Ovarian Neoplasm Versus Ovarian Lymphoma: A Literature Review with Focus on Radiology and Pathology Features
by Diana Donatello*
Radiologist, Indipendent Researcher Costa Contina Street 19, Vasto 66054, ITALY
*Corresponding author: Diana Donatello, MD, Radiologist, Indipendent Researcher Costa Contina Street 19, Vasto 66054, ITALY
Received Date: 27 December, 2023
Accepted Date: 02 January, 2024
Published Date: 05 January, 2024
Citation: Donatello D (2024) Ovarian Neoplasm Versus Ovarian Lymphoma: A Literature Review with Focus on Radiology and Pathology Features. Gynecol Obstet Open Acc 8: 176. https://doi.org/10.29011/2577-2236.100176
Introduction
Lymphomas are primary neoplasms of the immune system and arise within the lymphoid tissue with an incidence of approximately 8% of all neoplasms. They are divided into two groups represented by Hodgkin’s lymphomas, which owe their name to Thomas Hodgkin, an English doctor who discovered them in 1832, and the more heterogeneous group of non-Hodgkin’s lymphomas.
Hodgkin’s lymphomas, in addition to having a different histology compared to non-Hodgkin’s, generally present themselves as a nodal disease which continues to involve groups of adjacent lymph nodes, maintaining contiguity, with a low percentage of extranodal localizations which is between 2-5% of all Hodgkin lymphomas.
The areas most affected are the branches of the thoracic duct: supraclavicular, lateralcervical, mediastinal. Unlike nonHodgkin lymphomas, they do not maintain contiguity in their nodal presentation, but give rise to extranodal localizations with a frequency equal to 25-50% of all non-Hodgkin lymphomas and their spread is common.
They are divided into low- and high-level aggressive lymphomas. In non-Hodgkin lymphomas there is therefore a higher possibility of onset of the neoplastic pathology in precursors of lymphocytopoiesis that are located outside the secondary lymphoid organs, i.e. giving rise to extranodal manifestations.
By extranodal lymphoma we therefore mean either a lymphoma restricted to a single extranodal site and its regional lymph nodes, or a lymphoma which may be more widespread and in which an extranodal organ is the predominant site of the disease at which therapy may be primarily aimed [1] Virtually any organ may be affected by involvement extranodal, but the most commonly affected sites are the gastrointestinal tract, the skin, the central nervous system, the testis and a series of organs that are affected by the so-called lymphomas derived from the mucosaassociated lymphoid tissue (MALT) such as the stomach, salivary glands, the thyroid, the lung and the intestine.
Imaging techniques play a fundamental role in the noninvasive evaluation of patients with extranodal lymphoma, both for initial staging and during follow-up and in monitoring the response to treatment. In radiodiagnostics, the means most used in patients with lymphoma are ultrasound, CT, MRI and hybrid PET/CT.
In the past, evaluation and follow-up were mostly entrusted to CT alone, but nowadays hybrid PET/CT has proven to be the imaging tool with the highest sensitivity and specificity in the diagnosis, follow-up and restaging of lymphomas.
Lately, the use of Whole-Body Diffusion-Weighted MRI has been being tested in the evaluation of lymphoma and this technique, free of ionizing radiation, could become complementary to F18FDG PET/CT in the future, better safeguarding the patient’s health [1-4].
It is important to remember that the prevalence of lymphomas in the population is growing, consequently many more extranodal forms are observed in routine clinical practice, which is why it is important to make an early and most precise diagnosis of the neoplasm using the imaging techniques at our disposal [1]. This work specifically describes lymphomatous involvement of the ovary, which can present as primary or secondary in accordance with the definition of extranodal lymphoma.
Primary ovarian lymphoma is an extremely rare disease that occurs in 0.5% of all non-Hodgkin lymphomas and 1.5% of all ovarian cancers. Secondary lymphoma is generally the manifestation of disseminated lymphoma which occurs with a frequency of 7% of all lymphomas with systemic involvement [57].
On the other hand, although involvement of the genital tract by non-Hodgkin lymphoma is extremely rare, the ovary is the most frequently affected genital organ and secondary lymphoma at this site is the most common presentation. At the same time, information on the treatment and clinical figures of primary and secondary ovarian lymphoma is lacking [5-9]. As with all non-Hodgkin lymphomas, extranodal lymphoma with ovarian involvement can also be staged with the Ann Arbor classification (Table 1).
Stadio* |
Criteria |
I |
Only in one lymph node |
II |
In two or more lymph nodes on the same side of the diaphragm |
III |
In the lymph nodes, spleen, or both and on both sides of the diaphragm |
1 |
Above the renal vessels (e.g., spleen; splenic, hilar, celiac, and portal lymph nodes) |
2 |
In the lower abdominal region (lymph nodes) |
IV |
Extranodal involvement (eg, bone marrow, lung, liver) |
*Subclassification E indicates extranodal involvement adjacent to an involved lymph node (e.g., mediastinal lymph node disease and hilar adenopathy with adjacent pulmonary infiltration is classified as IIE). Stages can be further classified as A to indicate absence or B to indicate presence of constitutional symptoms (weight loss, fever, or night sweats). B symptoms typically occur with stages III and IV (20-30% of patients). |
Table 1: Ann Arbor staging for Hodgkin’s disease and for non-Hodgkin lymphomas.
It has been seen that the majority of primary ovarian lymphomas have a stage between I and II, therefore low grade, while in the case of a secondary lymphoma the stage is between III and IV, therefore a high grade. From this it can be deduced that the prognosis is better in primary lymphoma than in secondary lymphoma. However, we will see in the course of the discussion how the studies carried out on the survival of ovarian lymphoma are very complex and having a limited number of cases available, due to the rarity of the pathology, it is difficult to outline real statistics on the prognosis of these patients.
As regards histological representation, a greater prevalence of diffuse large B-cell ovarian lymphoma is evident, followed by follicular lymphoma, Burkitt’s lymphoma, anaplastic T-cell lymphoma and T-lymphoblastic precursors [10-19]. In the recent literature that we have analysed, several cases of primary and secondary ovarian diffuse large B-cell lymphoma are reported, which represents a clinically and biologically heterogeneous group of aggressive lymphomas which in many cases arises in extranodal sites such as the gastrointestinal tract, soft tissues, bone, breast, gonads and endocrine and exocrine tissues.
Follicular lymphoma is a small B-cell lymphoma that in most cases presents as a dissemination of nodal disease while it manifests as a primary lymphoma in a percentage of cases of 1015% and is well documented in sites such as the tract gastrointestinal tract, the testis, the thyroid, the breast, and the orbit [20,21]. Burkitt lymphoma is an aggressive lymphoma that can present at an extranodal site or as acute leukemia. It is a B-cell neoplasm that can be classified into three distinct clinical forms: endemic, sporadic and associated with immunodeficiency. The non-endemic form, also called American, has an abdominal presentation, often accompanied by ascites, with gastric, ileal, caecal, renal, ovarian, bone and central nervous system involvement [10-12,23,24].
Sometimes the presentation of Brurkitt’s lymphoma, like the onset of lymphoma pathology in general, can affect immunosuppressed subjects (for example HIV-positive subjects) or those who have undergone transplants (so-called post-transplant lymphoproliferative disorders) [23,25].
Aim of the study
The study we carried out has as its objective:
Outline the radiological aspects that best describe ovarian lymphoma, with particular attention to the differential diagnosis between lymphoma and other ovarian tumors, which may have a similar clinical and radiological presentation, underlining the importance of this distinction for the purposes of treatment.
This analysis is carried out a review of the literature.
Distinction between Primary, Secondary Lymphoma and Ovarian Cancer
Introduction
Malignant lymphoma of the female genital tract is unusual, however the ovaries are the most commonly affected site, with up to 25% of women with disseminated lymphoma having ovarian involvement [1].
Differences between Primary and Secondary Lymphoma
As we have said, ovarian involvement by lymphoma can be primary or secondary. The secondary can be of two types:
- an initial presentation of extra-ovarian occult disease
- a manifestation of a widely disseminated disease
The distinction is of considerable importance because primary extra-nodal lymphoma has a less aggressive course with a five-year survival rate of 80% compared to a disseminated malignant lymphoma which has a five-year survival rate of 33%. [5].
Ovarian lymphoma can present at any age, but the majority of affected women are around the age of 40. This type of lymphoma, whether primary or secondary, has various presentations, many of which are discovered incidentally during tests aimed at investigating problems concerning the abdominopelvic area, and present themselves in the form of abdominal or pelvic masses.
Even today it is difficult to ascertain whether an ovarian lymphoma is primary or secondary. In fact, the definition of primary lymphoma has been subject to controversy for years. Skodras et al [26], based on data from 15 cases of primary ovarian lymphoma, proposed that the definition of primary ovarian lymphoma should follow the following criteria:
- there is the presence of an ovarian mass, confined to one or both ovaries;
- lymphoma should be considered primary even if microscopic involvement of contiguous lymph nodes is detected;
- intraoperative and postoperative staging procedures do not reveal lymphoma in other parts of the body.
Talerman [27] states that even if there is local dissemination from the ovary to adjacent tissues, this manifestation should not preclude the diagnosis of primary lymphoma. On the other hand, Palagadu et al [28], argued that the criteria were too stringent and proposed that there should be a disease-free interval of at least 6 months after oophorectomy. Furthermore, some authors maintain that the reactive lymphocytes present in the ovary affected by lymphomatous pathology can secondarily populate the latter in response to various ovarian lesions, such as PID, endometriosis, benign and malignant neoplasms, and the most common luteal and follicular cysts [29]. However, there are many confirmed cases that present no evidence of inflammation either clinically or histologically [30].
Analysis of a clinical case diagnosed with secondary ovarian lymphoma: Below is an article, unique in its description, being the only case present in the literature that describes in detail, in the form of a “case report”, the difference between a primary and secondary ovarian lymphoma, given that their presentation clinical in most cases is identical.
Case Description
Crasta et al [5] report the case of a 44-year-old woman who presented with abdominal pain and dyspepsia lasting three months. The objective examination reveals the presence of a soft abdominal mass in the right iliac fossa, which appears to arise from the pelvis and extend above the navel. Transvaginal examination reveals the presence of a mass in the Douglas pouch pushing the uterus to the left side. Ultrasound examination of the abdominopelvic wall shows a mass in the right ovary and a second mass in the right iliac fossa. Eco-Doppler detects a fair vascularization of the masses and MRI shows hypointense images on T1 and hyperintense on T2. The patient undergoes a colonoscopy which reveals the presence of a large ulcerated submucosal nodule which occupies half the circumference and obstructs the lumen. All tumor markers are normal.
The biopsy reveals an inflammatory infiltrate in the lamina propria with many artifacts, so a definitive diagnosis cannot be made. Exploratory laparoscopy shows an intact and wellencapsulated tumor in the right ovary. The mass in the iliac fossa appears inflamed with the presence of pus in the paracolic recess, thickening of the intestinal wall and omental adhesions. Then the abscess is drained with subsequent salpingo - oophorectomy. The right ovarian mass measured 8.5 x 6.0 x 3.0 cm and was solid and whitish-gray in color.
The microscopic examination of the mass reveals that the ovarian tissue is covered by a diffuse carpet of medium-sized cells, with some large cells (Figure 1) in foci, forming cords and trabeculae. The cells have scant cytoplasm, nuclei with aggregated chromatin, and numerous nucleoli (Figure 2). The immunohistochemical examination highlights the presence of cells positive for LCA and negative for cytokeratin, therefore the diagnosis of non-Hodgkin lymphoma with ovarian, omental and peritoneal involvement is made (most likely a diffuse large B-cell lymphoma). The patient undergoes a CT scan for a post-operative check-up which detects multiple lymph node enlargements in the common iliac, internal iliac and external iliac groups. Bone marrow biopsy reveals no marrow infiltrates. The patient is subjected to a chemotherapy protocol which includes 6 cycles of CHOP, but despite the therapy there is progression of the lymphoma with subsequent renal and splenic involvement.
Figure 1: The image shows an ovarian tissue rich in medium volume cells, with large cells in foci, which form cords and trabeculae.