Fine needle aspiration cytology of cervical lymph node involvement by ovarian serous borderline tumor
Longwen Chen MD, PhD 1, Kristina A Butler MD 2, Debra A Bell MD 3
1 Division of Anatomic Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA
2 Department of Obstetrics and Gynecology, Mayo Clinic Arizona, Phoenix, AZ, USA
3 Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA
|Date of Submission||21-Jan-2016|
|Date of Acceptance||26-Feb-2016|
|Date of Web Publication||27-Jul-2016|
Division of Anatomic Pathology, Mayo Clinic Arizona, Scottsdale, AZ
Source of Support: None, Conflict of Interest: None
Serous borderline tumor (SBT) involving a cervical lymph node is extremely rare. In addition, fine needle aspiration (FNA) cytology of the involved cervical lymph node shares tremendous morphologic similarity with other low-grade papillary carcinomas. Thus, it can be easily misdiagnosed as metastatic carcinoma. A 42-year-old female had a history of bilateral SBT and postbilateral salpingo-oophorectomy. She presented with left cervical lymphadenopathy 6 months later. FNA cytology showed a low-grade papillary neoplasm with psammoma bodies. Needle core biopsy along with immunostains was diagnostic of cervical lymph node involvement (LNI) of SBT. although extremely rare, cervical LNI can be found in patients with SBTs. FNA cytology, sometimes, is indistinguishable from metastatic papillary adenocarcinoma. Cell block or needle core biopsy is essential to make the correct diagnosis.
Keywords: Cervical lymph node, fine needle aspiration biopsy, ovarian serous borderline tumor
|How to cite this article:|
Chen L, Butler KA, Bell DA. Fine needle aspiration cytology of cervical lymph node involvement by ovarian serous borderline tumor. CytoJournal 2016;13:16
|How to cite this URL:|
Chen L, Butler KA, Bell DA. Fine needle aspiration cytology of cervical lymph node involvement by ovarian serous borderline tumor. CytoJournal [serial online] 2016 [cited 2017 Jul 26];13:16. Available from: http://www.cytojournal.com/text.asp?2016/13/1/16/187052
| » Introduction|| |
Serous borderline tumors (SBT) account for 10-15% of ovarian serous tumors.  They may occur at any age but are most common in the reproductive era. Most SBTs are Stage I.  SBT spread within the pelvis (Stage II) or spread to the abdomen or lymph nodes (Stage III) are not uncommon. ,, Rare Stage IV tumors (<1%) have been reported with cervical lymph node involvement (LNI).  Nevertheless, the overall 10-year survival of SBT is excellent, ranging from 65% (Stage II-Stage IV) to 98% (Stage I). ,,,,
Although rare, SBTs involving a cervical lymph node are sometimes encountered in the fine needle aspiration (FNA) cytology. However, the cytomorphology of cervical lymph node involved by SBT has not been well-characterized in cytology literature.
Here, we describe a case of FNA cytology of cervical LNI by SBT, presenting as cervical lymphadenopathy, 6 months following bilateral salpingo-oophorectomy of both ovaries.
| » Case Report|| |
A 42-year-old gravida 0 female experienced several months of pelvic pain and vaginal discharge at the end of 2014. Vaginal ultrasound revealed bilateral adnexal masses and her serum CA125 was elevated (429 U/mL). She subsequently underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, bilateral pelvic, and periaortic lymphadenectomy at an outside institution. The outside pathology, which was confirmed by two of the authors (LC and DAB) revealed bilateral ovarian SBT with noninvasive implants of the omentum and peritoneum. Two of the six bilateral pelvic lymph nodes were involved by SBT. The SBT did not show any micropapillary pattern or areas of microinvasion. The final stage for the SBT was stage IIIC.
Six months later, the patient serum CA 125 was 106 U/mL. A surveillance imaging (Positron emission tomography-computed tomography [PET CT]) revealed left cervical lymphadenopathy. Subsequent ultrasound of the thyroid revealed a small (5 mm) nodule with possible microcalcifications within the left mid pole. The possibility of metastatic thyroid carcinoma was raised. An ultrasound-guided FNA as well as needle core biopsy of the left neck level IV lymph node was performed.
Six cytology smear slides were prepared and subsequently stained with Papanicolaou (Pap) stain. The needle core biopsy was processed by paraffin-embedded block, and the slides were stained with H and E. The Pap-stained smear slides showed numerous papillary groups of epithelioid cells in a background of lymphoid cells [Figure 1]. Psammomatous calcifications were also noted. On high power magnification (×400), the epithelioid cells were intermediate to large as compared to the background lymphocytes but relatively uniform. The cells had a high nuclear-to-cytoplasmic ratio. The nuclei were predominantly oval and exhibited fine nuclear chromatin. Prominent nuclear grooves and irregular nuclear membrane were also observed [Figure 2]. Psammomatous calcifications were also noted [Figure 3]. Definite cytoplasmic intranuclear pseudoinclusions were not seen. Because of the papillary groups of epithelioid cells, the psammomatous calcification, and the nuclear grooves, the diagnosis of metastatic papillary thyroid carcinoma (PTC) was entertained. The needle core biopsy showed extensive deposits of tubular and papillary groups of tumor cells with psammomatous calcification in the background of lymphoid tissue [Figure 4]. The tumor cells were immunoreactive for estrogen receptor (ER) and WT-1 [Figure 5] and [Figure 6], whereas they were nonreactive for thyroid transcription factor-1 (TTF-1) and thyroglobulin. Therefore, the diagnosis of cervical lymph node involved by SBT was made.
|Figure 1: The Papanicolaou stain cytology smear slide shows numerous papillary groups of epithelioid cells in a background of lymphoid cells (×100)|
Click here to view
|Figure 2: The Papanicolaou stain cytology smear slide shows that the epithelioid cells were relatively uniform. The cells had a high nuclear-to-cytoplasmic ratio. The nuclei were predominantly oval and exhibited fine nuclear chromatin. Quite prominent nuclear grooves and irregular nuclear membrane were also noted (×400)|
Click here to view
|Figure 3: The Papanicolaou stain cytology smear slide shows several psammoma bodies associated with tumor cells (×400)|
Click here to view
|Figure 4: The needle core biopsy shows deposits of tubular and papillary groups of tumor cells with psammomatous calcification in the background of lymphoid tissue (H and E, ×200)|
Click here to view
|Figure 5: The tumor cells are immunoreactive with estrogen receptor (×200)|
Click here to view
|Figure 6: The tumor cells are immunoreactive (nuclear staining) with WT-1 (×200)|
Click here to view
The patient felt very well with no symptoms despite her abdomen and neck lymphadenopathy. Given the low-grade nature of her tumor, a rather conservative management plan including observation and hormonal treatment (aromatase inhibitor) was offered. A subsequent PET-CT found that the patient's cervical lymphadenopathy is stable.
| » Discussion|| |
LNI is present in 20-30% of patients with SBT, who undergo lymphadenectomy as part of staging. ,,, However, supradiaphragmatic LNI is extremely rare.  Cervical lymph node by SBT has only been described in the surgical pathology literature by few case reports.  To the best of our knowledge, the FNA cytology of cervical LNI by SBT has not been well-reported in cytology literature.
Here, we present this rare FNA cytology case of cervical lymph node involved by SBT. Due to a suspicious 5 mm thyroid nodule detected by ultrasonography, the diagnosis of metastatic thyroid carcinoma is raised clinically. The FNA cytology of this case shows many morphological features overlapping SBT and PTC, which include papillary clusters of epithelial cells, psammoma bodies, and nuclear grooves. Although psammoma bodies are highly characteristic, they are not pathognomonic of PTC and present in only a minority of cases in FNA cytology.  One of the major diagnostic features for PTC, cytoplasmic intranuclear pseudoinclusions,  is missing in our case. However, the cytological diagnosis of PTC is based on a plethora of morphological features rather than a single feature and the presence of cytoplasmic intranuclear pseudoinclusions is not specific for PTC. , Due to these overlapping features of SBT and PTC, a cell block or needle core biopsy along with immunohistochemical stains are essential to make the correct diagnosis. In this case, we select a panel of ER, TTF-1, thyroglobulin, and WT-1 to differentiate SBT from PTC, since most of the SBTs are positive for ER and WT-1, and they are negative for TTF-1 and thyroglobulin. , These results prove the importance of immunostains in the diagnosis of cervical lymph node involved by SBT.
Because of the low-grade appearance of the tumor cells, we do not consider the possibility of high-grade papillary serous carcinoma metastatic to cervical LN. Another diagnostic consideration is metastatic papillary adenocarcinoma of other sites. The low-power microscopic examination shows numerous papillary groups of epithelial cells. This finding certainly raises the possibility of papillary carcinoma other than PTC, such as lung papillary adenocarcinoma or papillary renal cell carcinoma (RCC). Papillary adenocarcinoma of the lung is composed of true papillae with fibrovascular cores and lined by epithelial cells with nuclear changes reminiscent of PTC.  In addition, both lung adenocarcinoma and PTC show the same staining positivity pattern with TTF-1. The immunoprofile of our case excludes the possibility of both tumors.
FNA cytology of type 1 papillary RCC often displays papillae lined by a single layer of uniform epithelial cells. Nuclear grooves, intranuclear pseudo-inclusions, and psammoma bodies may occur and can be indistinguishable from PTC. However, papillary RCC usually shows moderate amount of fine to vacuolated cytoplasm and foamy macrophages.  The immunoprofile of ER and WT-1 positivity also excludes the possibility of papillary RCC.
The correct diagnosis of cervical lymph node involved by SBT is paramount for the patient's clinical management. In our case, if the erroneous diagnosis of metastatic PTC was made, the patient would have a total thyroidectomy. Verbruggen et al. have described three cases of ovarian SBT involving cervical lymph nodes. The preliminary diagnosis of metastatic adenocarcinoma was made on all three cases and resulted in erroneous therapies in one case.  Thus, when FNA cytology of cervical lymph nodes showing features of possible papillary adenocarcinoma, it is recommended to include SBT in the differential diagnosis, especially when patients have a clinical history of SBT.
The clinical implication of lymph node involved by SBTs is also intriguing. Most studies have found that LNI is not an adverse prognostic factor independent of stage. ,,,,, However, McKenney et al. found that one pattern, >1 mm nodular confluent involvement without intervening lymphoid tissue, may be an adverse prognostic factor.  Furthermore, in about 80% of cases of SBT involving lymph nodes, peritoneal implants are also present requiring upstage. ,, Despite these conflicting data, the clinical management of patients with LNI is generally conservative due to the indolent behavior of SBT. ,, Cervical lymph node involved by SBT is extremely rare. In cases described by Verbruggen et al., all 3 patients remain free of disease after a follow-up period of 48-84 months. The study concludes that the prognosis of cervical lymph node involved by SBT differs significantly from that of adenocarcinoma of unknown primary; therefore, the correct diagnosis is critical to avoid ineffective treatment with chemotherapy. 
In summary, although rare, cervical LNI can be found in patients with SBT. FNA cytology of these positive lymph nodes, sometimes, is indistinguishable from metastatic papillary adenocarcinoma. Cell block or core biopsy along with immunocytochemical stains are essential to make the correct diagnosis.
| » Competing Interests Statement by all Authors|| |
The authors have no competing of interest to declare.
| » Authorship Statement by all Authors|| |
Each author (LC, KAB, and DAB) has participated sufficiently in the work and take public responsibility for appropriate portions of the content of this article.
| » Ethics Statement by all Authors|| |
The study subject has given her informed consent, and the information suitable to reveal the subject's identity is to be avoided.
(In alphabetic order)
| » List of Abbreviations|| |
ER - Estrogen Receptor
FNA - Fine Needle Aspiration
LNI - Lymph Node Involvement
Pap - Papanicolaou
PTC - Papillary Thyroid Carcinoma
PET-CT - Positron Emission Tomography-Computed Tomography
RCC - Renal Cell Carcinoma
SBT - Serous Borderline Tumor
TTF-1 - Thyroid Transcription Factor-1
| » References|| |
Bell DA, Longacre TA, Prat J, Kohn EC, Soslow RA, Ellenson LH, et al
. Serous borderline (low malignant potential, atypical proliferative) ovarian tumors: Workshop perspectives. Hum Pathol 2004;35:934-48.
Seidman JD, Kurman RJ. Ovarian serous borderline tumors: A critical review of the literature with emphasis on prognostic indicators. Hum Pathol 2000;31:539-57.
Shvartsman HS, Sun CC, Bodurka DC, Mahajan V, Crispens M, Lu KH, et al
. Comparison of the clinical behavior of newly diagnosed stages II-IV low-grade serous carcinoma of the ovary with that of serous ovarian tumors of low malignant potential that recur as low-grade serous carcinoma. Gynecol Oncol 2007;105:625-9.
Camatte S, Morice P, Atallah D, Pautier P, Lhommé C, Haie-Meder C, et al
. Lymph node disorders and prognostic value of nodal involvement in patients treated for a borderline ovarian tumor: An analysis of a series of 42 lymphadenectomies. J Am Coll Surg 2002;195:332-8.
McKenney JK, Balzer BL, Longacre TA. Lymph node involvement in ovarian serous tumors of low malignant potential (borderline tumors): Pathology, prognosis, and proposed classification. Am J Surg Pathol 2006;30:614-24.
Verbruggen MB, Verheijen RH, van de Goot FR, van Beurden M, Dorsman JC, van Diest PJ. Serous borderline tumor of the ovary presenting with cervical lymph node involvement: A report of 3 cases. Am J Surg Pathol 2006;30:739-43.
Malpica A, Deavers MT, Gershenson D, Tortolero-Luna G, Silva EG. Serous tumors involving extra-abdominal/extra-pelvic sites after the diagnosis of an ovarian serous neoplasm of low malignant potential. Am J Surg Pathol 2001;25:988-96.
Prat J, De Nictolis M. Serous borderline tumors of the ovary: A long-term follow-up study of 137 cases, including 18 with a micropapillary pattern and 20 with microinvasion. Am J Surg Pathol 2002;26:1111-28.
Trimble CL, Kosary C, Trimble EL. Long-term survival and patterns of care in women with ovarian tumors of low malignant potential. Gynecol Oncol 2002;86:34-7.
Gilks CB, Alkushi A, Yue JJ, Lanvin D, Ehlen TG, Miller DM. Advanced-stage serous borderline tumors of the ovary: A clinicopathological study of 49 cases. Int J Gynecol Pathol 2003;22:29-36.
Tan LK, Flynn SD, Carcangiu ML. Ovarian serous borderline tumors with lymph node involvement. Clinicopathologic and DNA content study of seven cases and review of the literature. Am J Surg Pathol 1994;18:904-12.
Kennedy AW, Hart WR. Ovarian papillary serous tumors of low malignant potential (serous borderline tumors). A long-term follow-up study, including patients with microinvasion, lymph node metastasis, and transformation to invasive serous carcinoma. Cancer 1996;78:278-86.
Djordjevic B, Malpica A. Lymph node involvement in ovarian serous tumors of low malignant potential: A clinicopathologic study of thirty-six cases. Am J Surg Pathol 2010;34:1-9.
Klinck GH, Winship T. Psammoma bodies and thyroid cancer. Cancer 1959;12:656-62.
Das DK. Intranuclear cytoplasmic inclusions in fine-needle aspiration smears of papillary thyroid carcinoma: A study of its morphological forms, association with nuclear grooves, and mode of formation. Diagn Cytopathol 2005;32:264-8.
Miller TR, Bottles K, Holly EA, Friend NF, Abele JS. A step-wise logistic regression analysis of papillary carcinoma of the thyroid. Acta Cytol 1986;30:285-93.
Lew W, Orell S, Henderson DW. Intranuclear vacuoles in nonpapillary carcinoma of the thyroid. A report of three cases. Acta Cytol 1984;28:581-6.
Bárcena C, Oliva E. WT1 expression in the female genital tract. Adv Anat Pathol 2011;18:454-65.
Escobar J, Klimowicz AC, Dean M, Chu P, Nation JG, Nelson GS, et al
. Quantification of ER/PR expression in ovarian low-grade serous carcinoma. Gynecol Oncol 2013;128:371-6.
Bellevicine C, Vigliar E, Malapelle U, Carelli E, Fiorelli A, Vicidomini G, et al
. Lung adenocarcinoma and its thyroid metastasis characterized on fine-needle aspirates by cytomorphology, immunocytochemistry, and next-generation sequencing. Diagn Cytopathol 2015;43:585-9.
Lim JC, Wojcik EM. Fine-needle aspiration cytology of papillary renal cell carcinoma: The association with concomitant secondary malignancies. Diagn Cytopathol 2006;34:797-800.
Longacre TA, McKenney JK, Tazelaar HD, Kempson RL, Hendrickson MR. Ovarian serous tumors of low malignant potential (borderline tumors): Outcome-based study of 276 patients with long-term (> or =5-year) follow-up. Am J Surg Pathol 2005;29:707-23.
Hannibal CG, Vang R, Junge J, Frederiksen K, Kjaerbye-Thygesen A, Andersen KK, et al
. A nationwide study of serous "borderline" ovarian tumors in Denmark 1978-2002: Centralized pathology review and overall survival compared with the general population. Gynecol Oncol 2014;134:267-73.
Silva EG, Gershenson DM, Malpica A, Deavers M. The recurrence and the overall survival rates of ovarian serous borderline neoplasms with noninvasive implants is time dependent. Am J Surg Pathol 2006;30:1367-71.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]