Ovarian lymphomas
December 15, 2017 | Author: Aysegul Uner | Category: N/A
Deskripsi Singkat
Arch Gynecol Obstet (2001) 265:91–93
© Springer-Verlag 2001
C A S E R E P O RT
C. Azizoglu · G. Altinok · A. Uner · C. Sokmensuer T. Kucukali · A. Ayhan
Ovarian lymphomas A clinicopathological analysis of 10 cases
Received: 21 June 2000 / Accepted: 12 September 2000
Abstract Analysis of 10 cases of Non-Hodgkin’s lymphoma with initial manifestation in the ovaries is presented with the histologic and immunohistochemical findings. Key words Non-Hodgkin’s lymphoma · Ovary · Immunophenotype
(L26), CD45RO (UCHL-1) and, CD 30 (Ki 1) (Dako). In some cases, histologic sections were also stained with the antibodies to cytokeratin, Vimentin, Desmin and, S-100. In all cases which expressed CD 45, alpha-naphtol chloroacetoesterase was measured to exclude a possibility of a myeloid neoplasm. For staging purposes both International Federation of Gynecology and Obstetrics (FIGO) and Ann Arbor staging systems were used [1, 4].
Results Introduction Secondary ovarian involvement by malignant lymphoma is often seen at the autopsy [2]. Deciding whether malignant lymphomas of the ovary are primary or secondary, is not always easy, especially in the advanced cases [7, 12]. Primary presentation as an ovarian mass is quite rare and applies to less than 1% of all lymphomas involving the ovary [2]. We report 10 patients with lymphoma who initially presented with bilateral or unilateral ovarian mass and discuss the clinicopathologic findings.
The clinical findings are summarized in Table 1. All patients presented with abdominal pain and/or a mass. One
Materials and methods 10 cases of malignant lymphoma presenting as a mass in one or both ovaries, were identified from the archives of the pathology department. These cases were treated in our hospital during the last 8 years. The medical records of these patients were reviewed. The routin Hematoxylin-eosin stained sections of these lymphoid neoplasms were re-evaluated with further immunohistochemical studies and re-classified according to the ‘‘REAL‘‘ classification. Immunohistochemical studies were performed on formaline-fixed and paraffin-embedded sections, using an avidin-biotin immunoperoxidase method and immunohistochemical panel consisted of the following monoclonal antibodies for identifying the immunophenotype of the neoplastic lymphocytes; CD 45 (LCA), CD 20 C. Azizoglu · G. Altinok (✉) · A. Uner · C. Sokmensuer T. Kucukali Department of Pathology, Hacettepe University School of Medicine, Yenimahalle 5, Durak, Çarsi cad. No:51, Ankara 06170, Turkey A. Ayhan Department of Gynecology and Obstetrics, Hacettepe University School of Medicine, Ankara, Turkey
Fig. 1 Diffuse infiltration of the ovarian stroma by the neoplastic lymphoid cells, H+E, 115X
92 Table 1 Clinical findings
Case
Age
Site of involvement
Clinical follow-up
ANN ARBOR
FIGO
1
27
both ovaries
IV
II
2
23
IV
IIIC
3
21
IV
IV
4
19
left ovary, colonic serosa both ovaries, liver, peritoneum both ovaries
no follow-up after 6 months of chemotheraphy died 7 months after the initial diagnosis no follow-up
5
54
6
19
7 8 9
16 19 30
10
60
both ovaries, omentum, serosa of fallopian tube both ovaries, fallopian tubes, vagina, cervix, ureter, Urinary bladder both ovaries both ovaries both ovaries, ileum, urinary bladder both ovaries, mesentery of ileum
meningeal carcinomatosis after 4 months no follow-up
IV
III
IV
III
died after 6 months
IV
III
no follow-up alive after 2 years alive after 5 months
IV IV IV
IIC IB IIC
alive after 2 months
IV
III
Discussion Ovarian involvement as a primary manifestation is a very rare symptom of Non-Hodgkin lymphomas [2]. Malignant ovarian lymphomas are in general a heterogenous group with different age ranges, clinical findings, site of involvement, histologic subtype, stage at the time of the diagnosis, and period of follow-up. Proposed diagnostic criterias for the primary ovarian lymphoma (POL) are as follows;
Fig. 2 Mononuclear cells composed of medium and large cells effacing the normal ovarian architecture, H+E, 460X
case initially presented with the systemic or ‘‘B” symptoms and represented an obvious secondary ovarian involvement. Another patient initially represented an apparent primary involvement as the neoplasm was solely confined to both ovaries (Fig. 1, 2). The rest of the cases were initially considered as be of uncertain origin. The patients who had no intraabdominal or pelvic dissemination, had a total abdominal hysterectomy with bilateral salphingoophorectomy, lymph node dissection and, resection of the metastases found in adjacent organs. The monoclonal antibodies, not spesific for the lymphocytes, were all negative except for one case displaying positive staining with both CD 45 and Vimentin. The histologic subtypes as well as the immunophenotypic analysis with the lymphocytic markers are summarized in Table 2.
(i) initially, absence of atypical cells in the bone marrow and peripheral blood, (ii) confinement of the neoplasm within the ovaries at the time of the diagnosis and, (iii) Distant neoplastic foci occuring at least several months later than the ovarian lesion [5]. Fullfilling the criterias above, a lymphoid neoplasm would still be primary even with a spread to immediately adjacent lymph nodes or a direct invasion of the immediately adjacent structures [3]. In addition to these, over 60 months of remission period after surgical treatment was also suggested as an adequate criteria for primary lymphoma of the ovary. Although ovarian involvement could appear as the first symptom, generalized dissemination usually occurs earlier in the secondary neoplasms [9]. After using these stringent criterias POL became very rare and only 20 cases were previously reported in the literature [3, 10]. Studies regarding the pathogenetic mechanisms of the POL revealed the presence of preexisting lymphoid tissue in variable amounts, and also showed that this was mainly associated with common ovarian lesions [7, 10]. Some authors suggested that these lymphoid aggregates were not native ovarian lymphocytes but that they represented an autoimmune and/or secondary reactive pro-
93 Table 2 Subtypes and immunohistochemical profiles
Case 1 2 3 4 5 6
IP immunophenotype, VIM vimentin
7 8 9 10
Histologic type
CD 45 (LCA)
CD 20
CD 45RO
CD 30 (Ki 1)
VIM
IP
follicular lymphoma grade II diffuse large cell diffuse large cell diffuse large cell follicular lymphoma grade II follicular lymphoma grade II Burkitt‘s lymphoma Burkitt‘s lymphoma diffuse large cell anaplastic large cell
+
+
–
–
+
B
+ + + +
+ + + +
– – – –
– – – –
– – – –
B B B B
+
+
–
–
–
B
+ + + +
+ + + –
– – – +
– – – +
– – – –
B B B T
cesses due to inflammation [6]. These studies support the hypothesis that malignant lymphoid neoplasms could arise in the ovary. So far the precursor lymphoid lesions were observed in the other organs, such as; thyroid, testis and, gastrointestinal tract but not in the ovaries [8]. Studies with immunohistochemistry displayed only scarce and weak expressions with the antibodies against to the estrogen and progesteron receptors [11]. Only one of our patients (case 8) presented with confined bilateral masses within the ovaries, histologically diagnosed as Burkitt’s lymphoma and two years following the surgery and adjuvant chemotheraphy, she is still alive and disease free. In general Burkitt’s lymphoma (diffuse small noncleaved cell lymphoma) occurs in higher percentages in children and young adults and these patients are frequently shown to have disseminated disease [7, 8]. It is not uncommon to diagnose Burkitt’s lymphoma as the initial manifestation of the disease and this always requires a meticulous search for systemic disease before diagnosing it as a primary neoplasm of the ovary. In the literature another case of Burkitt’s lymphoma treated with surgery was reported to have a long follow-up [8]. Epstein-Barr virus (EBV) plays a role in the pathogenesis of the Burkitt’s lymphoma and this could possibly lead to the formation of a secondary hyperimmune focus or induce a neoplastic transformation within the lymphoid tissue. As seen in the Mucosa Associated Lymphoid Tissue (MALT) lymphomas, an autoimmune precursor, such as autoimune oophoritis, or an infectious agent could also be considered in pathogenesis. Hypothetically, the adhesive molecules ‘‘home receptors” could cause a secondary lymphoid neoplasm to be confined to the ovary and behave similar to a primary neoplasm. Staging of the POLs are as difficult as categorizing them as primary and secondary. The Ann Arbor staging system is especially designed for Hodgkin’s disease and seems to be inadequate for the extranodal lymphomas. Bilateral involvement upgrades the staging as stage IV, despite the absence of involvement in the other sites. Therefore, we used both Ann Arbor and FIGO staging system as shown in Table 2. The patients diagnosed as stage I, have a favourable outcome after ablative surgery
with or without adjuvant chemotherapy [3]. One of our cases (case 8), with bilateral involvement (Ann Arbor stage IV) is still alive and disease free. Similar cases with bilateral involvement were also reported [10]. Therefore, FIGO system could be more beneficial over or at least accompany to the Ann Arbor system, or another better tailored system for the POL may be necessary.
References 1. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the committee on Hodgkin’s disease staging classification. Cancer Res 31:1860–1861 2. Chorlton I, Norris HJ, King FM (1974) Malignant reticuloendothelial disease involving the ovary as a primary manifestation: a series of 19 lymphomas and 1 granulocytic sarcoma. Cancer 34:397–407 3. Dao AH (1998) Malignant lymphoma of the ovary: report of a case successfully managed with surgery and chemotherapy. Gynecol Oncol 70:137–140 4. FIGO Cancer Committee (1986) Staging announcement. Gynecol Oncol 25:383–385 5. Fox H, Longley FA (1976) Malign lymphoma of ovary in: tumours of ovary. Heinemann, London, Chap 20, pp 293–299 6. Freeman C, Berg JW, Cutler SJ (1972) Occurrence and prognosis of extranodal lymphomas. Cancer 29:252–260 7. Monterroso V, Jaffe ES, Marino MJ, Medeiros LJ (1993) Malignant lymphomas involving the ovary. A clinicopathologic analysis of 39 cases. Am J Surg Pathol 17:154–170 8. Osborne BM, Robboy SJ (1983) Lymphomas or leukemia presenting as ovarian tumors; an analysis of 42 cases. Cancer 52:1933–1943 9. Paladugu RR, Bearman RM, Rappaport H (1980) Malignant lymphoma with primary manifestation in the gonad, a clinicopathologic study of 38 patients. Cancer 45:561–571 10. Skodras G, Fields V, Kragel PJ (1994) Ovarian lymphoma and serous carcinoma of low malignant potential arising in the same ovary. Arch Pathol Lab Med 118:647–650 11. Woodruff JD, Noli Castillo RD, Novak ER (1963) Lymphoma of the ovary: a study of 35 cases from the ovarian tumor registry of the American Gynecological Society. Am J Obstet Gynecol 85:912–918 12. Yamane T, Kirimoto K, Fujita M, Naka T, Tsubakio T, Ishikawa K, Nobunaga T, Tanaka F, Yamasaki M (1989) Ovarian involvement as an initial manifestation of malignant lymphoma. Jpn J Clin Oncol 19:163–166
Deskripsi
Arch Gynecol Obstet (2001) 265:91–93
© Springer-Verlag 2001
C A S E R E P O RT
C. Azizoglu · G. Altinok · A. Uner · C. Sokmensuer T. Kucukali · A. Ayhan
Ovarian lymphomas A clinicopathological analysis of 10 cases
Received: 21 June 2000 / Accepted: 12 September 2000
Abstract Analysis of 10 cases of Non-Hodgkin’s lymphoma with initial manifestation in the ovaries is presented with the histologic and immunohistochemical findings. Key words Non-Hodgkin’s lymphoma · Ovary · Immunophenotype
(L26), CD45RO (UCHL-1) and, CD 30 (Ki 1) (Dako). In some cases, histologic sections were also stained with the antibodies to cytokeratin, Vimentin, Desmin and, S-100. In all cases which expressed CD 45, alpha-naphtol chloroacetoesterase was measured to exclude a possibility of a myeloid neoplasm. For staging purposes both International Federation of Gynecology and Obstetrics (FIGO) and Ann Arbor staging systems were used [1, 4].
Results Introduction Secondary ovarian involvement by malignant lymphoma is often seen at the autopsy [2]. Deciding whether malignant lymphomas of the ovary are primary or secondary, is not always easy, especially in the advanced cases [7, 12]. Primary presentation as an ovarian mass is quite rare and applies to less than 1% of all lymphomas involving the ovary [2]. We report 10 patients with lymphoma who initially presented with bilateral or unilateral ovarian mass and discuss the clinicopathologic findings.
The clinical findings are summarized in Table 1. All patients presented with abdominal pain and/or a mass. One
Materials and methods 10 cases of malignant lymphoma presenting as a mass in one or both ovaries, were identified from the archives of the pathology department. These cases were treated in our hospital during the last 8 years. The medical records of these patients were reviewed. The routin Hematoxylin-eosin stained sections of these lymphoid neoplasms were re-evaluated with further immunohistochemical studies and re-classified according to the ‘‘REAL‘‘ classification. Immunohistochemical studies were performed on formaline-fixed and paraffin-embedded sections, using an avidin-biotin immunoperoxidase method and immunohistochemical panel consisted of the following monoclonal antibodies for identifying the immunophenotype of the neoplastic lymphocytes; CD 45 (LCA), CD 20 C. Azizoglu · G. Altinok (✉) · A. Uner · C. Sokmensuer T. Kucukali Department of Pathology, Hacettepe University School of Medicine, Yenimahalle 5, Durak, Çarsi cad. No:51, Ankara 06170, Turkey A. Ayhan Department of Gynecology and Obstetrics, Hacettepe University School of Medicine, Ankara, Turkey
Fig. 1 Diffuse infiltration of the ovarian stroma by the neoplastic lymphoid cells, H+E, 115X
92 Table 1 Clinical findings
Case
Age
Site of involvement
Clinical follow-up
ANN ARBOR
FIGO
1
27
both ovaries
IV
II
2
23
IV
IIIC
3
21
IV
IV
4
19
left ovary, colonic serosa both ovaries, liver, peritoneum both ovaries
no follow-up after 6 months of chemotheraphy died 7 months after the initial diagnosis no follow-up
5
54
6
19
7 8 9
16 19 30
10
60
both ovaries, omentum, serosa of fallopian tube both ovaries, fallopian tubes, vagina, cervix, ureter, Urinary bladder both ovaries both ovaries both ovaries, ileum, urinary bladder both ovaries, mesentery of ileum
meningeal carcinomatosis after 4 months no follow-up
IV
III
IV
III
died after 6 months
IV
III
no follow-up alive after 2 years alive after 5 months
IV IV IV
IIC IB IIC
alive after 2 months
IV
III
Discussion Ovarian involvement as a primary manifestation is a very rare symptom of Non-Hodgkin lymphomas [2]. Malignant ovarian lymphomas are in general a heterogenous group with different age ranges, clinical findings, site of involvement, histologic subtype, stage at the time of the diagnosis, and period of follow-up. Proposed diagnostic criterias for the primary ovarian lymphoma (POL) are as follows;
Fig. 2 Mononuclear cells composed of medium and large cells effacing the normal ovarian architecture, H+E, 460X
case initially presented with the systemic or ‘‘B” symptoms and represented an obvious secondary ovarian involvement. Another patient initially represented an apparent primary involvement as the neoplasm was solely confined to both ovaries (Fig. 1, 2). The rest of the cases were initially considered as be of uncertain origin. The patients who had no intraabdominal or pelvic dissemination, had a total abdominal hysterectomy with bilateral salphingoophorectomy, lymph node dissection and, resection of the metastases found in adjacent organs. The monoclonal antibodies, not spesific for the lymphocytes, were all negative except for one case displaying positive staining with both CD 45 and Vimentin. The histologic subtypes as well as the immunophenotypic analysis with the lymphocytic markers are summarized in Table 2.
(i) initially, absence of atypical cells in the bone marrow and peripheral blood, (ii) confinement of the neoplasm within the ovaries at the time of the diagnosis and, (iii) Distant neoplastic foci occuring at least several months later than the ovarian lesion [5]. Fullfilling the criterias above, a lymphoid neoplasm would still be primary even with a spread to immediately adjacent lymph nodes or a direct invasion of the immediately adjacent structures [3]. In addition to these, over 60 months of remission period after surgical treatment was also suggested as an adequate criteria for primary lymphoma of the ovary. Although ovarian involvement could appear as the first symptom, generalized dissemination usually occurs earlier in the secondary neoplasms [9]. After using these stringent criterias POL became very rare and only 20 cases were previously reported in the literature [3, 10]. Studies regarding the pathogenetic mechanisms of the POL revealed the presence of preexisting lymphoid tissue in variable amounts, and also showed that this was mainly associated with common ovarian lesions [7, 10]. Some authors suggested that these lymphoid aggregates were not native ovarian lymphocytes but that they represented an autoimmune and/or secondary reactive pro-
93 Table 2 Subtypes and immunohistochemical profiles
Case 1 2 3 4 5 6
IP immunophenotype, VIM vimentin
7 8 9 10
Histologic type
CD 45 (LCA)
CD 20
CD 45RO
CD 30 (Ki 1)
VIM
IP
follicular lymphoma grade II diffuse large cell diffuse large cell diffuse large cell follicular lymphoma grade II follicular lymphoma grade II Burkitt‘s lymphoma Burkitt‘s lymphoma diffuse large cell anaplastic large cell
+
+
–
–
+
B
+ + + +
+ + + +
– – – –
– – – –
– – – –
B B B B
+
+
–
–
–
B
+ + + +
+ + + –
– – – +
– – – +
– – – –
B B B T
cesses due to inflammation [6]. These studies support the hypothesis that malignant lymphoid neoplasms could arise in the ovary. So far the precursor lymphoid lesions were observed in the other organs, such as; thyroid, testis and, gastrointestinal tract but not in the ovaries [8]. Studies with immunohistochemistry displayed only scarce and weak expressions with the antibodies against to the estrogen and progesteron receptors [11]. Only one of our patients (case 8) presented with confined bilateral masses within the ovaries, histologically diagnosed as Burkitt’s lymphoma and two years following the surgery and adjuvant chemotheraphy, she is still alive and disease free. In general Burkitt’s lymphoma (diffuse small noncleaved cell lymphoma) occurs in higher percentages in children and young adults and these patients are frequently shown to have disseminated disease [7, 8]. It is not uncommon to diagnose Burkitt’s lymphoma as the initial manifestation of the disease and this always requires a meticulous search for systemic disease before diagnosing it as a primary neoplasm of the ovary. In the literature another case of Burkitt’s lymphoma treated with surgery was reported to have a long follow-up [8]. Epstein-Barr virus (EBV) plays a role in the pathogenesis of the Burkitt’s lymphoma and this could possibly lead to the formation of a secondary hyperimmune focus or induce a neoplastic transformation within the lymphoid tissue. As seen in the Mucosa Associated Lymphoid Tissue (MALT) lymphomas, an autoimmune precursor, such as autoimune oophoritis, or an infectious agent could also be considered in pathogenesis. Hypothetically, the adhesive molecules ‘‘home receptors” could cause a secondary lymphoid neoplasm to be confined to the ovary and behave similar to a primary neoplasm. Staging of the POLs are as difficult as categorizing them as primary and secondary. The Ann Arbor staging system is especially designed for Hodgkin’s disease and seems to be inadequate for the extranodal lymphomas. Bilateral involvement upgrades the staging as stage IV, despite the absence of involvement in the other sites. Therefore, we used both Ann Arbor and FIGO staging system as shown in Table 2. The patients diagnosed as stage I, have a favourable outcome after ablative surgery
with or without adjuvant chemotherapy [3]. One of our cases (case 8), with bilateral involvement (Ann Arbor stage IV) is still alive and disease free. Similar cases with bilateral involvement were also reported [10]. Therefore, FIGO system could be more beneficial over or at least accompany to the Ann Arbor system, or another better tailored system for the POL may be necessary.
References 1. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the committee on Hodgkin’s disease staging classification. Cancer Res 31:1860–1861 2. Chorlton I, Norris HJ, King FM (1974) Malignant reticuloendothelial disease involving the ovary as a primary manifestation: a series of 19 lymphomas and 1 granulocytic sarcoma. Cancer 34:397–407 3. Dao AH (1998) Malignant lymphoma of the ovary: report of a case successfully managed with surgery and chemotherapy. Gynecol Oncol 70:137–140 4. FIGO Cancer Committee (1986) Staging announcement. Gynecol Oncol 25:383–385 5. Fox H, Longley FA (1976) Malign lymphoma of ovary in: tumours of ovary. Heinemann, London, Chap 20, pp 293–299 6. Freeman C, Berg JW, Cutler SJ (1972) Occurrence and prognosis of extranodal lymphomas. Cancer 29:252–260 7. Monterroso V, Jaffe ES, Marino MJ, Medeiros LJ (1993) Malignant lymphomas involving the ovary. A clinicopathologic analysis of 39 cases. Am J Surg Pathol 17:154–170 8. Osborne BM, Robboy SJ (1983) Lymphomas or leukemia presenting as ovarian tumors; an analysis of 42 cases. Cancer 52:1933–1943 9. Paladugu RR, Bearman RM, Rappaport H (1980) Malignant lymphoma with primary manifestation in the gonad, a clinicopathologic study of 38 patients. Cancer 45:561–571 10. Skodras G, Fields V, Kragel PJ (1994) Ovarian lymphoma and serous carcinoma of low malignant potential arising in the same ovary. Arch Pathol Lab Med 118:647–650 11. Woodruff JD, Noli Castillo RD, Novak ER (1963) Lymphoma of the ovary: a study of 35 cases from the ovarian tumor registry of the American Gynecological Society. Am J Obstet Gynecol 85:912–918 12. Yamane T, Kirimoto K, Fujita M, Naka T, Tsubakio T, Ishikawa K, Nobunaga T, Tanaka F, Yamasaki M (1989) Ovarian involvement as an initial manifestation of malignant lymphoma. Jpn J Clin Oncol 19:163–166
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