GYNECOLOGIC ONCOLOGY 35, 399-405 ( 1989) CASE REPORT Metastatic Adenocarcinoma of the Cervix Presenting as an Inflammatory Breast Lesion ROBYN WARD, M.B.B.S., GREG CONNER, M.B.B.S., FRACP, WARICK DELPRADO, M.B.B.S., FRACP, AND DAVID DALLEY, M.B.B.S., FRACP Department qf Medical Oncology, St. Vincent’s Hospital, Victoria Street, Darlinghurst, NSW 2010, Australia Received October 10. 1988 The occurrence of an inflammatory breast lesion and wide- spread venous thrombosis in a woman with metastatic adeno- carcinoma of the endocervix is reported. Examination of biopsy specimens showed the inflammatory breast mass to be histolog- ically consistent with metastasis from the endocervix. Recurrent venous thrombosis requiring large doses of heparin for control of the phlebitis was also a feature of this patient’s illness. The disease was associated with elevation of serum CA 125 levels that did not parallel the patient’s clinical course. o 1989 Academic PWS, 1~. A 4%year-old postmenopausal woman was admitted to St. Vincent’s Hospital in June 1988 with a painful mass in her right breast. She had been well until 1984 when she developed a superficial thrombophlebitis of the left calf, which re- solved with bed rest. Phlebitis recurred in 1986 with involvement of the deep venous system of her left leg, necessitating warfarin therapy. Six months later she developed persistent PV bleeding, and examination under annesthesia revealed a stage IIB endocervical carcinoma, with a histological diagnosis of invasive, moderately differentiated papillary adenocar- cinema of the endocervical type (Fig. 1). An abdominal CT scan demonstrated enlarged paraaortic lymph nodes up to 1 cm in diameter, which were assumed to be path- ological. She was treated with radiotherapy to the pelvis (3500 rads) and paraaortic nodes (4800 rads) and under- went insertion of intravault cesium on two occasions. One year later she developed bilateral cervical lymph- adenopathy, together with a 2 x l-cm node in the right axilla. There was no clinical evidence of local recurrence of the endocervical carcinoma, and abdominal CT scan was normal. Biopsy of a left cervical node showed met- astatic moderately differentiated papillary adenocarci- noma of the serous type (Fig. 2). Serum CA 125 was noted to be elevated at 224 kU/liter (normal ~35). A differential diagnosis of metastatic adenocarcinoma of the endometrium, endocervix, or breast was considered and she was commenced on medroxyprogesterone ace- tate 400 mg/day. The patient was readmitted in June 1988following the rapid development of a swollen painful right breast. There was a 10 x 7-cm mass in the right breast, with reddening of the overlying skin and peau d’orange (Fig. 3). Cervical and right axillary lymphadenopathy was again noted and there were multiple subcutaneous nod- ules on the forearms and neck. The chronic edema of her lower limbs had worsened, and now extended over the anterior abdominal wall to the umbilicus. There was erythema and ulceration of the skin of the groin and lower abdomen in a pattern identical to that seen over the breast (Fig. 4). CA 125 was elevated at 204 kU/liter. Pelvic ultrasound showed right hydronephrosis, normal ovaries, and no evidence of pelvic lymphadenopathy. Bilateral iliac vein thromboses were demonstrated by Doppler ultra- sonograpy . Excision biopsy of a subcutaneous deposit on the right forearm as well as Tru-cut needle biopsy of the right breast once again revealed poorly differentiated papillary adenocarcinoma of the serous type (Fig. 5). Immuno- peroxidase stains for CA 125 performed on tissue from the right cubital fossa and the right breast were both positive (Fig. 6). Intravenous administration of heparin (60,000 U/day) was commenced, leading to a marked but transient im- provement in the lower limb edema. This was changed to subcutaneous heparin (10,000 U tds) prior to dis- 399 009@8258/89 $I.50 Copyright 0 IYXYby Academic Press. Inc. All rights of reproduction in any form reserved.
Transcript
GYNECOLOGIC ONCOLOGY 35, 399-405 ( 1989)
CASE REPORT Metastatic Adenocarcinoma of the Cervix Presenting as an
Department qf Medical Oncology, St. Vincent’s Hospital, Victoria Street, Darlinghurst, NSW 2010, Australia
Received October 10. 1988
The occurrence of an inflammatory breast lesion and wide- spread venous thrombosis in a woman with metastatic adeno- carcinoma of the endocervix is reported. Examination of biopsy specimens showed the inflammatory breast mass to be histolog- ically consistent with metastasis from the endocervix. Recurrent venous thrombosis requiring large doses of heparin for control of the phlebitis was also a feature of this patient’s illness. The disease was associated with elevation of serum CA 125 levels that did not parallel the patient’s clinical course. o 1989 Academic PWS, 1~.
A 4%year-old postmenopausal woman was admitted to St. Vincent’s Hospital in June 1988 with a painful mass in her right breast.
She had been well until 1984 when she developed a superficial thrombophlebitis of the left calf, which re- solved with bed rest. Phlebitis recurred in 1986 with involvement of the deep venous system of her left leg, necessitating warfarin therapy.
Six months later she developed persistent PV bleeding, and examination under annesthesia revealed a stage IIB endocervical carcinoma, with a histological diagnosis of invasive, moderately differentiated papillary adenocar- cinema of the endocervical type (Fig. 1). An abdominal CT scan demonstrated enlarged paraaortic lymph nodes up to 1 cm in diameter, which were assumed to be path- ological. She was treated with radiotherapy to the pelvis (3500 rads) and paraaortic nodes (4800 rads) and under- went insertion of intravault cesium on two occasions.
One year later she developed bilateral cervical lymph- adenopathy, together with a 2 x l-cm node in the right axilla. There was no clinical evidence of local recurrence of the endocervical carcinoma, and abdominal CT scan was normal. Biopsy of a left cervical node showed met- astatic moderately differentiated papillary adenocarci-
noma of the serous type (Fig. 2). Serum CA 125 was noted to be elevated at 224 kU/liter (normal ~35). A differential diagnosis of metastatic adenocarcinoma of the endometrium, endocervix, or breast was considered and she was commenced on medroxyprogesterone ace- tate 400 mg/day.
The patient was readmitted in June 1988 following the rapid development of a swollen painful right breast. There was a 10 x 7-cm mass in the right breast, with reddening of the overlying skin and peau d’orange (Fig. 3). Cervical and right axillary lymphadenopathy was again noted and there were multiple subcutaneous nod- ules on the forearms and neck. The chronic edema of her lower limbs had worsened, and now extended over the anterior abdominal wall to the umbilicus. There was erythema and ulceration of the skin of the groin and lower abdomen in a pattern identical to that seen over the breast (Fig. 4).
CA 125 was elevated at 204 kU/liter. Pelvic ultrasound showed right hydronephrosis, normal ovaries, and no evidence of pelvic lymphadenopathy. Bilateral iliac vein thromboses were demonstrated by Doppler ultra- sonograpy .
Excision biopsy of a subcutaneous deposit on the right forearm as well as Tru-cut needle biopsy of the right breast once again revealed poorly differentiated papillary adenocarcinoma of the serous type (Fig. 5). Immuno- peroxidase stains for CA 125 performed on tissue from the right cubital fossa and the right breast were both positive (Fig. 6).
Intravenous administration of heparin (60,000 U/day) was commenced, leading to a marked but transient im- provement in the lower limb edema. This was changed to subcutaneous heparin (10,000 U tds) prior to dis-
399 009@8258/89 $ I.50
Copyright 0 IYXY by Academic Press. Inc. All rights of reproduction in any form reserved.
400 WARD ET AL.
FIG. 1. Endocervical adenocarcinoma. H&E. x20.
FIG. 2. Lymph node deposit of papillary adenocarcinoma. H&E, X20.
CASE REPORT 401
FIG. 3. Inflammatory mass almost totally replacing right breast. Note the areolar ulceration and peau d’orange of the overlying skin.
402 WARD ET AL.
FIG. 4. Anterior abdominal wall and left groin showing ulceration and peau d’orange. This appearance is identical to that seen in the right breast.
charge. Tamoxifen had been started 2 weeks prior to this admission by her referring doctor on the assumption that this woman had developed an inflammatory breast car- cinoma. In view of the rapidly deteriorating clinical sta- tus, tamoxifen was stopped and chemotherapy with 4’- epirubicin, cyclophosphamide, and Muorouracil was administered. This had no effect on the rapid progression of this woman’s metastatic disease, and subsequent ad- ministration of cisplatin and mitomycin was also inef- fective. Her clinical course and treatment are illustrated in Fig. 7.
DISCUSSION
This woman had metastatic inflammatory adenocar- cinema of the endocervix associated with widespread venous thrombosis.
In view of her clinical history, recurrent adenocarci- noma of the endocervix was a possible source of her metastatic disease. It is well known that recurrent cer- vical cancer can present with distant metastases, the usual sites being the lung, bone, and liver [I]. As far as the
authors are aware, however, there are no reports of re- current endocervical cancer occurring in the breast.
The clinical features of this woman’s breast mass were characteristic of an inflammatory carcinoma of the breast, suggesting the breast as a primary site of her metastatic cancer. There is a known increased incidence of breast cancer in women with previous gynecological malignancy. Empiric therapy with tamoxifen was com- menced on this basis.
The elevated CA 125 suggested a third possibility, that of metastatic ovarian cancer. CA 125 is believed to be a mtillerian differentiation antigen [2] and is recognized by a monoclonal antibody originally raised against an ovarian cystadenocarcinoma [3]. It has thus been pro- posed to be of use in detecting gynecological tumors. This has been shown to be the case in ovarian cancer where more than 80% of surgically demonstrable non- mutinous epithelial cancers have elevated serum CA 125. In this case, however, no ovarian masses were demon- strable on ultrasound, and the possibility of metastatic ovarian cancer was therefore dismissed.
The source of metastatic disease in this woman was
CASE REPORT 403
FIG. 5. Poorly differentiated adenocarcinoma in the right breast. H&E. x IO. Note the normal breast in the left.
FIG. 6. Cell border staining for CA 125 (arrow) in the cubital fossa tumor. Immunoperoxidase CA 125, x40.
Summary of clinical course and treatment. Serum CA 125 levels were stable throughout the latter stages of her illness. Normal range for CA 125 is shown as the shaded area on the graph.
ultimately resolved by careful histological review of the biopsies. Three independent pathologists reported that biopsies from the breast, subcutaneous deposit, and cervical lymph node contained papillary serous adeno- carcinoma that was histologically similar to the original endocervical cancer which, although not of pure serous type, was largely papillary. It was on this basis that the final diagnosis of metastatic endocervical cancer was made. Both the breast biopsy and the subcutaneous de- posits stained with CA 125, supporting this diagnosis. Unfortunately, tissue from the original endocervical and lymph node biopsies was unavailable for immunoperox- idase staining with CA 125.
In addition to ovarian cancer, elevated levels of CA 125 have also been reported in adenocarcinomas of the fallopian tubes, endometrium and endocervix [3,41, breast, colon, and pancreas [4]. The level of CA 125 also parallels the clinical course of the disease in over 90% of cases [5] of ovarian cancer. Similarly, it has been proposed that CA 125 may be useful in monitoring pa- tients with carcinoma of the endometrium, endocervix, or fallopian tubes [3].
In the case of endometrial cancer there is some evi- dence to support this proposal. Duk et al. [4] showed that serum levels paralleled the clinical course in 121 patients, and increased pretreatment values were asso- ciated with a poorer outlook. CA 125 was consistently elevated in this patient, though it is noteworthy that the level did not increase as her clinical state worsened. This suggests that CA 125 may not be a useful marker of disease progression in endocervical cancer.
Metastatic spread of endocervical cancer to the breast is an unusual event that caused a degree of diagnostic confusion in this patient. Empirical therapy with tamox- ifen was commenced because of apparent inflammatory carcinoma of the breast. This was followed by a rapid
worsening of the thrombosis. There have been sporadic reports implicating tamoxifen in the development of ve- nous and arterial thrombosis [7,8]. It is possible that it contributed to the thromboses seen in this patient. Ve- nous thrombosis following the institution of therapy for malignancy is not uncommon and may be related to the release of various procoagulant factors from the tumor when it undergoes necrosis [9].
It is also quite likely that the recurrent and severe thrombotic episodes seen in this patient were associated with the malignancy per se, and were independent of the tamoxifen therapy. Venous thrombosis has long been associated with adenocarcinoma, this association being first described by Trousseau in 1865 [ 101.
It is of interest to note that our patient’s initial pre- sentation with the cervical malignancy was preceded by two episodes of venous thrombosis (one involving only superficial veins and one involving the veins of the deep system). Indeed, the vaginal hemorrhage that led to the initial diagnosis of her gynecological malignancy oc- curred during anticoagulant therapy. Bleeding episodes during anticoagulant therapy for venous thromboembo- lism have been shown to more common in patients with gynecological malignancy [I 1 I. Excessive bleeding in pa- tients with malignancy may also be associated with a low-grade symptomless intravascular coagulation 1121 which may be associated with tumor spread [12,131. There was, however, no evidence of such hematologic abnormalities in our patient.
The high dose of heparin required to achieve thera- peutic anticoagulation and control of the phlebitis in this patient is not unusual in malignancy-associated venous thrombosis, but despite the high doses of heparin re- quired, it is still preferred over warfarin anticoagulation in patients with malignancy-associated thrombosis, as the latter is often ineffective [14].
SUMMARY
We report the occurrence of an inflammatory breast lesion and widespread venous thrombosis in a woman with metastatic adenocarcinoma of the endocervix. The disease was associated with elevation of serum CA 125 levels that did not parallel the patient’s clinical course. We suggest that the diagnosis of metastatic endocervical cancer be entertained in patients with a past history of such malignancy who present with a subsequent breast lump that, on clinical grounds, resembles an inflamma- tory carcinoma of the breast.
ACKNOWLEDGMENTS
We thank Dr. R. Osborn, Westmead Hospital, for performing the immunoperoxidase stains and reviewing the histological slides, and Dr. J. Turner, St. Vincent’s Hospital, for reviewing the histological slides.
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