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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 46  |  Issue : 1  |  Page : 50-54

When the metastatic tumor presents as a primary tumor: Gastric signet-ring cell carcinoma presenting as advanced cervical cancer with ovarian metastasis


Department of Obstetrics and Gynecology, De La Salle University Medical Center, Dasmarinas City, Cavite, Philippines

Date of Submission24-Jan-2022
Date of Acceptance24-Jan-2022
Date of Web Publication15-Apr-2022

Correspondence Address:
Angelito D L. Magno
Department of Obstetrics and Gynecology, De La Salle University Medical Center, Gov. D. Mangubat St. Avenue, Dasmarinas City, Cavite
Philippines
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pjog.pjog_9_22

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  Abstract 


Ovarian cancer is the second most common malignancy of the lower part of the female genital tract. Primary signet-ring cell carcinoma (SRCC) of the ovary is rare and is most commonly metastatic from a primary lesion. Discerning between primary and metastatic SRCC of the ovary or cervix may be difficult. SRCC of the cervix is also a rare type of cervical carcinoma, and just like in the ovary, it is usually metastatic from a primary gastric tumor. Presented here is a case of a 37-year-old nulligravid, who presented with an increase in abdominal girth with associated abdominal pain. The initial impression was ovarian new growth, probably malignant, and cervical mass, probably malignant. On laparotomy, intraoperative impression was cervical with ovarian malignant tumor, primary unknown versus double primary. Histopathology revealed metastatic adenocarcinoma, right ovary, cervical stroma, omentum, and umbilical mass with anterior abdominal mass. Peritoneal fluid was positive for malignant cells. Clinical correlation, further workup, and immunohistochemical stains for CK7, CK19, CK20, and CDX2 were recommended. All immunohistochemical results tested positive in tumor cells and were noted to be consistent with metastatic carcinoma of gastric versus pancreatic primary. Further workup was done, and the biopsy from the esophagogastroduodenoscopy revealed poorly differentiated adenocarcinoma with signet-ring features, antral mucosa.

Keywords: Cervical cancer, gastric signet, metastatic tumor


How to cite this article:
Flores MP, Magno AD. When the metastatic tumor presents as a primary tumor: Gastric signet-ring cell carcinoma presenting as advanced cervical cancer with ovarian metastasis. Philipp J Obstet Gynecol 2022;46:50-4

How to cite this URL:
Flores MP, Magno AD. When the metastatic tumor presents as a primary tumor: Gastric signet-ring cell carcinoma presenting as advanced cervical cancer with ovarian metastasis. Philipp J Obstet Gynecol [serial online] 2022 [cited 2022 May 27];46:50-4. Available from: https://www.pogsjournal.org/text.asp?2022/46/1/50/343238




  Introduction Top


Gastric cancer is the fifth most frequently diagnosed cancer, the fourth cause of cancer death worldwide is responsible for 9% of cancer deaths worldwide. Studies have shown that the incidence of signet-ring cell carcinoma (SRCC) subtype has been increasing. Diffuse-type gastric carcinoma, referred to SRCC, has poorly cohesive single cells with no gland formation. SRCC, it is more frequent in women than non-SRCC, occurring among younger patients of age ranging from 55 to 61 years.[1]

Ninety percentage of SRCC tumors arise from the stomach, breast, or colon, almost every organ is a potential primary site, but are still less frequently found in the breast, gallbladder, urinary bladder, and pancreas.[2] Gynecologic organs are not common metastatic sites for SRCC. Routes for implantation include hematogenous, spread, lymphatic spread, and surface implantation.[3] In one study, metastatic sites were focused on only a few sites, and only information about bone, brain, liver, lung, and distant lymph node metastasis was recorded in the Surveillance, Epidemiology, and End Results database.[4]

The objective of this article is to report a case of a metastatic tumor with the primary gynecologic presentation of cervical and ovarian mass and how the final diagnosis of gastric poorly differentiated adenocarcinoma with signet-ring features was reached. It aims to discuss the different diagnostic modalities that had to be partaken in order to reach the diagnosis.


  Case Report Top


This is a case of M.R.T, a 37-year-old nulligravid who consulted at a private attending physician due to increased abdominal girth and abdominal pain. Past medical is unremarkable and the patient has a family history of breast cancer from her maternal cousin. Personal and social history is noncontributory. She had menarche at 14 years old with a regular menstrual cycle lasting for 7 days consuming 6 moderately soaked pads per day with occasional dysmenorrhea. Her last normal menstrual period was June 11, 2020. She has had two sexual partners in her lifetime, her first sexual contact was at the age of 26. The patient has no history of sexually transmitted diseases. The patient never had a Pap smear done. She has no history of contraceptive use.

History revealed that the patient noted increased abdominal girth 2 months prior to admission, with no palpated masses. She as well noted hypogastric pain of about 7–8/10 intensity. There was no associated weight loss, vomiting, and change in bowel or urinary habits. She consulted at a private physician, a urinalysis and complete blood count was requested, which were noted to be unremarkable. The patient was then referred to an obstetrician–gynecologist and a transvaginal ultrasound was done revealing a normal sized anteverted uterus with intact endometrium, cervical mass, to consider carcinoma, ovarian new growth right with nonbenign sonologic features, with left ovarian cyst, with benign sonologic features, to consider endometrial cyst. The patient was subsequently referred to gyne oncology.

On further examination, the cervical mass was firm, nonfriable, and nonfungating with extension to the parametrium. Impression was not the usual epithelial cervical carcinoma but of stromal cancer or cervical lymphoma. A right adnexal mass was also palpated, which was thought to be a metastasis from a primary cervical cancer. An office cervical punch biopsy was attempted, but inadequate tissue sample was obtained due to the hard consistency of the cervical mass, which later revealed atypical cells suspicious of malignancy. Due to the inability to obtain histologic diagnosis of malignancy for the appropriate treatment, surgery was advised. Tumor markers such as HE4 (98.5 pmol/L (<70pmol/L) and CA125 (319.8 U/ml (0.00–35.00 U/ml) were determined.

On admission, she was ambulatory and coherent, with normal vital signs and systemic physical examination. There was no cervical and inguinal lymphadenopathy. A vague solid mass was palpable at the right lower quadrant. The external genitalia were normal with smooth vaginal. The cervix measured 4 cm × 4 cm and was converted to a hard, nonfriable, nonfungating mass extending to both parametria but not fixed to both pelvic sidewalls. A 5 cm × 5 cm solid nonmovable right adnexal mass was also palpated. The rest of the pelvic examination was unremarkable.

The admitting and preoperative impression was ovarian new growth, probably malignant with cervical mass, probably malignant, cervical, and ovarian lymphoma considered. The planned procedures were loop electrosurgery excision procedure (LEEP) of the cervical mass with exploratory laparotomy and peritoneal fluid cytology, with resection of right ovarian tumor.

On LEEP, a 2.0 × 0.5 hard cervical tissue was obtained. On laparotomy, there were approximately 1000 cc ascites noted. The uterus is fixed and densely adherent to the pelvic sidewalls. The parametria were fixed. The right ovary is converted to a homogenous, cream-tan doughy mass measuring 7.0 cm × 6.0 cm × 4.0 cm with grayish gel-like material noted upon cut section [Figure 1]. The left ovary was grossly normal but densely adherent to the left pelvic sidewall and uterus. The omentum was converted to a nodular, necrotic mass approximately 14.0 cm × 5.0 cm (caked omentum). Part of the sigmoid was densely adherent to the left pelvic sidewall and uterus. There were two nodular necrotic firm masses at the anterior abdominal wall and umbilical peritoneum measuring 4 cm and 1 cm, respectively. Tumor debulking with partial omentectomy, right salpingo-oophorectomy, and resection of anterior abdominal wall and umbilical mass were done. Due to re-accumulation of ascites during surgery, a Jackson-Pratt drain was inserted. The estimated blood loss was around 500 cc.
Figure 1: The right ovary measures 6.0 cm x 6.0 cm x 4.0 cm and weighs 100g. The external surface is doughy, smooth, slightly lobulated, and pale to cream-tan in color. Cut sections of the ovary show a cream-tan surface with a cream-white solid focus that measures 3.0 cm widest dimension and multiple cystic structures that measure 0.3 cm to 0.6 cm in widest diameter

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Histopathologic evaluation of the specimen revealed metastatic adenocarcinoma, right ovary [Figure 2], cervical stroma, omentum, umbilical mass, and anterior abdominal wall mass. Further evaluation of immunohistochemical stains for CK7, CK19, CK20, and CDX2 tested positive in tumor cells [[Figure 3] and [Figure 4] respectively] and was noted to be consistent with metastatic carcinoma of gastric versus pancreatic primary.
Figure 2: Histology of the ovary: Microscopically, it shows a malignant neoplasm disposed in sheets and occasional abortive and well-formed glands infiltrating the ovarian stroma with accompanying desmoplasia. The cells are medium to large in size with scant to moderate amount of amphophilic vacuolated or clear cytoplasm and have moderately pleomorphic, hyperchromatic or vesicular nuclei with fine to coarse chromatin pattern and occasional visible nucleoli. Few mitotic figures are noted as seen pointed by red arrows. Mucinous material is observed in some of the glands. Several cells with abundant amount of intracytoplasmic mucin and eccentrically located compressed nuclei (signet-ring cells as seen pointed by yellow arrows) are seen primarily in the ovary

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Figure 3: CK7: Positive in tumor cells

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Figure 4: CK19: Positive in tumor cells

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The patient stayed for 3 days postoperatively at the hospital with stable vital signs and good recovery and was advised for respective follow-up.

In the search of the primary tumor, gastrointestinal (GI) endoscopy and whole abdominal computed tomography (CT) Scan were requested. Contrast-enhanced whole abdominal CT scan showed the absence of pancreatic mass. The patient underwent gastric endoscopy and revealed a solitary gastric ulcer in the distal body of the antrum [Figure 5]. Gastric fluid analysis through a rapid urease was done as well and tested positive for Helicobacter Pylori. Biopsy of the ulcer was done and later revealed poorly differentiated adenocarcinoma with signet-ring features, antral mucosa [Figure 6]. The patient was then referred to a medical oncologist for appropriate cancer treatment.
Figure 5: The stomach had good distensibility and contractility. A 3 cm ulcer with clean base, irregular and nodular borders was seen at the lesser curve, distal body extending into the antrum

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Figure 6: Histopathology of the gastric ulcer: Microscopically, sections underneath the ulcerated, inflamed, and fibrotic mucosa show malignant neoplasm disposed singly in clusters, cords, trabeculae, and sheets invading the mucosa. The cells are characterized by medium to large round, ovoid, crescentic hyperchromatic or vesicular centrally or eccentrically located (signet-ring cells as seen pointed by yellow arrows) nuclei. Cytoplasm is adequate to abundant, amphophilic or basophilic vacuolated or clear. Few mitotic figures are seen

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  Case Discussion Top


Gastric cancer is the fifth most frequently diagnosed cancer and the fourth cause of cancer death worldwide, responsible for about 9% of cancer deaths. Studies have shown that the incidence of SRCC subtype has been increasing. Diffuse-type gastric carcinoma, referred to SRCC, has the presence of signet-ring cells and has poorly cohesive single cells with no gland formation. SRCC is more frequent in women as compared to non-SRCC. It occurs among younger patients of age ranging from 55 to 61 years. SRCC s are further classified into two types, undifferentiated type and diffuse type. As WHO describes it, SRCC is a weakly cohesive type of gastric carcinoma that has tumor cells with prominent cytoplasmic mucin and a crescent-shaped nucleus eccentrically located.[1]

It commonly arises in the stomach but has also been reported in the colon, breast, prostate, and rectum. Common metastatic sites are liver, lung, bone, and lymphatics; colonic metastasis is rare.[5] Gynecologic organs are not common metastatic sites for SRCC.[3]

Primary SRCC of the ovary is rare. Krukenberg tumors are infrequent metastatic tumors of the ovaries with presence of mucin-producing neoplastic SRCC. They comprise 1%–2% of all ovarian tumors occurring approximately 0.16 per 100,000/year.[6] These tumors do not originate in the ovary but are metastases from a primary malignancy elsewhere, the GI tract being the most common site. Routes of metastasis to the ovary include hematogenous spread, lymphatic spread, and surface implantation. Patients usually present with abdominal pain and distension.[3] This was noted in our patient.

Primary SRCC of the cervix is extremely rare.[7] Most malignant lesions with signet-ring cell morphology are metastatic. The uterus, corpus, and cervix included area rare metastatic site. The mechanisms of metastasis from gastric cancer are not clearly understood, but mostly, it is attributed to local lymphatic spread from a preceding ovarian metastasis and if the ovaries are not involved, hematological spread. Patients usually present with abnormal bleeding or postcoital bleeding.[3] Both were not present in our patient.

In this case, the primary presentation of the patient was gynecologic having cervical and ovarian masses rather than GI ones; hence, a GI diagnosis was not considered initially. Diagnostics played a major role in the case. The primary origin could not be concluded until further diagnostics were done.

The workup for malignancies and detailed investigations fail to reveal a primary site in about 3%–5% of metastatic tumors. Most SRCCs occur in the GI tract; when there is peritoneal carcinomatosis or omental caking on CT imaging, further diagnostics involving cytologic analysis of peritoneal fluid (immunohistochemical may lead to the origin), imaging, colonoscopy, and upper endoscopy are considered.[2] Most of these were done in our case postoperatively.

Preoperatively, tumor markers as initially taken (CA 125 and HE4) were both elevated, which can be an indication that the ovarian tumor is malignant, thus our primary consideration, but when histopathology of the all specimens taken postoperatively revealed the presence of signet cells, the question to be determined now was “Where did it originate?” Immunohistochemical stains for CK7, CK19, CK20, and CDX2 tested positive in tumor cells. This further narrowed the investigation to our origin, but it still was not conclusive because, in our case, she tested positive for all stains. CK20 is positive in the GI epithelium, urothelium, and in Merkel cells while CK7 is positive in the lung, ovary, endometrium, and breast cancers, but not in tumors of the lower GI tract. CDX2 turns out positive in colorectal carcinoma. When CK20 is positive and CK7 is negative, it usually indicates a colorectal primary in 17 of 21 cases (81%) in one study. In the same study when CK20 and CK7 are both positive, it usually indicates pancreaticobiliary origin in 11 of 14 cases (79%). More than two-third of cases of gastric adenocarcinomas also express CDX2.[8] CK19, on the other hand, is high in colorectal SRCCs.

Imaging studies may be of use to scan any other possible pathology and possibly find our primary site. These studies used for diagnosis and staging include endoscopic ultrasonography, CT, and positron-emission tomography (PET)-CT scan. Double-contrast barium upper GI examination is also considered as it has a 90%–95% sensitivity which is comparable to endoscopy. CT is ideally used preoperatively to note the stage and spread of a gastric carcinoma. In our case, since initially, a gynecologic pathology was considered, only a transvaginal ultrasound was done.

Abdominal CT scan was only done postoperatively and not absence of pancreatic mass excluding one of the possible organs of origin. Gastric wall thickening with mild luminal narrowing was also noted in the CT scan.

Magnetic resonance imaging and PET CT scans may be helpful in finding the primary organ but were not done due to the restrictive cost of these studies.

The role of H. Pylori in SRCC is controversial because it is a more common risk factor in non-SRCC as it is the cause of chronic gastritis which is associated in most cases of gastric cancer. Since H. Pylori has been better controlled, H. Pylori-negative gastric cancers have been identified which are seen in gastric adenocarcinoma thus the reason for questioning the role of H. Pylori.[9] Nevertheless, according to WHO, they have certified H. pylori as a carcinogen in 1994. With this being said, the H. Pylori infection in our patient still attributed to her gastritis, eventually leading to gastric cancer.

H. Pylori infection was assessed along with biopsies of the gastric mucosa taken on our last and final diagnostic modality. The esophagogastroduodenoscopy (EGD) was done to evaluate gastric wall and lymph node involvement, and through this, we were able to confirm our primary site. EGD has a diagnostic accuracy of 95% obtaining tissue from a suspected lesion.

Biopsies were taken from the ulcerated lesion and low and behold, the results revealed poorly differentiated adenocarcinoma with signet-ring features, antral mucosa.


  Summary and Conclusion Top


Discerning between primary and metastatic SRCC of the ovary or cervix may be difficult. A thorough clinical history and physical examination paired with diagnostic modalities may be able to aid in arriving at the correct diagnosis. In our case, diagnostic modalities such as immunohistochemistry and GI endoscopy were the main determinant factors to arrive at our final diagnosis. Initially, history and physical examination may lead you to a different diagnosis, but with further workup, it shows that the diagnosis could be narrowed down to the primary source.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Machlowska J, Puculeck M, Sitarz M, Terlecki P, Maciejewski R, Sitarz R. State of the art for gastric signet ring cell carcinoma: From classification, prognosis, and genomic characteristics to specified treatments. Cancer Manag Res 2019;11:2151-61.  Back to cited text no. 1
    
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Al-Taee A, Almukhtar R, Lai J, Jallad B. Metastatic signet ring cell carcinoma of unknown primary origin: A case report and review of the literature. Ann Transl Med 2016;4:283.  Back to cited text no. 2
    
3.
Matsushita H, Watanabe K, Wakatsuki A. Metastatic gastric cancer to the female genital tract. Mol Clin Oncol 2016;5:495-9.  Back to cited text no. 3
    
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Wu J, Fang D, Man D, Wu W, Wang Q, Li Y, et al. Clinical correlates and prognostic value of different metastatic sites in gastric and colorectal signet ring cell carcinoma. Engineering 2020;6:1028-34.  Back to cited text no. 4
    
5.
Winter M, Dokmak A, Marnory Z, Sinagar S, Levy A. Metastatic gastric signet ring cell carcinoma mimicking crohn's disease. ACG Case Rep J 2018;5:e36.  Back to cited text no. 5
    
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Spinelli C, Liloia C, Piscioneri J, Ugolini C, Strambi S. An unusual evolution of krukenberg tumour: A case report. J Clin Diagn Res 2016;10:PD07-11.  Back to cited text no. 6
    
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Cracchiolo B, Kuhn T, Heller D. Primary signet ring cell adenocarcinoma of the uterine cervix – A rare neoplasm that raises the question of metastasis to the cervix. Gynecol Oncol Rep 2016;16:9-10.  Back to cited text no. 7
    
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Selves J, Long-Mira E, Mathieu MC, Rochaix P, Ilié M. Immunohistochemistry for diagnosis of metastatic carcinomas of unknown primary site. Cancers (Basel) 2018;10:108.  Back to cited text no. 8
    
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Pernot S, Voron T, Perkins G, Lagorce-Pages C, Berger A, Taieb J. Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge. World J Gastroenterol 2015;21:11428-38.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]



 

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