Non-Hodgkin's lymphoma: A rare diagnosis on cervicovaginal cytology.

Cervicovaginal smear screening is well known to reduce morbidity and mortality rates of invasive cervical carcinoma. Herein, we report a case of 56-year-old woman whose cervicovaginal smear was found to consist of malignant cells characterized by high nuclear/cytoplasmic ratio, scant rim of cytoplasm, coarsely granular nuclear chromatin and irregular nuclear membrane that were all reminiscent of a malignant lymphoma. Histopathological examination of the hysterectomy and unilateral adnexectomy specimen confirmed the presence of a diffuse large B-cell non Hodgkin's lymphoma involving the cervix, endometrium, myometrium, serosa and the right ovary.

Introduction

Malignant lymphomas (ML) are among the well-known neoplasms generally involving the reticuloendothelial system.[1] Non-Hodgkin's lymphoma (NHL) arising from extranodal organs including female genital tract is an extremely rare entity.[23] Accordingly, only 0.5% of the extranodal lymphomas involve uterine cervix and corpus.[4] However, in the setting of a ML of the female genital tract, cervicovaginal cytology usually appears to be non-diagnostic due to the predominant subepithelial involvement by this tumor unless the mucosal surface undergoes ulceration with consequent spillover of malignant cells throughout the genital tract.[1] The present case report describes a postmenopausal patient with a NHL of the genital tract initially diagnosed through examination of the cervicovaginal smear.

Case Report

A 56-year-old postmenopausal woman (gravida 3, para1) was admitted to our gynecology clinic for a routine check-up. On pelvic examination, cervix was found to be enlarged, firm and hypervascular. A right adnexal mass was also grossly palpable. The microscopic examination of Papanicolaou stained cervicovaginal smear demonstrated the presence of a monomorphic population of malignant cells along with squamous and acute inflammatory cells [Figure 1]. These malignant cells were found to have an increased nuclear/cytoplasmic ratio, scant rim of cytoplasm and coarsely granular nuclear chromatin with irregular nuclear membranes that were reminiscent of a ML [Figure 2]. Thereafter, the patient underwent abdominal hysterectomy, unilateral salpingo-oophorectomy and pelvic lymphadenectomy. Histopathological examination of the excised specimen confirmed the invasion of the cervix, endometrium, myometrium, serosa and the right ovary, by a diffuse large B-cell NHL characterized by the diffuse infiltration of the malignant monomorphic cells with large, round to ovoid irregular nuclei and scanty cytoplasm. Of note, these cells were immunohistochemically positive for LCA, vimentin, CD 20, CD 30, Bcl 6, Bcl 2. Ki-67 index was found to be 80%. After the operation, the adjunctive examination of the bone marrow (BM) biopsy demonstrated that it was unaffected by the lymphoma infiltration.

Figure 1

Microscopy of the cervicovaginal smear demonstrating large malignant lymphoid cells among mature squamous cells (Pap stain, ×200)

Figure 2

Microscopy of the cervicovaginal smear demonstrating atypical lymphoid cells of variable size with irregular nuclear membranes, clumped chromatin and prominent nucleoli (Pap stain, ×400)

Discussion

ML of the female genital tract is an extremely rare entity. The age range at presentation is generally wide (20 to 80 years) with the median age ranging from 40 to 59 years. Histopathologically, large B-cell lymphoma has been the most frequently encountered type. Among the female genital tract organs, cervix is generally considered as the primary predilection site, and in the setting of gross cervical involvement, patients may exclusively present with cervical enlargement on pelvic examination. These tumors are characterized by the preferential infiltration of the stroma and the presence of a well-preserved epithelial lining explaining the negative results of the cervicovaginal smear examination in the relatively early stages of the disease course. The diagnostic features on cervicovaginal cytology are the presence of monomorphic cell population, high nuclear/cytoplasmic ratio, scant rim of cytoplasm, coarsely granular nuclear chromatin with chromatin clumping and the presence of prominent nucleoli.[1] Follicular or chronic cervicitis, small cell carcinoma, endometrial stromal sarcoma and granulocytic sarcoma should be considered among the differential diagnosis of this entity. In follicular or chronic cervicitis, numerous plasma cells and a polymorphous infiltrate of mature and immature lymphocytes generally forming lymphoid follicles are the frequently encountered findings in contrast to ML. Small cell carcinoma is characterized by the presence of tiny malignant cells harboring cloudy, opaque nuclei and small or absent nucleoli whereas the nuclei of malignant lymphoid cells typically demonstrate a more variation in size, shape and have prominent, sometimes multiple nucleoli. More importantly, the presence of nuclear molding in small cell carcinoma is the most striking feature in the differentiation of these entities. Endometrial stromal sarcoma, another differential diagnosis, is also characterized by small, mostly rounded malignant cells with discernible nucleoli and occasional comet forms and a tumor diathesis.[5] Granulocytic sarcoma is also another differential diagnosis that has a very poor prognosis in general.[6] This tumor is primarily composed of immature myeloid elements, and generally develops during the course of acute or chronic myeloid leukemia (AML or CML).[6] Microscopically, it consists of dyscohesive, medium to large cells with granular cytoplasm, reniform, ovoid nuclei and one or more nucleoli.[6]

In conclusion, NHL of the female genital tract is a rarely encountered entity that is extremely difficult to diagnose through examination of the cervicovaginal smear. The present case may be considered interesting because of its rarity and the way it was initially diagnosed. The cytopathologists dealing with gynecological specimens should keep this rare entity in mind while evaluating cervicovaginal smears.