account for 3-6% of gastric tumors and 95% of them are B-cell non-Hodgkin type (15).
In addition, 35-40% of these are B-cell gastric lymphomas of the marginal zone, which develop on "mucosal associated lymphoid tissue" (MALT lymphoma or primary gastric lymphoma).
The rest are diffuse large B-cell gastric lymphomas (16,17).
Primary gastric lymphomas usually appear in individuals around 60 years of age and with no difference in their distribution by sex (17,18).
They are related to a low socioeconomic level and specifically to Helicobacter pylori (Hp) infection, present in 98% of cases.
Its most frequent location is the antrum and in the initial stages they are usually asymptomatic although, with the progression of the tumor, abdominal pain, nausea, vomiting, anorexia, weight loss, bleeding, fever, sweating may appear.
The sensitivity of endoscopy with biopsy for the diagnosis of gastric lymphoma is 95%, since it allows its morphological study and perform immunophenotype analysis by immunohistochemistry and flow cytometry.
Endoscopic imaging of gastric lymphoma can simulate a polypoid mass, thickening of the folds or appear as ulcerative lesions, sometimes difficult to differentiate from adenocarcinoma (20).
Gastric MALT lymphoma can return with Hp eradication or progress to diffuse large B-cell lymphoma. Some mutations such as genetic factors that can intervene in this progression have been found (21).
The following diagnosis to consider among the causes of malignant ascites, in order of frequency, are colon neoplasms (1.2,7).
The age of the patient, the presence of changes in the intestinal rhythm, with a tendency to constipation, and the constitutional syndrome, together with the image in the CT of thickening of the colon wall this diagnostic suspicion justifies.
However, anemia and/or gastrointestinal abnormalities, normal tumor markers, and fundamentally atypical markers, do not show a mass in the absence of bleeding or tumor, this diagnosis with high probability discards.
On the other hand, the dilation and aperistalsis of the colon described in the CT could be justified by a tumoral compression and/or adhesions secondary to peritoneal tumor dissemination.
Finally, we must comment on the possibility that the condition can be explained by a neoplasm.
The study by flow cytometry of the AL introduces this diagnostic possibility because it allows a correct classification of hemopathies in 90% of cases when studying some physical aspects of the cell, the presence of cellular antigens supre (22).
The expansion of B cells with predominance of light chains kappa or lambda detected by this technique is typical of type B lymphoproliferative syndromes, such as multiple myeloma.
This type of tumors has a peak incidence between 50-70 years of age and usually manifests as a constitutional syndrome, often associated with renal failure (22.23).
However, cytometry did not allow establishing a specific diagnosis in the case discussed.
In addition, the absence of typical symptoms such as bone pain or anemic syndrome, normocytic-normochromic anemia, hypergammaglobulinemia and/or increased SGV diagnosis make it less likely.
On the other hand, gastrointestinal involvement and ascites are manifestations that rarely occur in this type of tumor, and we do not have this feature with increased urine electrophoresis in serum or urine or a biopsy for firm suspicion.
Dr. Martinez González (Pathological Anatomy).
Dr. Ulloa, could you describe the evolution of the patient and the procedure that led to her diagnosis?
Dr. Bailey.
Ulloa (digestive Apparatus Medicine).
The appearance of upper gastrointestinal bleeding secondary to urgent gastroscopy.
In this exploration, a body gastric mucosa with low distensibility and markedly thickened, edematous folds with multiple ulcerations was identified, taking biopsies.
The patient was then afflicted with hypovolemic shock complicated by acute renal failure, severe hyponatremia and hyperkalemia, and finally died due to multiple organ failure.
Dr. Bailey.
Carolina Mñoz Codoceo.
As already discussed, once the ovarian origin of ascites has been ruled out, the most likely cause to be considered is a stomach tumor.
In addition to the patient's age and origin, the image described in gastroscopy is compatible with diffuse scleroderma of the gastric wall or linitis plastica, associated with edematous folds and ulcerations.
These findings may correspond to gastric adenocarcinoma and lymphoma.
The absence of signet ring cells in the LA cytology and the presence of plasma cells in the AL would support the diagnosis of lymphoma.
The anatomopathological study of stomach biopsies performed in gastroscopy will probably offer the definitive diagnosis.
1.
Clinical diagnosis
Dr. Bailey.
Pérez Carreras (Medicina del Aparato Digestivo).
We believe the patient had an ovarian tumor with carcinomatous dissemination and malignant ascites.
However, considering the discordant information obtained in the different imaging tests, the severity of the condition and the possibility of obtaining a favorable response to chemotherapy, a gynecological laparoscopy was proposed and an evaluation was requested by the medical oncologists.
Although the patient was to undergo elective gastroscopy, the appearance of upper gastrointestinal bleeding was pending urgently.
1.
Clinical diagnosis of Dr. Bailey.
Minhoz Codoceo
Disseminated gastric adenocarcinoma with pelvic and peritoneal implants (Krukenberg tumor) vs. gastric lymphoma.
1.
Anatomopathological discussion
Dr. Bailey.
Garrido Ruiz.
Endoscopic biopsy was performed in several samples at the gastric body (4 fragments of tissue grouped measuring 0.8 x 0.8 x 0.3 cm).
From the microscopic point of view, we observed a fragment of gastric mucosa with common histological characteristics and several specimens showing extensive infiltrate by a neoformation of round cells, medium-sized vesicular nuclei with prominent lymphoid aspect.
Likewise, foci of gastric mucosa with focal but extensive infiltrates of small lymphocytes, with moderate atypia, arranged in aggregates and with images of lymphoepithelial lesion were observed.
With these histopathological findings the histological diagnosis of diffuse large B-cell lymphoma of the stomach with adjacent areas suggestive of MALT lymphoma was emitted.
Immunohistochemical study demonstrated in high-grade lymphoma zones the presence of a lymphoid infiltrate positive for CD79a, CD43 and CD38 markers, and negative for CD20, CD3, CD30, BCL-6 markers,
Thus, this study confirmed the diagnosis of diffuse large B-cell lymphoma, "activated variant", probably derived from adjacent MALT lymphoma.
1.
In 1983, Isaacson and Wright described the concept of mucosal-associated lymphoid tissue lymphoma (MALT) to explain the etiopathogeny of gastrointestinal tract lymphomas.
This is a type of extranodal non-Hodgkin's lymphoma that results from malignant transformation of B cells in the marginal zone.
The stomach is the most common location and accounts for approximately 24% of all primary extranodal lymphomas (17).
According to the criteria proposed by Dawson et al, it is considered that a gastric lymphoma is primary when the stomach is the organ predominantly affected and intra-abdominal adenopathies, if affected, correspond to lymphatic drainage.
Therefore, patients with peripheral and/or mediastinal lymphadenopathies, peripheral blood, hepatosplenic or bone marrow involvement should be excluded from the diagnosis of this disease (7,17).
Primary gastric lymphoma is rare, although its incidence is increasing (24).
At the time of diagnosis, it is a low-grade tumor in 45 cases; the rest correspond to high-grade malignant lymphomas.
In most cases it is located in the gastric antrum, although it can be multifocal in 33% of cases (19.20).
Multiple studies have shown that there is a close relationship between Hp infection and the development of gastric MALT lymphoma (21.25).
Normal gastric tissue lacks organized lymphoid tissue. Infection with this bacterium causes a subgroup of patients to develop lymphoid tissue associated with the mucosa (MALT tissue), lymphoid hyperplasia, and clonal expansion.
It is believed that Hp infection produces acute inflammation that progresses to chronic inflammation with increased lymphocytes, plasma cells and eosinophils.
In the progression of this chronic gastritis lymphoid follicles and lymphatic aggregates may appear, histological substrate necessary for the development of MALT lymphoma.
The tumor proliferation of B lymphocytes is secondary to a specific activation of T lymphocytes specifically reactivated, which are activated by Hp and host cytokines (25).
The most evident relationship between this microorganism and MALT lymphoma is given by regression of tumors after eradication of infection, initially described by S. aureus in 1993 and subsequently confirmed by multiple studies (21).
The division of lymphomas into "low grade" and "high grade" is established according to the proportion of blast cells present in the lesion (17).
This differentiation is important because the high grade involves a more aggressive clinical picture and a worse prognosis.
Histological diagnosis of the grade can be difficult in certain patients, since both can coexist in the same lesion or in different multifocal lesions.
In addition, some cases of progressive transformation from low to high grade have been described in some MALT lymphomas (18.19).
Thus, it is considered that the presence of islots of more than 20 transformed cells, or a proportion greater than 15-20% of high-grade cells in a low-grade lymphoma, has clinical significance.
On the contrary, in some high-grade lymphomas there is no sign of low-grade lesion, so these tumors can be considered "de novo" high-grade.
However, this finding lacks prognostic significance, since there were no clinical differences between the latter and those originating in a low-grade lymphoma.
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Anatomopathological diagnosis
Diffuse large B-cell lymphoma "activated variant" of the stomach, probably derived from adjacent MALT lymphoma.
1.
Corresponding address: Carolina Muñoz Codoceo.
Gastrointestinal Tract Medicine Department.
12 de Octubre University Hospital.
Avda. de Córdoba, s/n.
28041 Madrid. e-mail: carolviaje@hotmail.com
Rec. 09-01-07.
Accepted: 09-01-07.
