GYNECOLOGIC ONCOLOGY 40, 152-1.59 (1991)
The Sister (Mary) Joseph Nodule: Its Significance in Gynecology BHAGIRATH
MAJMUDAR,
M.D., AND
Department
of Gynecology
and Obstetrics
ANNE
A.
and Department
K.
WISKIND,
GATEWOOD
M.D., BARBARA N. M.D.
CROFT,
M.D.,
DUDLEY,
of Pathology,
Emory
University
School
of Medicine,
Atlanta,
Georgia
30322
Received May 11, 1990
Twenty-five cases of metastatic carcinoma of the umbilicus in women diagnosed and treated at Emory University Hospitals from 1973 to 1989 were reviewed, as were all previously reported cases in the English language literature. In our series, overall survival was greatest in patients treated with aggressive surgery and chemotherapy, compared with patients receiving no therapy or those treated with either surgery or adjunctive therapy alone. Individual survival was enhanced when the primary tumor site was of ovarian origin. 0 1991 Academic Press, Inc. INTRODUCTION
The “Sister Mary Joseph nodule” refers to a metastatic tumor of the umbilicus and is named after the Mayo Clinic nurse who first noticed its significance. A careful examination of the umbilicus can be helpful in detecting not only malignancy but also endometriosis, ectopic pregnancy, or gallbladder disease [l]. The importance of a thorough examination of the umbilicus should, therefore, not be overlooked. It will be helpful to remember that metastatic umbilical tumors can often be the first clinical sign of an underlying cancer or an indication of recurrence in a patient with known disease. Recently we witnessed a cluster of cases of umbilical nodules at our institution, which prompted our investigation into the pathology of umbilical malignancies and a historical review of this physical sign. MATERIALS
AND METHODS
All cases of carcinoma of the umbilicus in women diagnosed and treated at Emory University Affiliated Hospitals from 1973 to 1989 were sought. Their clinical charts and pathology records were reviewed. A special effort was made to update clinical course and survival of these patients.
152 0090-8258191$1.50 Copyright 0 1991 by Academic Press, Inc. All rights of reproduction in any form reserved
RESULTS
Vital Statistics Twenty-five women were found with well-documented metastatic tumors to the umbilicus (Table 1). There were no casesof primary umbilical malignancies identified. The average age of the patients was 62 years with a range of 3.5 to 89 years. The distribution of primary malignancies were ovary (11); pancreas (4); endometrium (3); colon (2); cervix (2); and one each of cecum, vulva, and uterine mixed Mullerian tumor. Clinical Signs and Symptoms Patients with metastatic umbilical tumors in this series presented with a variety of clinical signs and symptoms. In 10 patients the mass developed after the primary malignancy had been treated and the patients were being followed for the same (Table 2A). Three of these patients with ovarian cancer developed the nodule while undergoing chemotherapy. In the remaining 7 patients, the interval between the completion of treatment and the appearance of the umbilical nodule ranged from 2 months to 3 years, with an average of 12 months. Fifteen patients had umbilical metastasis at the time of diagnosis of their primary malignancy, and in all but one of these patients, the umbilical mass was the presenting complaint (Table 2B). One patient presented after a self-inflicted wound to remove the tumor of the umbilicus. The umbilical nodule in another patient had been incised and drained at an outside hospital for a presumed abscess prior to her presentation to our institution. One patient was originally felt to have an incarcerated hernia. Five patients had associated symptoms of epigastric pain, abdominal distention, weight loss, nausea, and vomiting.
153
THE SISTER (MARY) JOSEPH NODULE
TABLE 1 Clinicopathologic Features in Female Patients with Metastatic Carcinoma of the Umbilicus, Emory University Affiliated Hospitals: 1973-1989 Age 56 70 81 5s
Primary site _______ Uterus Endometrium Endometrium Endometrium
Microscopic Mixed Poorly Poorly Poorly
Survival
pathology
Y months, 7 days 2 months 3 months, 17 days 2 months
mullerian tumor differentiated adenocarcinoma differentiated adenocarcinoma differentiated adenocarcinoma
60 55 45 72 63 73 89 4s 62 35 78
Ovary Ovary Ovary Ovary Ovary Ovary Ovary Ovary Ovary Ovary Ovary
Adenocarcinoma Adenocarcinoma Papillary adenocarcinoma Papillary adenocarcinoma Papillary adenocarcinoma Papillary adenocarcinoma Adenocarcinoma, poorly Adenocarcinoma, poorly Adenocarcinoma, poorly Adenocarcinoma, poorly Adcnocarcinoma. poorly
70 56 54
Cervix (uterine) Cervix (uterine) Vulva
Squamous cell carcinoma Squamous cell carcinoma Squamous cell carcinoma
Y months 3 months, 3 days 17 days
50 57 60 64 75 72 59
Colon Colon Pancreas Pancreas Pancreas Pancreas Cecum
Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenosquamous Undifferentiated Adenocarcinoma
6 months, 15 days 4 months 4 days 37 days 2 months, 18 days 3 days 8.5 months
’ Survival measured from time of diagnosis of umbilical
Alive 1 year, 7 months 4 months, 21 days 11 months 10 days 11 months 14 months 11 days 1 year, 2 months, 7 days Alive 3 years, 2 months 16 months 2 years, 11 months, 20 days
differentiated differentiated differentiated differentiated differentiated
carcinoma carcinoma
metastasis.
Gross Clinical and Pathological
TABLE 2A Clinical Presentation of Patients with Metastatic Umbilical Tumors: Presentation of Umbilical Nodule during or after Initial Therapy Primary site Ovary Ovary
Ovary Ovary Cervix Cervix Endometrium Endometrium Vulva Colon
Clinical
signs and symptoms
Umbilical mass found after debulking, while on chemotherapy Umbilical mass developed after 3 debulkings, 8 courses intravenous chemotherapy, 4 courses intraperitoneal chemotherapy Umbilical mass developed 5 months after dcbulking and radiation therapy Periumbilical mass found during admission for sixth course of chemotherapy following initial debulking Umbilical mass 3 years after radiation therapy Umbilical mass 4 months after surgery and radiation Periumbilical mass 28 months after surgery and radiation Umbilical mass 2 months after radiation Umbilical lesion 9 months after radical vulvectomy Umbilical mass 2 months after surgery
Findings
The gross appearance of the lesion was highly variable. Unfortunately, in some cases the mass had incomplete clinical description which lacked objective criteria such as size, color, consistency, and mobility. In those cases in which measurements were available, the tumor size varied from 2 x 2 to 10 x 10 cm. Some were covered by apparently normal skin while others were necrotic and ulcerated with foul-smelling, purulent discharge and/or bleeding (Fig. 1). MICROSCOPIC FINDINGS Microscopic examination of the tumor showed adenocarcinoma in 19 cases (76%), with 4 of them showing mucin production by mucicarmine stain and 4 had papillary features (Table 1). A patient with a pancreatic primary demonstrated adenosquamous carcinoma, while another showed undifferentiated carcinoma. There were 3 cases of squamous cell carcinoma (12%), 2 originating from the cervix and one from the vulva. There was one case of mixed Mullerian tumor arising from the uterine corpus and invading the umbilicus.
154
MAJMUDAR
TABLE 2B Clinical Presentationof Patientswith MetastaticUmbilical Tumors: Presentationof Umbilical Nodule Prior to Therapy Primary site Ovary Ovary Ovary Ovary Ovary Ovary Ovary Pancreas Pancreas Pancreas Pancreas Endometrium Colon Cecum Uterus
Clinical signs and symptoms Umbilical nodule Abdominal wall mass, ascites Pleural effusion, abdominal mass Increasing umbilical mass, “hernia” Periumbilical mass Abdominal distention, pain, self-inflicted umbilical stab wound Weight loss, increasing abdominal girth, periumbilical node Epigastric pain, nausea, vomiting, periumbilical mass Bleeding from umbilicus Weight loss, epigastric pain, umbilical nodule, pelvic mass Ascites, pelvic mass Abdominal pain, pelvic mass, umbilical lymphadenopathy Vaginal bleeding, umbilical mass Fungating umbilical mass Umbilical mass, postmenopausal bleeding
ET AL.
death in 1939 as the director of a facility that was to become Mayo Clinic [2]. She is commonly credited as the first person to observe that firm nodules in the umbilicus on physical examination are associated with widespread intra-abdominal metastasis. Although this information was not published at the time, it was widely circulated in the surgical community. It was late Sir Hamilton Bailey, author of Physical Signs in Clinical Surgery, who first suggested this eponym to honor System Joseph [l]. There has been some controversy whether this eponym is correctly termed the Sister Joseph nodule or the Sister Mary Joseph nodule. This confusion is understandable as Sister Joseph’s given name before she joined the sisterhood was Mary, and she worked most of her career at St. Mary’s Hospital. However, the correct term is Sister Joseph nodule [3]. It is unknown why some patients with metastatic disease will develop umbilical nodules and others will not. Several
SURVIVAL Twenty-three of the 25 patients expired, with survival ranging from 3 days to 3 years from the time of diagnosis of the umbilical metastasis, with an overall average survival of 7.6 months. The survival was slightly better if the umbilical nodule was present prior to therapy with an average survival of 9.7 months (Table 3A), compared to 7.6 months in those patients developing nocules as an indication of treatment failure (Table 3B). Patients with an ovarian primary malignancy had the best overall survival (Table 4). A comparison of treatment modalities and survival (Tables 5 and 6) demonstrates that those patients treated aggressively with both surgery and adjunctive therapy have much better average survival (17.6 months) than patients treated with either surgery alone (average survival 7.4 months) or adjunctive therapy only (average survival 10.3 months). Patients who received no therapy had the lowest average survival of 2.3 months. Two of the patients in our series are still living, one more than 3 years and the other 20 months from the time of diagnosis of the umbilical metastasis. Both patients had an ovarian primary. The nodule was present at time of initial presentation in one patient and appeared as an indication of treatment failure in the other. Both patients have subsequently been treated aggressively. DISCUSSION Sister Joseph, after whom the metastatic tumors of the umbilicus have been named, served from 1889 until her
FIG. 1. A 4 x 4-cm ulcerating umbilical mass present for 3 months in a 55-year-old female. Biopsy revealed adenocarcinoma. At exploratory laparotomy an ovarian primary was discovered.
THE SISTER
(MARY)
JOSEPH
15.5
NODULE
TABLE 3A Summary of Treatment and Survival of Patients with Metastatic Umbilical Tumors Who Had Umbilical Metastasis Present Prior to Initial Therapy Primary site Ovary Ovary Ovary Ovary Ovary Ovary Ovary Pancreas Pancreas Pancreas Pancreas Endometrium Uterine Colon Cecum
Survival
Therapy None Surgical debulking with removal of umbilicus, chemotherapy Surgical debulking, chemotherapy Surgical debulking with bowel resection, chemotherapy Exploratory laparotomy with biopsies only, chemotherapy Exploratory laparotomy Surgical debulking, patient refused chemotherapy Exploratory laparotomy Chemotherapy Exploratory laparotomy None Total abdominal hysterectomy/bilateral salpingoophorectomy Chemotherapy Chemotherapy Right colectomy, 500 rad external beam radiation therapy
” From time of diagnosis of metastatic umbilical
11 days 14 months 11 months Alive 38 months 14 months 10 days 3 years 3 days 3 months 31 days 4 days 2 months 9 months 6.5 months 8.5 months Average = 9.7 months
tumor
pathways of spread are hypothetically possible. The most simplistic theory is of contiguous spread from intraperitoneal metastasis to the umbilicus, the thinnest part of the abdominal wall. However, the rich lymphatics and embryology of this region make other theories more intriguing. The major components of the umbilical cord in fetal life are the two umbilical arteries; the umbilical vein; the urachus, which passesfrom the fundus of the bladder to the umbilical cord; and the omphalomesenteric structures, which connect the intestinal tract to the umbilical cord. In adults, remnants of these structures are easy to recognize. The umbilical arteries are usually obliterated after birth. The umbilical vein extends superiorly from the cord into the liver and forms the falciform or suspensory ligament of the liver. The omphalomesenteric structures sometimes remain attached and patent, forming
a Meckel’s diverticulum [5]. Four sets of lymphatics pass from the umbilicus: (1) to the axillary lymph nodes, (2) the external inguinal nodes, (3) along the falciform ligament, and (4) to the deep inguinal nodes. Therefore, another theoretical route of metastasis includes retrograde lymphatic flow from the inguinal nodes or from nodes along the falciform ligament. Liver metastases are frequently present with Sister Joseph nodules, but whether the nodule causes spread to the liver or vice versa would be difficult to prove, especially since the liver is so commonly involved in metastatic disease. The obliterated umbilical arteries and the urachus could also provide pathways for spread; however, no documented report of a urinary tract malignancy with umbilical involvement is found in the literature [4,6]. Metastatic tumors of the umbilicus despite their mul-
TABLE 3B Summary of Treatment and Survival of Patients with Metastatic Umbilical Tumors Present as Evidence of Treatment Failure Additional
Primary site Ovary Ovary Ovary Ovary Endometrium Endometrium Colon Vulva Cervix Cervix
therapy”
Chemotherapy None Chemotherapy Phase II chemotherapy, surgical debulking None Exploratory laparotomy None None None External beam radiation therapy
” From time of diagnosis of metastatic umbilical
tumor.
Survival Alive after 20 months 4.5 months I I months 16 months 3.5 months 5 months 4 months 17 days 3 months 9 months Average = 7.6 months
156
MAJMUDAR
ET AL.
mulative experience found in the literature is the lack of gastric primaries and the preponderance of gynecologic primaries in our cases. Eighteen of 25 patients in our series had a gynecologic primary tumor, with 11 ovarian, Number of Average 3 endometrial, 2 cervical, and one uterine mixed MulPrimary tumor patients survival lerian and vulvar cancers compared with only 33 ovarian, Ovary” 12 months 11 endometrial, 2 fallopian tube, and 2 cervical primaries Pancreas 33.5 days in the series of 259 cases reported in the literature. This Endometrium 3.5 months may perhaps be attributed to the fact that we only evalColon 5 months uated cases in women, a sampling bias, or a decline of Cervix 6 months Vulva 17 days stomach cancer of the past decades [35]. Cecum 8.5 months Although umbilical malignancies are rare, primary umUterine mixed Mullerian 9 months bilical tumors are much more so compared to metastatic ’ Two patients with ovarian primary still living 1 year 7 months and tumors. Historically, the first large review by Cullen in 3 years 2 months after diagnosis of umbilical metastasis. 1916 on umbilical carcinoma had 22 cases of primary umbilical malignancies while 72 were due to metastatic disease [5]. A review of 667 cases of umbilical lesions by Barrow [18] showed 29.7% to be metastatic with an 8.4% tiple pathogenetic pathways are still uncommon. An exincidence of primary malignant tumors. The remaining tensive review of the English literature on the Sister Jocases were benign primary tumors or endometriosis. In seph nodule summarized in Table 7 shows a total of 259 Steck’s review of malignant umbilical tumors, 8 were pricasesof metastatic umbilical tumors [4-341. In this series, mary lesions while 40 were metastatic [17]. 133 patients were women (51%) and 111 were men Although primary carcinomas of the umbilicus are quite (43%); in 15 casesthe sex of the patient was not specified rare, they must always be included in the differential (6%). The primary malignancy was gastric in the majority of cases (77), followed in decreasing incidence by the diagnosis of umbilical growths. Primary carcinomas of the intestine (40), ovary (33), pancreas (23), endometrium umbilicus may be malignant melanomas secondary to (1 l), gallbladder (6), breast (6), prostate (2), fallopian preexisting nevi, basal cell carcinomas, or even adenotube (2), and cervix (2). Also reported are isolated cases carcinomas arising from remnants of the omphalomesenof carcinoma of the penis, liver, appendix, lung, and ma- teric duct. If these are widely excised, the patient usually lignant peritoneal mesothelioma and multiple myeloma has a good prognosis [5,17]. The prognosis associated with a metastatic umbilical metastasizing to the umbilicus. In 51 of the 259 cases, nodule is generally felt to be poor, with a mean survival the site of the primary tumor could not be determined. The large majority of the tumors were adenocarcinomas. of approximately 10 months from time of diagnosis The major difference between our series and the cu- [17,30,32]. Clements stated that the presence of a metTABLE 4 Summary of the Comparison of Survival with Primary Malignancy
TABLE 5A Comparison of Treatment Modalities and Survival in Patients with a Metastatic Umbilical Nodule Presenting Prior to Therapy Primary site Ovary Ovary Ovary Ovary Ovary Ovary Ovary Pancreas Pancreas Pancreas Pancreas Endometrium Uterine mixed Mullerian Colon Cecum
Surgery
Surgery and adjunctive therapy
-
+
-
t t
+ + +
-
+ + -
-
-
t
Adjunctive therapy
No therapy 14 months 11 days 11 months Alive 3 years 2 months 14 months 10 days 3 years 3 days 3 months 37 days 4 days
2 months Y months 6.5 months 8.5 months
157
THE SISTER (MARY) JOSEPH NODULE
TABLE 5B Comparison of Treatment Modalities and Survival in Patients with a Metastatic Umbilical Nodule Presenting during or after Initial Therapy Primary site
Surgery
Surgery and adjunctive therapy
Adjunctive therapy
astatic umbilical tumor “almost certainly establishes the inoperability of the patient” [12]. Warner concurred that such a patient quickly succumbs as the “disease has usually advanced beyond the pale of hope” [7]. However, this has not always proven to be the case, as long-term survivals have been reported. Powell’s review of 85 cases from the Mayo Clinic reports patient survival up to 3 years, with one patient alive 18 years after the diagnosis of an umbilical metastasis [30]. Two of 40 patients with metastatic umbilical tumors survived 30 and 45 months in Steck’s review of casesfrom the Armed Forces Institute of Pathology [17]. These findings led to his recommendation of immediate wide excision of these nodules followed by abdominal exploration. In a report by Sharaki and Abdel-Kader, 4 of 12 patients with metastatic umbilical tumors in their series survived 18 months to 3 years after aggressive surgical therapy [28]. In these cases the umbilical nodule was the only evidence of metastasis or recurrent disease. The remaining 8 patients had evidence of widespread disease and were given palliative therapy only. The results on their survival are not specified in this report. The therapy for patients with Sister Joseph nodules therefore remains controversial. Some advocate aggres-
TABLE 6 Summary of Treatment Modalities and Survival in Patients with Metastatic Umbilical Nodules
Surgery Surgery and adjunctive therapy Adjunctive therapy No therapy
Survival Still alive 1 year 7 months 4.5 months 11 months I6 months 3.5 months 5 months 4 months 17 days 3 months 9 months
Ovary Ovary Ovary Ovary Endometrium Endometrium Colon Vulva Cervix Cervix
Therapy
No therapy
Number of patients
Average survival
6 5 7 7
7.4 months 17.6 months 10.3 months 2.3 months
sive surgery with adjunctive therapy [1.5,17,28,32], while others feel that these patients should be considered for palliation only due to their poor prognosis [7,13,23,33]. The prognosis in patients with Sister Joseph nodules is variable and may be most directly affected by the primary tumor and cell type [32]. Patients with a pancreatic primary tumor generally do less well than those with an ovarian primary, who may have quite an extended survival. Contrary to previous reports that patients with metastatic tumor to the umbilicus should be offered palliation only [7,12,13,23,30,33], the experience in our institution indicates that survival may be significantly improved by a combination of surgery and adjunctive therapy. The patients treated aggressively with both surgery and adjunctive therapy had an average survival of 17.6 months, compared with those treated with either surgery alone (average survival 7.4 months) or adjunctive therapy only (average survival 10.3 months). Patients who received no therapy had the lowest average survival of 2.3 months. Of course, these findings may be influenced by a better overall state of health in patients selected for combination therapy compared with patients presenting in a very debilitated condition who are unable to tolerate aggressive therapy. In conclusion, we recommend that in all patients a careful examination of the umbilicus be performed, especially in those with known malignancies. All suspicious nodules should be biopsied to determine whether the nodule represents metastatic tumor and the primary site determined if possible by noninvasive methods. Treatment should be individualized to the primary tumor, cell type, and clinical condition of the patient. It may be advisable to treat some patients with advanced disease in a conservative way. Others, particularly those with disease of ovarian origin, should be considered for aggressive combination therapy to improve survival.
158
MAJMUDAR
ET AL.
TABLE I Metastatic Umbilical Nodules: A Review of the English Literature (Includes Males and Females) Year
Author
1864 1916 1917 1918 1926 1936 1945 1952 1952 1955 1964 1964 1964 1965 1966 1969 1969 1971 1974 1977 1980 1981 1981 1981 1981 1982 1984 1986 1987 1988 1988
Storer [4] Cullen [5] Wohl [6] warner [7] Head [8] Wilcox and Greenblatt [9] Lombardi and Parsons [lo] Riemenschneider and Miller (111 Clements [12] Schiebel et al. [ 131 Falkinburg and Savran [14] Horn et al. [15] O’Leary and O’Leary [16] Steck and Helwig [17] Barrow [ 181 Flynn and Spurrett [19] Couturier and Neale [ZO] Bank and Lieberman [Zl] Zeligman and Schwilm [22] Charoenkul et al. [23] Blumenthal [24] Galle et al. [25] Schnipper et al. [26] Miwa et al. [27] Sharaki and Abdel-Kader [28] Kwee et al. [29] Powell et al. [30] Goodhart et al. [31] Issa et al. [32] Cabellero et al. [33] Cooper et al. [34]
Totals
259 cases
0
Five breast, one lung, one prostate,
Stomach 27
Colorectal
Pancreas
Ovary
Endometrium
Fallopian tube
Gall-
bladder
5
Other
Unknown 1 21
5
I
1 6
2 6 3
I 1
-
4
9 -
1 1
-
1
1
-
-
1 -
16 1 1
-
40
23
9
I
33
11
2
1 8”
-
-
6
16
17 1
51
one cervix.
REFERENCES 1. Clain, A., Ed. Hamilton Bailey’s demonstration of physical signs in clinical surgery, IOP, Bristol, pp. 254-256 (1986). 2. Clapesattle, H. The Doctors Mayo, Univ. of Minnesota Press, Minneapolis, pp. 246-710 (1941). 3. Schwartz, I. S. Sister (Mary?) Joseph’s nodule, N. Engl. J. Med. 316, 1348-1349 (1987). 4. Storer, H. R. Cases illustrative of obstetric disease, Boston Med. Surg. J. 70, 73-74 (1864). 5. Cullen, T. S. Embryology, anatomy and diseases of the umbilicus, Saunders, Philadelphia, pp. l-65, 400-448 (1916). 6. Wohl, M. G. Carcinoma of the umbilicus, Boston Med. Surg. J. 17, 442-444 (1917). 7. Warner, F. Carcinoma of the umbilicus, Surg. Gynecol. Obstet. 27, 204-208 (1918). 8. Head, J. R. Cancer of the umbilicus secondary to cancer of the caecum, Surg. Gynecol. Obstet. 42, 356-358 (1926). 9. Wilcox, E. A., and Greenblatt, R. B. Umbilical cancer, Amer. J. Surg. 34, 116-118 (1936). 10. Lombardi, L. E., and Parsons, L. Carcinoma of the umbilicus metastatic from carcinoma of the stomach, Ann. Int. Med. 22, 290293 (1945).
11. Riemenschneider, E. A., and Miller, R. L. Adenocarcinoma of the uterus with metastases to the umbilicus, Amer J. Obstet. Gynecol. 64, 1385-1387 (1952). 12. Clements, A. B. Metastatic carcinoma of the umbilicus, JAMA 150, 556-559 (1956). 13. Schiebel, H. M., Cleaver, H. D., and Jackson, J. S. Metastatic carcinoma of the umbilicus, JAMA 157, 1489-1490 (1955). 14. Falkinburg, L. W., and Savran, J. Adenocarcinoma of the umbilicus secondary to carcinoma of the breast, Amer. J. Surg. 87, 795-797 (1964). 15. Horn, J. J., Fred, H. L., Lane, M., and Hudgins, P. T. Umbilical metastases, Arch. Int. Med. 114, 799-802 (1964). 16. O’Leary, J. L., and O’Leary, J. A. Carcinoma of the umbilicus, Amer. J. Obstet. Gynecol. 89, 136-137 (1964). 17. Steck, W. D., and Helwig, E. B. Tumors of the umbilicus, Cancer 18, 907-915 (1965). 18. Barrow, M. V. Metastatic tumors of the umbilicus, J. Chron. Dis. 19, 1113-1117 (1966). 19. Flynn, V. T., and Spurrett, B. R. Sister Joseph’s nodule, Med. J. Australia
1, 728-730 (1969).
20. Couturier, M. G., and Neale, R. C. Adenocarcinoma of umbilicus secondary to fallopian tube carcinoma, Amer. J. Obstet. Gynecol. 105, 32-33 (1969).
1.59
THE SISTER (MARY) JOSEPH NODULE 21. Bank, H., and Lieberman, S. 1. Sister Joseph’s nodule and malignant ascites in multiple myeloma, N. Engl. J. Med. 284, 676-677 (1971).
29.
22. Zeligman, I., and Schwilm, A. Umbilical metastasis from carcinoma of the colon, Arch. Dermafol. 110, 911-912 (1974). 23. Charoenkul, V., Del Campo, A., Derby, A., Hodgson, W. .I. B., and McElhinney, A. J. Tumors of the umbilicus, MI. Sinai J. Med. 44, 257-262 (1977).
30.
31.
24. Blumenthal. N. J. Umbilical tumors, 5. Afr. Med. J. 58, 457-458 (1980).
32.
25. Galle, P. C., Jobson, V. W., and Homesley, H. D. Umbilical metastasis from gynecologic malignancies: A primary carcinoma of the fallopian tube, Obstet. Gynecol. 57, 531-533 (1981).
33.
26. Schnipper. E. F., Nissenblatt, M. J., Schwartz, M., and Ludwig, S. L. Sister Mary Joseph node-A clue to internal malignancy. J. Med. Sot. New Jersey 78, 453-454 (1981).
27. Miwa, M., Matsumura, H.. Miwa, T., and Sato, S. A young gastric carcinoma patient with umbilical and scrotal metastasis, Tokai J. Exp. Clin. Med. 6, 305-308 (1981). 28. Sharaki, M.. and Abdel-Kader. M. Umbilical deposits from internal
malignancy (the Sister Joseph’s nodule). C/in. Oncol. 7, 351-355 (1981). Kwee, W. S.. Veldhuizen, R. W., Vermorken, J. B., Goldring, R. P., and Donner, R. Peritoneal mesothelioma presenting as umbilical tumor, Parho/. Res. Pratt. 174, 159-165 (1982). Powell, F. C., Cooper, A. J.. Massa, M. C., Goellner, J. R., and Su, W. P. D. Sister Mary Joseph’s nodule: A clinical and histologic study, J. Amer. Acad. Dermatol. 10, 610-615 (1984). Goodheart, R. S., Cooke, C. T., Tan, E., and Matz, L. R. Sister Mary Joseph’s nodule, Med. J. Aust. 145, 477-478 (1986). Issa, M., Freeley, M., Kerin, M., Tanner, A., and Keane, F. Umbilical deposits from internal malignancy: Sister Mary Joseph’s nodule, Ir. Med. J. 80, 152-153 (1987). Caballero, L. R., Lopez, F. V., Caballero, C. R., Hernando, S. U., Lopez, M. S., Yus, E. S., and Moro, B. H. Metastatic umbilical cancer-Sister Mary Joseph’s nodule: Report of two cases, J. Dermatol. Surg. Oncol
14, 664-667 (1988).
34. Cooper, J. P., Milligan, A., Graham-Brown, R. A. C., and Burns, D. A. Sister Mary Joseph’s nodule, Int. J. Dermatol. 27, 652-653 (198X). 35. Rubin. P.. Ed. Clinical oncology, American Cancer Society, p. 172 (1974).
The Sister (Mary) Joseph Nodule: Its Significance in Gynecology BHAGIRATH
MAJMUDAR,
M.D., AND
Department
of Gynecology
and Obstetrics
ANNE
A.
and Department
K.
WISKIND,
GATEWOOD
M.D., BARBARA N. M.D.
CROFT,
M.D.,
DUDLEY,
of Pathology,
Emory
University
School
of Medicine,
Atlanta,
Georgia
30322
Received May 11, 1990
Twenty-five cases of metastatic carcinoma of the umbilicus in women diagnosed and treated at Emory University Hospitals from 1973 to 1989 were reviewed, as were all previously reported cases in the English language literature. In our series, overall survival was greatest in patients treated with aggressive surgery and chemotherapy, compared with patients receiving no therapy or those treated with either surgery or adjunctive therapy alone. Individual survival was enhanced when the primary tumor site was of ovarian origin. 0 1991 Academic Press, Inc. INTRODUCTION
The “Sister Mary Joseph nodule” refers to a metastatic tumor of the umbilicus and is named after the Mayo Clinic nurse who first noticed its significance. A careful examination of the umbilicus can be helpful in detecting not only malignancy but also endometriosis, ectopic pregnancy, or gallbladder disease [l]. The importance of a thorough examination of the umbilicus should, therefore, not be overlooked. It will be helpful to remember that metastatic umbilical tumors can often be the first clinical sign of an underlying cancer or an indication of recurrence in a patient with known disease. Recently we witnessed a cluster of cases of umbilical nodules at our institution, which prompted our investigation into the pathology of umbilical malignancies and a historical review of this physical sign. MATERIALS
AND METHODS
All cases of carcinoma of the umbilicus in women diagnosed and treated at Emory University Affiliated Hospitals from 1973 to 1989 were sought. Their clinical charts and pathology records were reviewed. A special effort was made to update clinical course and survival of these patients.
152 0090-8258191$1.50 Copyright 0 1991 by Academic Press, Inc. All rights of reproduction in any form reserved
RESULTS
Vital Statistics Twenty-five women were found with well-documented metastatic tumors to the umbilicus (Table 1). There were no casesof primary umbilical malignancies identified. The average age of the patients was 62 years with a range of 3.5 to 89 years. The distribution of primary malignancies were ovary (11); pancreas (4); endometrium (3); colon (2); cervix (2); and one each of cecum, vulva, and uterine mixed Mullerian tumor. Clinical Signs and Symptoms Patients with metastatic umbilical tumors in this series presented with a variety of clinical signs and symptoms. In 10 patients the mass developed after the primary malignancy had been treated and the patients were being followed for the same (Table 2A). Three of these patients with ovarian cancer developed the nodule while undergoing chemotherapy. In the remaining 7 patients, the interval between the completion of treatment and the appearance of the umbilical nodule ranged from 2 months to 3 years, with an average of 12 months. Fifteen patients had umbilical metastasis at the time of diagnosis of their primary malignancy, and in all but one of these patients, the umbilical mass was the presenting complaint (Table 2B). One patient presented after a self-inflicted wound to remove the tumor of the umbilicus. The umbilical nodule in another patient had been incised and drained at an outside hospital for a presumed abscess prior to her presentation to our institution. One patient was originally felt to have an incarcerated hernia. Five patients had associated symptoms of epigastric pain, abdominal distention, weight loss, nausea, and vomiting.
153
THE SISTER (MARY) JOSEPH NODULE
TABLE 1 Clinicopathologic Features in Female Patients with Metastatic Carcinoma of the Umbilicus, Emory University Affiliated Hospitals: 1973-1989 Age 56 70 81 5s
Primary site _______ Uterus Endometrium Endometrium Endometrium
Microscopic Mixed Poorly Poorly Poorly
Survival
pathology
Y months, 7 days 2 months 3 months, 17 days 2 months
mullerian tumor differentiated adenocarcinoma differentiated adenocarcinoma differentiated adenocarcinoma
60 55 45 72 63 73 89 4s 62 35 78
Ovary Ovary Ovary Ovary Ovary Ovary Ovary Ovary Ovary Ovary Ovary
Adenocarcinoma Adenocarcinoma Papillary adenocarcinoma Papillary adenocarcinoma Papillary adenocarcinoma Papillary adenocarcinoma Adenocarcinoma, poorly Adenocarcinoma, poorly Adenocarcinoma, poorly Adenocarcinoma, poorly Adcnocarcinoma. poorly
70 56 54
Cervix (uterine) Cervix (uterine) Vulva
Squamous cell carcinoma Squamous cell carcinoma Squamous cell carcinoma
Y months 3 months, 3 days 17 days
50 57 60 64 75 72 59
Colon Colon Pancreas Pancreas Pancreas Pancreas Cecum
Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenosquamous Undifferentiated Adenocarcinoma
6 months, 15 days 4 months 4 days 37 days 2 months, 18 days 3 days 8.5 months
’ Survival measured from time of diagnosis of umbilical
Alive 1 year, 7 months 4 months, 21 days 11 months 10 days 11 months 14 months 11 days 1 year, 2 months, 7 days Alive 3 years, 2 months 16 months 2 years, 11 months, 20 days
differentiated differentiated differentiated differentiated differentiated
carcinoma carcinoma
metastasis.
Gross Clinical and Pathological
TABLE 2A Clinical Presentation of Patients with Metastatic Umbilical Tumors: Presentation of Umbilical Nodule during or after Initial Therapy Primary site Ovary Ovary
Ovary Ovary Cervix Cervix Endometrium Endometrium Vulva Colon
Clinical
signs and symptoms
Umbilical mass found after debulking, while on chemotherapy Umbilical mass developed after 3 debulkings, 8 courses intravenous chemotherapy, 4 courses intraperitoneal chemotherapy Umbilical mass developed 5 months after dcbulking and radiation therapy Periumbilical mass found during admission for sixth course of chemotherapy following initial debulking Umbilical mass 3 years after radiation therapy Umbilical mass 4 months after surgery and radiation Periumbilical mass 28 months after surgery and radiation Umbilical mass 2 months after radiation Umbilical lesion 9 months after radical vulvectomy Umbilical mass 2 months after surgery
Findings
The gross appearance of the lesion was highly variable. Unfortunately, in some cases the mass had incomplete clinical description which lacked objective criteria such as size, color, consistency, and mobility. In those cases in which measurements were available, the tumor size varied from 2 x 2 to 10 x 10 cm. Some were covered by apparently normal skin while others were necrotic and ulcerated with foul-smelling, purulent discharge and/or bleeding (Fig. 1). MICROSCOPIC FINDINGS Microscopic examination of the tumor showed adenocarcinoma in 19 cases (76%), with 4 of them showing mucin production by mucicarmine stain and 4 had papillary features (Table 1). A patient with a pancreatic primary demonstrated adenosquamous carcinoma, while another showed undifferentiated carcinoma. There were 3 cases of squamous cell carcinoma (12%), 2 originating from the cervix and one from the vulva. There was one case of mixed Mullerian tumor arising from the uterine corpus and invading the umbilicus.
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MAJMUDAR
TABLE 2B Clinical Presentationof Patientswith MetastaticUmbilical Tumors: Presentationof Umbilical Nodule Prior to Therapy Primary site Ovary Ovary Ovary Ovary Ovary Ovary Ovary Pancreas Pancreas Pancreas Pancreas Endometrium Colon Cecum Uterus
Clinical signs and symptoms Umbilical nodule Abdominal wall mass, ascites Pleural effusion, abdominal mass Increasing umbilical mass, “hernia” Periumbilical mass Abdominal distention, pain, self-inflicted umbilical stab wound Weight loss, increasing abdominal girth, periumbilical node Epigastric pain, nausea, vomiting, periumbilical mass Bleeding from umbilicus Weight loss, epigastric pain, umbilical nodule, pelvic mass Ascites, pelvic mass Abdominal pain, pelvic mass, umbilical lymphadenopathy Vaginal bleeding, umbilical mass Fungating umbilical mass Umbilical mass, postmenopausal bleeding
ET AL.
death in 1939 as the director of a facility that was to become Mayo Clinic [2]. She is commonly credited as the first person to observe that firm nodules in the umbilicus on physical examination are associated with widespread intra-abdominal metastasis. Although this information was not published at the time, it was widely circulated in the surgical community. It was late Sir Hamilton Bailey, author of Physical Signs in Clinical Surgery, who first suggested this eponym to honor System Joseph [l]. There has been some controversy whether this eponym is correctly termed the Sister Joseph nodule or the Sister Mary Joseph nodule. This confusion is understandable as Sister Joseph’s given name before she joined the sisterhood was Mary, and she worked most of her career at St. Mary’s Hospital. However, the correct term is Sister Joseph nodule [3]. It is unknown why some patients with metastatic disease will develop umbilical nodules and others will not. Several
SURVIVAL Twenty-three of the 25 patients expired, with survival ranging from 3 days to 3 years from the time of diagnosis of the umbilical metastasis, with an overall average survival of 7.6 months. The survival was slightly better if the umbilical nodule was present prior to therapy with an average survival of 9.7 months (Table 3A), compared to 7.6 months in those patients developing nocules as an indication of treatment failure (Table 3B). Patients with an ovarian primary malignancy had the best overall survival (Table 4). A comparison of treatment modalities and survival (Tables 5 and 6) demonstrates that those patients treated aggressively with both surgery and adjunctive therapy have much better average survival (17.6 months) than patients treated with either surgery alone (average survival 7.4 months) or adjunctive therapy only (average survival 10.3 months). Patients who received no therapy had the lowest average survival of 2.3 months. Two of the patients in our series are still living, one more than 3 years and the other 20 months from the time of diagnosis of the umbilical metastasis. Both patients had an ovarian primary. The nodule was present at time of initial presentation in one patient and appeared as an indication of treatment failure in the other. Both patients have subsequently been treated aggressively. DISCUSSION Sister Joseph, after whom the metastatic tumors of the umbilicus have been named, served from 1889 until her
FIG. 1. A 4 x 4-cm ulcerating umbilical mass present for 3 months in a 55-year-old female. Biopsy revealed adenocarcinoma. At exploratory laparotomy an ovarian primary was discovered.
THE SISTER
(MARY)
JOSEPH
15.5
NODULE
TABLE 3A Summary of Treatment and Survival of Patients with Metastatic Umbilical Tumors Who Had Umbilical Metastasis Present Prior to Initial Therapy Primary site Ovary Ovary Ovary Ovary Ovary Ovary Ovary Pancreas Pancreas Pancreas Pancreas Endometrium Uterine Colon Cecum
Survival
Therapy None Surgical debulking with removal of umbilicus, chemotherapy Surgical debulking, chemotherapy Surgical debulking with bowel resection, chemotherapy Exploratory laparotomy with biopsies only, chemotherapy Exploratory laparotomy Surgical debulking, patient refused chemotherapy Exploratory laparotomy Chemotherapy Exploratory laparotomy None Total abdominal hysterectomy/bilateral salpingoophorectomy Chemotherapy Chemotherapy Right colectomy, 500 rad external beam radiation therapy
” From time of diagnosis of metastatic umbilical
11 days 14 months 11 months Alive 38 months 14 months 10 days 3 years 3 days 3 months 31 days 4 days 2 months 9 months 6.5 months 8.5 months Average = 9.7 months
tumor
pathways of spread are hypothetically possible. The most simplistic theory is of contiguous spread from intraperitoneal metastasis to the umbilicus, the thinnest part of the abdominal wall. However, the rich lymphatics and embryology of this region make other theories more intriguing. The major components of the umbilical cord in fetal life are the two umbilical arteries; the umbilical vein; the urachus, which passesfrom the fundus of the bladder to the umbilical cord; and the omphalomesenteric structures, which connect the intestinal tract to the umbilical cord. In adults, remnants of these structures are easy to recognize. The umbilical arteries are usually obliterated after birth. The umbilical vein extends superiorly from the cord into the liver and forms the falciform or suspensory ligament of the liver. The omphalomesenteric structures sometimes remain attached and patent, forming
a Meckel’s diverticulum [5]. Four sets of lymphatics pass from the umbilicus: (1) to the axillary lymph nodes, (2) the external inguinal nodes, (3) along the falciform ligament, and (4) to the deep inguinal nodes. Therefore, another theoretical route of metastasis includes retrograde lymphatic flow from the inguinal nodes or from nodes along the falciform ligament. Liver metastases are frequently present with Sister Joseph nodules, but whether the nodule causes spread to the liver or vice versa would be difficult to prove, especially since the liver is so commonly involved in metastatic disease. The obliterated umbilical arteries and the urachus could also provide pathways for spread; however, no documented report of a urinary tract malignancy with umbilical involvement is found in the literature [4,6]. Metastatic tumors of the umbilicus despite their mul-
TABLE 3B Summary of Treatment and Survival of Patients with Metastatic Umbilical Tumors Present as Evidence of Treatment Failure Additional
Primary site Ovary Ovary Ovary Ovary Endometrium Endometrium Colon Vulva Cervix Cervix
therapy”
Chemotherapy None Chemotherapy Phase II chemotherapy, surgical debulking None Exploratory laparotomy None None None External beam radiation therapy
” From time of diagnosis of metastatic umbilical
tumor.
Survival Alive after 20 months 4.5 months I I months 16 months 3.5 months 5 months 4 months 17 days 3 months 9 months Average = 7.6 months
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ET AL.
mulative experience found in the literature is the lack of gastric primaries and the preponderance of gynecologic primaries in our cases. Eighteen of 25 patients in our series had a gynecologic primary tumor, with 11 ovarian, Number of Average 3 endometrial, 2 cervical, and one uterine mixed MulPrimary tumor patients survival lerian and vulvar cancers compared with only 33 ovarian, Ovary” 12 months 11 endometrial, 2 fallopian tube, and 2 cervical primaries Pancreas 33.5 days in the series of 259 cases reported in the literature. This Endometrium 3.5 months may perhaps be attributed to the fact that we only evalColon 5 months uated cases in women, a sampling bias, or a decline of Cervix 6 months Vulva 17 days stomach cancer of the past decades [35]. Cecum 8.5 months Although umbilical malignancies are rare, primary umUterine mixed Mullerian 9 months bilical tumors are much more so compared to metastatic ’ Two patients with ovarian primary still living 1 year 7 months and tumors. Historically, the first large review by Cullen in 3 years 2 months after diagnosis of umbilical metastasis. 1916 on umbilical carcinoma had 22 cases of primary umbilical malignancies while 72 were due to metastatic disease [5]. A review of 667 cases of umbilical lesions by Barrow [18] showed 29.7% to be metastatic with an 8.4% tiple pathogenetic pathways are still uncommon. An exincidence of primary malignant tumors. The remaining tensive review of the English literature on the Sister Jocases were benign primary tumors or endometriosis. In seph nodule summarized in Table 7 shows a total of 259 Steck’s review of malignant umbilical tumors, 8 were pricasesof metastatic umbilical tumors [4-341. In this series, mary lesions while 40 were metastatic [17]. 133 patients were women (51%) and 111 were men Although primary carcinomas of the umbilicus are quite (43%); in 15 casesthe sex of the patient was not specified rare, they must always be included in the differential (6%). The primary malignancy was gastric in the majority of cases (77), followed in decreasing incidence by the diagnosis of umbilical growths. Primary carcinomas of the intestine (40), ovary (33), pancreas (23), endometrium umbilicus may be malignant melanomas secondary to (1 l), gallbladder (6), breast (6), prostate (2), fallopian preexisting nevi, basal cell carcinomas, or even adenotube (2), and cervix (2). Also reported are isolated cases carcinomas arising from remnants of the omphalomesenof carcinoma of the penis, liver, appendix, lung, and ma- teric duct. If these are widely excised, the patient usually lignant peritoneal mesothelioma and multiple myeloma has a good prognosis [5,17]. The prognosis associated with a metastatic umbilical metastasizing to the umbilicus. In 51 of the 259 cases, nodule is generally felt to be poor, with a mean survival the site of the primary tumor could not be determined. The large majority of the tumors were adenocarcinomas. of approximately 10 months from time of diagnosis The major difference between our series and the cu- [17,30,32]. Clements stated that the presence of a metTABLE 4 Summary of the Comparison of Survival with Primary Malignancy
TABLE 5A Comparison of Treatment Modalities and Survival in Patients with a Metastatic Umbilical Nodule Presenting Prior to Therapy Primary site Ovary Ovary Ovary Ovary Ovary Ovary Ovary Pancreas Pancreas Pancreas Pancreas Endometrium Uterine mixed Mullerian Colon Cecum
Surgery
Surgery and adjunctive therapy
-
+
-
t t
+ + +
-
+ + -
-
-
t
Adjunctive therapy
No therapy 14 months 11 days 11 months Alive 3 years 2 months 14 months 10 days 3 years 3 days 3 months 37 days 4 days
2 months Y months 6.5 months 8.5 months
157
THE SISTER (MARY) JOSEPH NODULE
TABLE 5B Comparison of Treatment Modalities and Survival in Patients with a Metastatic Umbilical Nodule Presenting during or after Initial Therapy Primary site
Surgery
Surgery and adjunctive therapy
Adjunctive therapy
astatic umbilical tumor “almost certainly establishes the inoperability of the patient” [12]. Warner concurred that such a patient quickly succumbs as the “disease has usually advanced beyond the pale of hope” [7]. However, this has not always proven to be the case, as long-term survivals have been reported. Powell’s review of 85 cases from the Mayo Clinic reports patient survival up to 3 years, with one patient alive 18 years after the diagnosis of an umbilical metastasis [30]. Two of 40 patients with metastatic umbilical tumors survived 30 and 45 months in Steck’s review of casesfrom the Armed Forces Institute of Pathology [17]. These findings led to his recommendation of immediate wide excision of these nodules followed by abdominal exploration. In a report by Sharaki and Abdel-Kader, 4 of 12 patients with metastatic umbilical tumors in their series survived 18 months to 3 years after aggressive surgical therapy [28]. In these cases the umbilical nodule was the only evidence of metastasis or recurrent disease. The remaining 8 patients had evidence of widespread disease and were given palliative therapy only. The results on their survival are not specified in this report. The therapy for patients with Sister Joseph nodules therefore remains controversial. Some advocate aggres-
TABLE 6 Summary of Treatment Modalities and Survival in Patients with Metastatic Umbilical Nodules
Surgery Surgery and adjunctive therapy Adjunctive therapy No therapy
Survival Still alive 1 year 7 months 4.5 months 11 months I6 months 3.5 months 5 months 4 months 17 days 3 months 9 months
Ovary Ovary Ovary Ovary Endometrium Endometrium Colon Vulva Cervix Cervix
Therapy
No therapy
Number of patients
Average survival
6 5 7 7
7.4 months 17.6 months 10.3 months 2.3 months
sive surgery with adjunctive therapy [1.5,17,28,32], while others feel that these patients should be considered for palliation only due to their poor prognosis [7,13,23,33]. The prognosis in patients with Sister Joseph nodules is variable and may be most directly affected by the primary tumor and cell type [32]. Patients with a pancreatic primary tumor generally do less well than those with an ovarian primary, who may have quite an extended survival. Contrary to previous reports that patients with metastatic tumor to the umbilicus should be offered palliation only [7,12,13,23,30,33], the experience in our institution indicates that survival may be significantly improved by a combination of surgery and adjunctive therapy. The patients treated aggressively with both surgery and adjunctive therapy had an average survival of 17.6 months, compared with those treated with either surgery alone (average survival 7.4 months) or adjunctive therapy only (average survival 10.3 months). Patients who received no therapy had the lowest average survival of 2.3 months. Of course, these findings may be influenced by a better overall state of health in patients selected for combination therapy compared with patients presenting in a very debilitated condition who are unable to tolerate aggressive therapy. In conclusion, we recommend that in all patients a careful examination of the umbilicus be performed, especially in those with known malignancies. All suspicious nodules should be biopsied to determine whether the nodule represents metastatic tumor and the primary site determined if possible by noninvasive methods. Treatment should be individualized to the primary tumor, cell type, and clinical condition of the patient. It may be advisable to treat some patients with advanced disease in a conservative way. Others, particularly those with disease of ovarian origin, should be considered for aggressive combination therapy to improve survival.
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ET AL.
TABLE I Metastatic Umbilical Nodules: A Review of the English Literature (Includes Males and Females) Year
Author
1864 1916 1917 1918 1926 1936 1945 1952 1952 1955 1964 1964 1964 1965 1966 1969 1969 1971 1974 1977 1980 1981 1981 1981 1981 1982 1984 1986 1987 1988 1988
Storer [4] Cullen [5] Wohl [6] warner [7] Head [8] Wilcox and Greenblatt [9] Lombardi and Parsons [lo] Riemenschneider and Miller (111 Clements [12] Schiebel et al. [ 131 Falkinburg and Savran [14] Horn et al. [15] O’Leary and O’Leary [16] Steck and Helwig [17] Barrow [ 181 Flynn and Spurrett [19] Couturier and Neale [ZO] Bank and Lieberman [Zl] Zeligman and Schwilm [22] Charoenkul et al. [23] Blumenthal [24] Galle et al. [25] Schnipper et al. [26] Miwa et al. [27] Sharaki and Abdel-Kader [28] Kwee et al. [29] Powell et al. [30] Goodhart et al. [31] Issa et al. [32] Cabellero et al. [33] Cooper et al. [34]
Totals
259 cases
0
Five breast, one lung, one prostate,
Stomach 27
Colorectal
Pancreas
Ovary
Endometrium
Fallopian tube
Gall-
bladder
5
Other
Unknown 1 21
5
I
1 6
2 6 3
I 1
-
4
9 -
1 1
-
1
1
-
-
1 -
16 1 1
-
40
23
9
I
33
11
2
1 8”
-
-
6
16
17 1
51
one cervix.
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11. Riemenschneider, E. A., and Miller, R. L. Adenocarcinoma of the uterus with metastases to the umbilicus, Amer J. Obstet. Gynecol. 64, 1385-1387 (1952). 12. Clements, A. B. Metastatic carcinoma of the umbilicus, JAMA 150, 556-559 (1956). 13. Schiebel, H. M., Cleaver, H. D., and Jackson, J. S. Metastatic carcinoma of the umbilicus, JAMA 157, 1489-1490 (1955). 14. Falkinburg, L. W., and Savran, J. Adenocarcinoma of the umbilicus secondary to carcinoma of the breast, Amer. J. Surg. 87, 795-797 (1964). 15. Horn, J. J., Fred, H. L., Lane, M., and Hudgins, P. T. Umbilical metastases, Arch. Int. Med. 114, 799-802 (1964). 16. O’Leary, J. L., and O’Leary, J. A. Carcinoma of the umbilicus, Amer. J. Obstet. Gynecol. 89, 136-137 (1964). 17. Steck, W. D., and Helwig, E. B. Tumors of the umbilicus, Cancer 18, 907-915 (1965). 18. Barrow, M. V. Metastatic tumors of the umbilicus, J. Chron. Dis. 19, 1113-1117 (1966). 19. Flynn, V. T., and Spurrett, B. R. Sister Joseph’s nodule, Med. J. Australia
1, 728-730 (1969).
20. Couturier, M. G., and Neale, R. C. Adenocarcinoma of umbilicus secondary to fallopian tube carcinoma, Amer. J. Obstet. Gynecol. 105, 32-33 (1969).
1.59
THE SISTER (MARY) JOSEPH NODULE 21. Bank, H., and Lieberman, S. 1. Sister Joseph’s nodule and malignant ascites in multiple myeloma, N. Engl. J. Med. 284, 676-677 (1971).
29.
22. Zeligman, I., and Schwilm, A. Umbilical metastasis from carcinoma of the colon, Arch. Dermafol. 110, 911-912 (1974). 23. Charoenkul, V., Del Campo, A., Derby, A., Hodgson, W. .I. B., and McElhinney, A. J. Tumors of the umbilicus, MI. Sinai J. Med. 44, 257-262 (1977).
30.
31.
24. Blumenthal. N. J. Umbilical tumors, 5. Afr. Med. J. 58, 457-458 (1980).
32.
25. Galle, P. C., Jobson, V. W., and Homesley, H. D. Umbilical metastasis from gynecologic malignancies: A primary carcinoma of the fallopian tube, Obstet. Gynecol. 57, 531-533 (1981).
33.
26. Schnipper. E. F., Nissenblatt, M. J., Schwartz, M., and Ludwig, S. L. Sister Mary Joseph node-A clue to internal malignancy. J. Med. Sot. New Jersey 78, 453-454 (1981).
27. Miwa, M., Matsumura, H.. Miwa, T., and Sato, S. A young gastric carcinoma patient with umbilical and scrotal metastasis, Tokai J. Exp. Clin. Med. 6, 305-308 (1981). 28. Sharaki, M.. and Abdel-Kader. M. Umbilical deposits from internal
malignancy (the Sister Joseph’s nodule). C/in. Oncol. 7, 351-355 (1981). Kwee, W. S.. Veldhuizen, R. W., Vermorken, J. B., Goldring, R. P., and Donner, R. Peritoneal mesothelioma presenting as umbilical tumor, Parho/. Res. Pratt. 174, 159-165 (1982). Powell, F. C., Cooper, A. J.. Massa, M. C., Goellner, J. R., and Su, W. P. D. Sister Mary Joseph’s nodule: A clinical and histologic study, J. Amer. Acad. Dermatol. 10, 610-615 (1984). Goodheart, R. S., Cooke, C. T., Tan, E., and Matz, L. R. Sister Mary Joseph’s nodule, Med. J. Aust. 145, 477-478 (1986). Issa, M., Freeley, M., Kerin, M., Tanner, A., and Keane, F. Umbilical deposits from internal malignancy: Sister Mary Joseph’s nodule, Ir. Med. J. 80, 152-153 (1987). Caballero, L. R., Lopez, F. V., Caballero, C. R., Hernando, S. U., Lopez, M. S., Yus, E. S., and Moro, B. H. Metastatic umbilical cancer-Sister Mary Joseph’s nodule: Report of two cases, J. Dermatol. Surg. Oncol
14, 664-667 (1988).
34. Cooper, J. P., Milligan, A., Graham-Brown, R. A. C., and Burns, D. A. Sister Mary Joseph’s nodule, Int. J. Dermatol. 27, 652-653 (198X). 35. Rubin. P.. Ed. Clinical oncology, American Cancer Society, p. 172 (1974).
