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CASE REPORT
Year : 2019  |  Volume : 12  |  Issue : 6  |  Page : 540-543  

Cytological diagnosis of metastatic ovarian carcinoma in a young female presenting as Sister Mary Joseph's Nodule


Department of Pathology, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India

Date of Submission28-Nov-2018
Date of Acceptance27-Feb-2019
Date of Web Publication17-Oct-2019

Correspondence Address:
Navatha Vangala
Department of Pathology, Nizams Institute of Medical Sciences, Hyderabad - 500 082, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_243_18

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  Abstract 


Sister Mary Joseph's nodule (SMJN) is a rare manifestation referring to a malignant metastatic umbilical nodule. It is a sign of advanced stage of malignancy and can be the earliest sign even before detection of primary malignancy. This case report describes a young female with metastatic high-grade ovarian serous carcinoma presenting as SMJN diagnosed on cytology.

Keywords: Fine-needle aspiration cytology, Sister Mary Joseph's nodule, umbilical metastasis


How to cite this article:
Ghodasara V, Vangala N, Roshni Paul T. Cytological diagnosis of metastatic ovarian carcinoma in a young female presenting as Sister Mary Joseph's Nodule. Med J DY Patil Vidyapeeth 2019;12:540-3

How to cite this URL:
Ghodasara V, Vangala N, Roshni Paul T. Cytological diagnosis of metastatic ovarian carcinoma in a young female presenting as Sister Mary Joseph's Nodule. Med J DY Patil Vidyapeeth [serial online] 2019 [cited 2019 Nov 16];12:540-3. Available from: http://www.mjdrdypv.org/text.asp?2019/12/6/540/269426




  Introduction Top


Sister Mary Joseph's nodule (SMJN) could be the first sign of intra-abdominal malignancy.[1] The most common primary sites are gastrointestinal malignancies (gastric, colonic, and pancreatic cancer) that account for more than 50% cases followed by gynecologic malignancies (ovarian and uterine cancer).[2] SMJN not only suggests the presence of malignancy but also indicates poor prognosis. Very few cases of SMJN were reported on cytology in literature and our case is the youngest female with ovarian serous carcinoma presenting with SMJN. The aim of this study is to emphasize the utility of fine-needle aspiration cytology (FNAC) in preoperative diagnosis of intra-abdominal malignancy presenting as SMJN.


  Case Report Top


A 25-year-old female presented to our hospital with 5-cm, painless, protuberant swelling over the umbilical region of 1-week duration. She was otherwise asymptomatic. She is P1 L1 with regular menstrual cycles. There was no significant family history.

On examination, there was a single, nontender, lump over umbilicus with brown-to-black discoloration of the skin with focal ulceration [Figure 1]. A midline cesarean scar was present just below the umbilical nodule. There was no inguinal lymphadenopathy. Informed consent was obtained from the patient to share the clinical information for publication.

With a clinical suspicion of omphalitis or pyogenic granuloma, FNAC was done using a 24-G needle attached to a 10-mL syringe. Air-dried smears were prepared for May–Grunwald–Giemsa staining and alcohol-fixed smears were prepared for Papanicolau, hematoxylin and eosin stains. On microscopy, smears were highly cellular and showed cells arranged in clusters, sheets, acinar, and papillary pattern. Cells were large with round-to-oval, pleomorphic, hyperchromatic nuclei and few showed prominent nucleoli with moderate eosinophilic cytoplasm. Occasional mitosis was seen. The background showed numerous hemosiderin-laden macrophages admixed with hemorrhage. It was reported as metastatic adenocarcinoma with a primary possibly from ovary or stomach [Figure 2]. Further evaluation with tumor markers and imaging were suggested.
Figure 1: Umbilical nodule with brown-to-black discoloration of the skin and focal ulceration

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Figure 2: Cytology of umbilical nodule – (a) cellular smears with papillary pattern and nests (MGG, ×100), (b) cells with round-to-oval, pleomorphic, hyperchromatic nuclei in acinar pattern, and (c) occasional mitosis (arrow) (MGG, ×400)

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An upper and lower gastrointestinal endoscopy was performed and showed no major abnormalities. Her CA125 levels were 310 U/mL (normal range: 0–35 units/mL). Other tumor markers such as carcinoembryonic antigen and carbohydrate antigen 19-9 were normal. Incisional biopsy from the umbilical growth was done which on microscopy showed skin lined by stratified keratinized epithelium with ulceration and an underlying lesion. The lesional cells were arranged in cribriform pattern, nests, cords, and islands. The cells were polygonal with round-to-oval pleomorphic, hyperchromatic nucleus, and moderate amount of cytoplasm with frequent mitosis [Figure 3]. Immunohistochemistry showed positivity for P53, WT1, and CK7 and was negative for CK20 within the lesional cells [Figure 4]. It was reported as metastatic high-grade ovarian serous carcinoma. On further evaluation, contrast-enhanced computed tomography abdomen showed well-defined, heterogeneously enhancing, soft-tissue density lesions in both the ovaries and in the anterior parietal wall with multiple nodal deposits. A radiological impression of ovarian malignancy with metastases was given. She was treated with neoadjuvant chemotherapy (NACT) with four cycles of carboplatin and paclitaxel with a progressive decline in CA125 levels. Post-NACT, she underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy with resection of umbilical and omental tumors. Histopathological examination revealed regression with areas of fibrosis and hyalinization in umbilical and omental resections as well as within nodal deposits. However, bilateral ovaries revealed residual high-grade serous carcinoma with a chemotherapy response Score 2. Postoperative period was uneventful and she is on regular follow-up.
Figure 3: Histopathology – (a) skin with underlying lesional cells arranged in nests and islands (H and E, ×100), (b) malignant cells with round-to-oval pleomorphic nucleus and prominent nucleolus, and (c) mitosis (arrow) (H and E, ×400)

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Figure 4: Immunohistochemistry – CK7, P53, and WT1 are positive; CK20 is negative (×400)

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  Discussion Top


Cutaneous metastasis from primary internal organ malignancy is an uncommon finding seen in 1%–3% of cases. According to the study by Lookingbill et al., only 5% of cases with intra-abdominal malignancy developed cutaneous metastasis.[3]

Umbilical tumors can be classified as benign or malignant. Benign lesions include umbilical hernia, granuloma, abscess, mycosis, cutaneous endometriosis, and eczema.[4] Published studies reveal that only 12% of umbilical neoplasms were primary skin tumors, rest being metastasis. Metastatic umbilical nodule called as SMJN was first described in the literature by Sister Mary Joseph Dempsey (1856–1939),[5] surgical assistant to Dr. William James Mayo. She drew attention to the presence of umbilical nodule in a patient being prepared for surgery. The presentation of a SMJN varies from soft-to-hard nodule with or without ulceration.[4] The age range is 18–87 years with female preponderance.[6] Our case is the youngest female in reproductive age group, reported in the literature and overall, the second youngest case with umbilical metastasis next to 12-year-old female reported by Albano and Kanterwhich was a metastatic desmoplastic small round cell tumor.[7]

SMJN is usually associated with primary neoplasm of the gastrointestinal tract (52%), followed by the female genital tract or genitourinary tract (28%) or unknown origin (18%–20%).[8] Majority of cases are of gastric[9] or ovarian origin, the other sites being appendix and gall bladder.[2] Endometrium and pancreatobiliary tree[9],[10] are the other two common primary sites in females. The majority of the cases of SMJN are adenocarcinomas, but cases of undifferentiated carcinomas, carcinoids, leiomyosarcomas, and small-cell carcinomas of the lung have also been noted.[6]

Mechanism of metastatic spread to the umbilicus likely includes direct transperitoneal spread, lymphatic spread through lymphatics along the obliterated umbilical vein, or hematogenous spread. It can also spread by remnant structures such as the falciform ligament, median umbilical ligament, or remnants of the vitelline duct. Contiguous extension to periumbilical skin could be also be suggested due to its proximity to intra-abdominal and pelvic structures.[6],[7] The SMJN is associated with a poor prognosis[2] with a 1-year survival rate of 13.5%.[6] Very few cases of SMJN in literature were reported on cytology. In our case, FNAC of umbilical nodules was the first investigation, and subsequently, she was investigated for the primary tumor. On cytology, highly cellular smears, cells arranged in acinar and papillary pattern, nuclear pleomorphism with irregular nuclear chromatin, and prominent nucleoli are the typical features of ovarian serous carcinoma. IHC plays a major role in differentiating metastatic carcinomas. CK7 positive, CK20 negative tumors include carcinoma of the lung, thyroid, breast, salivary gland, cervix, endometrium, as well as serous ovarian carcinomas and exclude metastatic colorectal adenocarcinoma.[11] P53 and WT1 are markers of ovarian serous carcinoma which were positive in this case. WT1 is a useful marker that helps in typing primary surface epithelial tumors of the ovary and helps to differentiate it from metastatic colorectal and endometrial carcinomas.[12] p53 gene is mutated in over 96% of cases in high-grade serous ovarian carcinomas, which is the most common subtype of ovarian cancer.[13],[14] The diagnosis is further substantiated by the clinical findings such as raised CA125 levels and an ovarian mass on imageology. Using FNAC, Handa et al. identified primary in five cases presenting as SMJN in a 5-year study period.[10] This case report highlights the cytological features of ovarian carcinoma in correlation with biochemical and imageological findings.


  Conclusion Top


FNAC is a safe, cheap, accurate procedure and can be the first-line investigation in preoperative diagnosis of metastatic umbilical nodules such as SMJN. Although rare, SMJN is a useful sign to search for intra-abdominal malignancy and a poor prognostic factor. Immediate workup with early diagnosis and treatment can be life-saving.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Tso S, Brockley J, Recica H, Ilchyshyn A. Sister Mary Joseph's nodule: An unusual but important physical finding characteristic of widespread internal malignancy. Br J Gen Pract 2013;63:551-2.  Back to cited text no. 1
    
2.
Sethi K, Shareef N, Bloom S. The Sister Mary Joseph nodule. Br J Hosp Med (Lond) 2018;79:C27-9.  Back to cited text no. 2
    
3.
Lookingbill DP, Spangler N, Sexton FM. Skin involvement as the presenting sign of internal carcinoma. A retrospective study of 7316 cancer patients. J Am Acad Dermatol 1990;22:19-26.  Back to cited text no. 3
    
4.
Calongos G, Ogino M, Kinuta T, Hori M, Mori T. Sister Mary Joseph nodule as a first manifestation of a metastatic ovarian cancer. Case Rep Obstet Gynecol 2016;2016:1087513.  Back to cited text no. 4
    
5.
Mayo WJ. Metastasis in cancer. Proc Staff Meet Mayo Clin 1928;3:327.  Back to cited text no. 5
    
6.
Girijala RL, Riahi RR, Cohen PR. Sister Mary Joseph nodule as a cutaneous manifestation of metastatic appendiceal adenocarcinoma: Case report and literature review. Cureus 2018;10:e2244.  Back to cited text no. 6
    
7.
Albano EA, Kanter J. Images in clinical medicine. Sister Mary Joseph's nodule. N Engl J Med 2005;352:1913.  Back to cited text no. 7
    
8.
Liu JW, Ma DL. An ominous sign from Sister Mary Joseph. Lancet 2018;392:776.  Back to cited text no. 8
    
9.
Prignano F, Lazzeri L, Massi D. Sister Mary Joseph node. QJM Int J Med 2017;110:473.  Back to cited text no. 9
    
10.
Handa U, Garg S, Mohan H. Fine-needle aspiration cytology of Sister Mary Joseph's (paraumbilical) nodules. Diagn Cytopathol 2008;36:348-50.  Back to cited text no. 10
    
11.
Cathro HP, Stoler MH. Expression of cytokeratins 7 and 20 in ovarian neoplasia. Am J Clin Pathol 2002;117:944-51.  Back to cited text no. 11
    
12.
Kriplani D, Patel MM. Immunohistochemistry: A diagnostic aid in differentiating primary epithelial ovarian tumors and tumors metastatic to the ovary. South Asian J Cancer 2013;2:254-8.  Back to cited text no. 12
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13.
Ahmed AA, Etemadmoghadam D, Temple J, Lynch AG, Riad M, Sharma R, et al. Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary. J Pathol 2010;221:49-56.  Back to cited text no. 13
    
14.
Oien DB, Chien J. TP53 mutations as a biomarker for high-grade serous ovarian cancer: Are we there yet? Transl Cancer Res 2016;5:S264-8.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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