- Email: [email protected]
Histiocytic lymphoma of the cervix
GYNECOLOGIC
ONCOLOGY
8,
97-103 (1979)
CASE REPORT
Histiocytic ALAN Division
of Radiution
Therapy.
Lymphoma
of the Cervix
D. STEINFELD,
M.D.’
Malcolm Grow USAF Medical Washington, D.C. 20331
Center.
Andrelc~s
AFB,
Received August 7, 1978 Histiocytic lymphoma, when localized to a single extranodal site, can have a very good prognosis. A case of histiocytic lymphoma of the cervix is presented. This case, as well as other cervical lymphomas gleaned from the literature, is discussed with regard to clinical staging and evaluation of the patient. The roles of surgery. radiation therapy, and combined treatment are considered.
A malignant lymphoma, initially localized in the cervix, was first reported by Retikas in 1960 [I]. Since that time, a number of other cases have been reported [2-41. In 1974, Chorlton et al. [.5] reviewed the world’s literature on the subject and found 19 cases, to which he added 6 new reports. Recently, Delgado et ul. [6] described the M.D. Anderson experience with four patients having non-Hodgkin’s lymphoma of the cervix. Most of these reports have appeared in the gynecological literature as, understandably, the patients are often first seen and treated by a gynecologist. Early reports staged patients using the FIG0 system developed for squamous carcinoma of the cervix [7] and histological classification has frequently employed the nomenclature developed by Jackson and Parker (lymphosarcoma, reticulum cell sarcoma, giant follicular lymphoma). Recently, we have seen a patient who presented with a malignant lymphoma primary in the uterine cervix. The case is presented as a means of discussing the appropriate evaluation and staging of these patients. Additionally, the role of various therapeutic modalities will be considered. CASE REPORT
A 29-year-old Caucasian woman was well until 5 weeks prior to admission to the hospital when postcoital bleeding developed. The patient denied fever, night I To whom requests for reprints should be addressed: Department of Radiation Oncology, Rhode Island Hospital, Providence, R.I. 02902. 97 0090-8258/79/040097-07$01.00/O Copyright 0 1979 by Academic Press, Inc. All nghtr of reproduction in any form reserved.
98
ALAN
D.
STEINFELD
sweats, or weight loss. Significant in the past history is that the patient had rheumatic fever as a child and was on digoxin for paroxysmal atria1 tachycardia. Physical examination revealed a well-developed, Caucasian female in no acute distress. There was no peripheral lymphadenopathy. The lungs were clear to percussion and auscultation. Cardiovascular examination revealed a Grade III systolic ejection murmur, loudest at the apex. No abdominal organomegaly or masses were found. Pelvic examination revealed a 5-cm, barrel-shaped cervix without ulceration. There was a nodular thickening in the right parametrium. The remainder of the physical exam was normal. The patient underwent a fractional D&C and cervical conization, after an initial cervical biopsy and endocervical curettage showed entirely normal tissue. Curettings from the endocervix and endometrium were normal. The specimen from the cervical conization revealed diffuse histiocytic lymphoma (Fig. 1). Laboratory studies revealed a normal CBC, urinalysis, and liver function tests. The chest X ray, IVP, and barium enema were normal. A lymphangiogram revealed no pelvic or periaortic nodal disease. Bone marrow aspiration was normal. She underwent staging laparotomy at which time splenectomy, liver biopsies, and pelvic and periaortic lymph node biopsies were done. In addition, the stomach, bowel, and mesenteric nodes were inspected for signs of tumor. No additional disease was found. The patient was treated with external beam radiation followed by hysterectomy. The whole pelvis was treated to 4000 rad midline dose in 20 fractions using opposed fields with cobalt-60. Ten weeks following the completion of radiation, the patient underwent total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Pelvic examination prior to surgery revealed a minimally enlarged, though normal appearing cervix with no parametrial masses. No residual disease was found in the surgical specimen (Fig. 2). DISCUSSION
The development, by Rappaport [8], of a histopathological classification system for the non-Hodgkin’s lymphomas, allowed for the distinction between nodular and diffuse types and subclassification by cell type and degree of cellular differentiation. Jones et al. [9] showed that nodular and diffuse designations permitted separation of patients into favorable and unfavorable categories. Additionally, within each large group, survival was related to cell type. While Chorlton et al. employed a system similar to Rappaport’s, other reports, including the most recent, continue to use the older nomenclatures. This makes comparison with other lymphoma patients very difficult. Staging of patients with lymphomas of the cervix poses an interesting problem. Should the disease be staged as a primary gynecologic malignancy using the FIG0 system, or should it be staged as a lymphoma? The Ann Arbor (A.A.) modification of the Rye system is now widely accepted for staging Hodgkin’s disease (Table 1). The system has also been used successfully and with meaning in the nonHodgkin’s lymphomas. The A.A. modification employs the designation “E” for a localized extranodal site. Thus, primary lymphoma of the cervix, without evidence of nodal spread, is IE disease, rather than Stage IV. This point must be emphasized
HISTIOCYTIC
LYMPHOMA
OF
THE
CERVIX
99
100
ALAN
D.
STEINFELD
HISTIOCYTIC
LYMPHOMA
101
OF THE CERVIX
TABLE 1 ANN ARBOR LYMPHOMA STAGING Stage
Extent Nodal involvement within one region Single extralymphatic organ or site Nodal involvement within two or more regions, limited by the diaphragm Localized extranodal site and nodal involvement within one or more regions, limited by the diaphragm Nodal involvement of regions above and below the diaphragm with localized extralymphatic site with spleen involvement or with both Diffuse or disseminated involvement of one or more extralymphatic organs or tissue with or without lymph node involvement
as both the treatment and prognosis for Stage IV disease is significantly different. (The present case might be staged as IIE in light of the parametrial nodularity felt to represent tumor.) The role of the staging laparotomy in patients with non-Hodgkin’s lymphomas is still unclear. It has been found that in 60% of patients with abdominal disease, mesenteric nodes were involved. In our patient, the finding of mesenteric nodes would have significantly altered both her stage and her treatment. Because of the relative rarity of this disease no uniform treatment policy has been followed by the various authors. For purposes of comparison, the patients have been grouped as having been treated by surgery (Table 2), radiation (Table 3), or a combination of the two (Table 4). Additionally, it has been assumed that all patients described as having reticulum cell sarcoma would be classified as having diffuse histiocytic lymphoma. It is apparent that patients with histiocytic lymphoma confined to the cervix do well with a variety of therapies. This is in keeping with the excellent survival of other groups of patients with extranodal lymphomas, as noted by Chorlton et al. The question of what constitutes adequate treatment cannot be definitively answered by analyzing the few patients available. Some important observations can be made, however. The long-term survival seen in patients undergoing total hysterectomy without radiation suggests that this may be TABLE 2 SURGERY Author
Clinical stage
Treatment sequence
Survival
Delgado it ul. [6]
Cervix
Aaro et al. [ 1I] Chorlton et ul. [5]
Cervix Cervix Cervix
Radical hysterectomy and pelvic lymphadenectomy TAH and BSO TAH and BSO TAH
Dead with disseminated disease at 9 months NED at 8 years NED at 4.5 years NED at 10 years
102
ALAN
D. STEINFELD
TABLE 3 RADIATION THERAPY Author Delgado rt al. [6]
Vieaux and McGuire [3] Chorlton et al. [5]
Extent of disease
Treatment sequence
Cervix and upper vagina Cervix and anterior vagina
5000 radi25 Rx whole pelvis
NED at 2 years NED at 10 years
Cervix
5000 radi25 Rx whole pelvis and anterior vagina; 4000 r/20 Rx paraaortic and inguinal nodes; 4380 mg hr intracavitary radium 3500 radi20 Rx whole pelvis
Cervix and parametrium
Radiotherapy (type and dose not specified)
Dead with tumor at 2.5 years
Survival
NED at 3 years
TABLE 4 SURGERY AND RADIATION Author
Extent of disease
Delgado et (11. [6]
Cervix and upper vagina
Welch and Hellwig [4]
Cervix
Stransky et al. [2] Aaro et al. [II] Chorlton et al. [5]
Cervix
Lathrop [ 121
Present case
Cervix Cervix Cervix and upper vagina Cervix
Cervix and (R) parametrium
Treatment sequence
Survival
4000 rad/20 Rx whole pelvis; 6000 mg hr intracavity radium: TAH and BSO (no residual disease) Whole-pelvis radiation (4 fields each receiving 1600 rad; TAH and BSO (specimen showed necrotic tumor) TAH; 4000 rad whole pelvis
NED at 3 years
TAH and (R)SO: whole-pelvis irradiation and vaginal radium TAH; radiotherapy (type and dose not specified) TAH; radiotherapy (type and dose not specified) TAH, BSO, and pelvic node dissection (disease found in (R) parametrium and (R) ovary; 3400 rad whole pelvis) 4000 radi20 Rx whole pelvis; TAH and BSO (specimen showed no tumor)
NED at 1 year NED at 1 year 2 months NED at 6.5 years NED at 1.25 years Recurrence after 1 year Dead at 9 months with abdominal disease NED at 9 months
adequate treatment, when there is no extension of the disease beyond the cervix. Three patients, including the present case, underwent hysterectomy following courses of whole-pelvis radiation. No viable tumor was seen in any of the surgical specimens. This indicates that sterilization of the primary tumor is possible with acceptable doses of radiation. In light of this, there does not appear to be a pathophysiological reason to combine the two treatment modalities. For disease limited to the cervix, radiation or surgery should be adequate treatment. If there is parametrial or vaginal disease, radiation alone should suffice. Doses of 3500 to 4000 rad are sufficient to destroy
HISTIOCYTIC
LYMPHOMA
OF
THE
103
CERVIX
this tumor and yield good survival [IO]. There does not appear to be a need, therefore, for intracavitary radium to boost the dose to the vaginal vault and parametrium. ACKNOWLEDGMENTS The author gratefully mond in the preparation
acknowledges the assistance of this manuscript.
of Ms.
Mary
Homan
and
Ms.
Marilyn
Ham-
REFERENCES I. Retikas, D. G. Hodgkin‘s sarcoma of the cervix: Report of a case, Amc~r. J. Oh.stcr. Gyr~c~c,o/. 80, 1104-I 107 (1960). 2. Stransky, G. C., Acosta. A., Kaplan, A. L., and Friedman, J. A. Reticulum cell sarcoma of the cervix, Ohstc~!. G~n~c~o/. 41, 183-187 (1973). 3. Vieaux, J. W., and MC&ire, D. E. Reticulum cell sarcoma of the cervix, Awr-. J. Oh~~\tcr. Gymd. 89, 134- 13.5 (1964). 4. Welch, J. W., and Hellwig, C. A. Reticulum cell sarcoma of the uterine cervix: Report of a case, Oh.,tet. Gy/wo/. 22, 293-294 (1963). 5. Chorlton, I., Karnei, R. F., King. F. M.. and Norris, H. J. Primary malignant reticuloendothelial disease involving the vagina, cervix and corpus uteri. Ohsrc,~. G.vr~cc,o/. 44, 735-747 (1974). 6. Delgado. G., Smith. J. P.. Luis, D., and Gallagher, S. Reticulum cell sarcoma of the cervix. Amrr. J. Ohstc,r. Gy~w~1. 125, 691-694 (1976). 7. Kottmeier. H. L. The classification and staging of carcinoma of the uterus and vagina, .I. I/lr. F-d. Gyeco/. Ohtct. 1, 86-93 (1963). 8. Rappaport, H. T~nrors of thr hrnrc7topc’irfir. s~stcr,~, Armed Forces Institute of Pathology, Washington, D.C., pp. 91-206 (1966). 9. Jones. S. E., Fuks, Z.. Bull, M.. Kadin. M. E., Dorfman. R. F.. Kaplan. H. S., Rosenberg, S. A.. and Kim, H. Non-Hodgkin’s lymphomas. IV. Clinicopathologic correlation in 405 cases. Cancc~r- 31, 806-823 (1973). 10. Ultman, J. E., and Stein, R. S. Non-Hodgkin‘s lymphoma-An approach to staging and therapy. C‘cu7cc~r 25, 320-333 ( 1975). I I. Aaro. L. A., Symmonds, R. E.. and Dockerty, M. B. Sarcoma of the uterus, Amer. J. Ohsrc~r. G~r7ecol. 94, 101-109 (1966). 12. Lathrop, J. C. Malignant pelvic lymphoma. Oh.trc,r. G.vr7cc,c~o/. 30, 137-145 (1967).
ONCOLOGY
8,
97-103 (1979)
CASE REPORT
Histiocytic ALAN Division
of Radiution
Therapy.
Lymphoma
of the Cervix
D. STEINFELD,
M.D.’
Malcolm Grow USAF Medical Washington, D.C. 20331
Center.
Andrelc~s
AFB,
Received August 7, 1978 Histiocytic lymphoma, when localized to a single extranodal site, can have a very good prognosis. A case of histiocytic lymphoma of the cervix is presented. This case, as well as other cervical lymphomas gleaned from the literature, is discussed with regard to clinical staging and evaluation of the patient. The roles of surgery. radiation therapy, and combined treatment are considered.
A malignant lymphoma, initially localized in the cervix, was first reported by Retikas in 1960 [I]. Since that time, a number of other cases have been reported [2-41. In 1974, Chorlton et al. [.5] reviewed the world’s literature on the subject and found 19 cases, to which he added 6 new reports. Recently, Delgado et ul. [6] described the M.D. Anderson experience with four patients having non-Hodgkin’s lymphoma of the cervix. Most of these reports have appeared in the gynecological literature as, understandably, the patients are often first seen and treated by a gynecologist. Early reports staged patients using the FIG0 system developed for squamous carcinoma of the cervix [7] and histological classification has frequently employed the nomenclature developed by Jackson and Parker (lymphosarcoma, reticulum cell sarcoma, giant follicular lymphoma). Recently, we have seen a patient who presented with a malignant lymphoma primary in the uterine cervix. The case is presented as a means of discussing the appropriate evaluation and staging of these patients. Additionally, the role of various therapeutic modalities will be considered. CASE REPORT
A 29-year-old Caucasian woman was well until 5 weeks prior to admission to the hospital when postcoital bleeding developed. The patient denied fever, night I To whom requests for reprints should be addressed: Department of Radiation Oncology, Rhode Island Hospital, Providence, R.I. 02902. 97 0090-8258/79/040097-07$01.00/O Copyright 0 1979 by Academic Press, Inc. All nghtr of reproduction in any form reserved.
98
ALAN
D.
STEINFELD
sweats, or weight loss. Significant in the past history is that the patient had rheumatic fever as a child and was on digoxin for paroxysmal atria1 tachycardia. Physical examination revealed a well-developed, Caucasian female in no acute distress. There was no peripheral lymphadenopathy. The lungs were clear to percussion and auscultation. Cardiovascular examination revealed a Grade III systolic ejection murmur, loudest at the apex. No abdominal organomegaly or masses were found. Pelvic examination revealed a 5-cm, barrel-shaped cervix without ulceration. There was a nodular thickening in the right parametrium. The remainder of the physical exam was normal. The patient underwent a fractional D&C and cervical conization, after an initial cervical biopsy and endocervical curettage showed entirely normal tissue. Curettings from the endocervix and endometrium were normal. The specimen from the cervical conization revealed diffuse histiocytic lymphoma (Fig. 1). Laboratory studies revealed a normal CBC, urinalysis, and liver function tests. The chest X ray, IVP, and barium enema were normal. A lymphangiogram revealed no pelvic or periaortic nodal disease. Bone marrow aspiration was normal. She underwent staging laparotomy at which time splenectomy, liver biopsies, and pelvic and periaortic lymph node biopsies were done. In addition, the stomach, bowel, and mesenteric nodes were inspected for signs of tumor. No additional disease was found. The patient was treated with external beam radiation followed by hysterectomy. The whole pelvis was treated to 4000 rad midline dose in 20 fractions using opposed fields with cobalt-60. Ten weeks following the completion of radiation, the patient underwent total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Pelvic examination prior to surgery revealed a minimally enlarged, though normal appearing cervix with no parametrial masses. No residual disease was found in the surgical specimen (Fig. 2). DISCUSSION
The development, by Rappaport [8], of a histopathological classification system for the non-Hodgkin’s lymphomas, allowed for the distinction between nodular and diffuse types and subclassification by cell type and degree of cellular differentiation. Jones et al. [9] showed that nodular and diffuse designations permitted separation of patients into favorable and unfavorable categories. Additionally, within each large group, survival was related to cell type. While Chorlton et al. employed a system similar to Rappaport’s, other reports, including the most recent, continue to use the older nomenclatures. This makes comparison with other lymphoma patients very difficult. Staging of patients with lymphomas of the cervix poses an interesting problem. Should the disease be staged as a primary gynecologic malignancy using the FIG0 system, or should it be staged as a lymphoma? The Ann Arbor (A.A.) modification of the Rye system is now widely accepted for staging Hodgkin’s disease (Table 1). The system has also been used successfully and with meaning in the nonHodgkin’s lymphomas. The A.A. modification employs the designation “E” for a localized extranodal site. Thus, primary lymphoma of the cervix, without evidence of nodal spread, is IE disease, rather than Stage IV. This point must be emphasized
HISTIOCYTIC
LYMPHOMA
OF
THE
CERVIX
99
100
ALAN
D.
STEINFELD
HISTIOCYTIC
LYMPHOMA
101
OF THE CERVIX
TABLE 1 ANN ARBOR LYMPHOMA STAGING Stage
Extent Nodal involvement within one region Single extralymphatic organ or site Nodal involvement within two or more regions, limited by the diaphragm Localized extranodal site and nodal involvement within one or more regions, limited by the diaphragm Nodal involvement of regions above and below the diaphragm with localized extralymphatic site with spleen involvement or with both Diffuse or disseminated involvement of one or more extralymphatic organs or tissue with or without lymph node involvement
as both the treatment and prognosis for Stage IV disease is significantly different. (The present case might be staged as IIE in light of the parametrial nodularity felt to represent tumor.) The role of the staging laparotomy in patients with non-Hodgkin’s lymphomas is still unclear. It has been found that in 60% of patients with abdominal disease, mesenteric nodes were involved. In our patient, the finding of mesenteric nodes would have significantly altered both her stage and her treatment. Because of the relative rarity of this disease no uniform treatment policy has been followed by the various authors. For purposes of comparison, the patients have been grouped as having been treated by surgery (Table 2), radiation (Table 3), or a combination of the two (Table 4). Additionally, it has been assumed that all patients described as having reticulum cell sarcoma would be classified as having diffuse histiocytic lymphoma. It is apparent that patients with histiocytic lymphoma confined to the cervix do well with a variety of therapies. This is in keeping with the excellent survival of other groups of patients with extranodal lymphomas, as noted by Chorlton et al. The question of what constitutes adequate treatment cannot be definitively answered by analyzing the few patients available. Some important observations can be made, however. The long-term survival seen in patients undergoing total hysterectomy without radiation suggests that this may be TABLE 2 SURGERY Author
Clinical stage
Treatment sequence
Survival
Delgado it ul. [6]
Cervix
Aaro et al. [ 1I] Chorlton et ul. [5]
Cervix Cervix Cervix
Radical hysterectomy and pelvic lymphadenectomy TAH and BSO TAH and BSO TAH
Dead with disseminated disease at 9 months NED at 8 years NED at 4.5 years NED at 10 years
102
ALAN
D. STEINFELD
TABLE 3 RADIATION THERAPY Author Delgado rt al. [6]
Vieaux and McGuire [3] Chorlton et al. [5]
Extent of disease
Treatment sequence
Cervix and upper vagina Cervix and anterior vagina
5000 radi25 Rx whole pelvis
NED at 2 years NED at 10 years
Cervix
5000 radi25 Rx whole pelvis and anterior vagina; 4000 r/20 Rx paraaortic and inguinal nodes; 4380 mg hr intracavitary radium 3500 radi20 Rx whole pelvis
Cervix and parametrium
Radiotherapy (type and dose not specified)
Dead with tumor at 2.5 years
Survival
NED at 3 years
TABLE 4 SURGERY AND RADIATION Author
Extent of disease
Delgado et (11. [6]
Cervix and upper vagina
Welch and Hellwig [4]
Cervix
Stransky et al. [2] Aaro et al. [II] Chorlton et al. [5]
Cervix
Lathrop [ 121
Present case
Cervix Cervix Cervix and upper vagina Cervix
Cervix and (R) parametrium
Treatment sequence
Survival
4000 rad/20 Rx whole pelvis; 6000 mg hr intracavity radium: TAH and BSO (no residual disease) Whole-pelvis radiation (4 fields each receiving 1600 rad; TAH and BSO (specimen showed necrotic tumor) TAH; 4000 rad whole pelvis
NED at 3 years
TAH and (R)SO: whole-pelvis irradiation and vaginal radium TAH; radiotherapy (type and dose not specified) TAH; radiotherapy (type and dose not specified) TAH, BSO, and pelvic node dissection (disease found in (R) parametrium and (R) ovary; 3400 rad whole pelvis) 4000 radi20 Rx whole pelvis; TAH and BSO (specimen showed no tumor)
NED at 1 year NED at 1 year 2 months NED at 6.5 years NED at 1.25 years Recurrence after 1 year Dead at 9 months with abdominal disease NED at 9 months
adequate treatment, when there is no extension of the disease beyond the cervix. Three patients, including the present case, underwent hysterectomy following courses of whole-pelvis radiation. No viable tumor was seen in any of the surgical specimens. This indicates that sterilization of the primary tumor is possible with acceptable doses of radiation. In light of this, there does not appear to be a pathophysiological reason to combine the two treatment modalities. For disease limited to the cervix, radiation or surgery should be adequate treatment. If there is parametrial or vaginal disease, radiation alone should suffice. Doses of 3500 to 4000 rad are sufficient to destroy
HISTIOCYTIC
LYMPHOMA
OF
THE
103
CERVIX
this tumor and yield good survival [IO]. There does not appear to be a need, therefore, for intracavitary radium to boost the dose to the vaginal vault and parametrium. ACKNOWLEDGMENTS The author gratefully mond in the preparation
acknowledges the assistance of this manuscript.
of Ms.
Mary
Homan
and
Ms.
Marilyn
Ham-
REFERENCES I. Retikas, D. G. Hodgkin‘s sarcoma of the cervix: Report of a case, Amc~r. J. Oh.stcr. Gyr~c~c,o/. 80, 1104-I 107 (1960). 2. Stransky, G. C., Acosta. A., Kaplan, A. L., and Friedman, J. A. Reticulum cell sarcoma of the cervix, Ohstc~!. G~n~c~o/. 41, 183-187 (1973). 3. Vieaux, J. W., and MC&ire, D. E. Reticulum cell sarcoma of the cervix, Awr-. J. Oh~~\tcr. Gymd. 89, 134- 13.5 (1964). 4. Welch, J. W., and Hellwig, C. A. Reticulum cell sarcoma of the uterine cervix: Report of a case, Oh.,tet. Gy/wo/. 22, 293-294 (1963). 5. Chorlton, I., Karnei, R. F., King. F. M.. and Norris, H. J. Primary malignant reticuloendothelial disease involving the vagina, cervix and corpus uteri. Ohsrc,~. G.vr~cc,o/. 44, 735-747 (1974). 6. Delgado. G., Smith. J. P.. Luis, D., and Gallagher, S. Reticulum cell sarcoma of the cervix. Amrr. J. Ohstc,r. Gy~w~1. 125, 691-694 (1976). 7. Kottmeier. H. L. The classification and staging of carcinoma of the uterus and vagina, .I. I/lr. F-d. Gyeco/. Ohtct. 1, 86-93 (1963). 8. Rappaport, H. T~nrors of thr hrnrc7topc’irfir. s~stcr,~, Armed Forces Institute of Pathology, Washington, D.C., pp. 91-206 (1966). 9. Jones. S. E., Fuks, Z.. Bull, M.. Kadin. M. E., Dorfman. R. F.. Kaplan. H. S., Rosenberg, S. A.. and Kim, H. Non-Hodgkin’s lymphomas. IV. Clinicopathologic correlation in 405 cases. Cancc~r- 31, 806-823 (1973). 10. Ultman, J. E., and Stein, R. S. Non-Hodgkin‘s lymphoma-An approach to staging and therapy. C‘cu7cc~r 25, 320-333 ( 1975). I I. Aaro. L. A., Symmonds, R. E.. and Dockerty, M. B. Sarcoma of the uterus, Amer. J. Ohsrc~r. G~r7ecol. 94, 101-109 (1966). 12. Lathrop, J. C. Malignant pelvic lymphoma. Oh.trc,r. G.vr7cc,c~o/. 30, 137-145 (1967).