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Small Cell Neuroendocrine Tumor of the Cervix

Short summary

36-year-old otherwise healthy female underwent routine tests that found atypical cells in Pap smear. Her cervix was biopsied, and found poorly differentiated neuroendocrine carcinoma. The findings of the PET-FDG test showed pathological absorption of FDG as a primary tumor of the cervix, towards the left side of the body. Moreover, evidence is seen of nodal metastatic spread in the retroperitoneum and pelvis. In the expert's opinion the patient has locally extensive small cell neuroendocrine carcinoma of the cervix with extensive pelvic and PA adenopathy. The prognosis for this type of lesion is extremely poor. Nevertheless it is reasonable to try neoadjuvant chemotherapy, followed by RT or hysterectomy.

Patient's questions

The patient asks about the diagnosis, prognosis and treatment options.


Medical Background

Age: 36
Gender Female

Current Complaint:
The patient is a 36 year old female. She is married with no children, and is generally healthy. She is not currently taking any medication, has no known sensitivities to any medication, and has never undergone surgery in the past.
Family history: Diabetic mother.
Normal menstrual cycle. Approximately 1 year ago, the patient underwent an abortion at week 16 of pregnancy, due to fetal abnormalities.
Routine tests found atypical cells in Pap smear.
Cervix was biopsied, and found CX POORLY DIFF NEUROENDOCRINE CA.
Tests found the patient to be in a good general state.
Belly was tender, groin was normal.
PS+PV – found on outer labia, diameter about 3cm, papillary.
Not spread to vagina: Parametrium normal.
Findings were explained, as were treatment options (surgery, chemotherapy, radiation), including options to preserve fertility.

Urgent PET CT is required, to evaluate these findings.

Report – Pathology test results
Clinical details and Diagnosis
36 year old with suspected cervical cancer
General Comments:
Copy of results sent to Israel National Cancer Registry, Jerusalem


Sample Type: Biopsy
Sample Location: Cervix Uteri
Material Sample: Tissue

Macroscopic Description
The material arrived in a container bearing the patient’s name, in formalin, matching the name on the order forms.
Three (3) samples, each approximately 0.6cm..

Microscopic Description:
Endocervical samples, coated with columnar epithelium. In stroma, diffuse area of small to medium sized cells with little cytoplasm, grainy, with a neuroendocrine appearance. Many mitoses seen. Lesion was accompanied by dense lymphocytic infiltration. Immunohistochemical staining showed the cells positive for NSE, SYN, CHR, and 90% positive for Ki67 (proliferative index).
Negative CK MNF116, CK5/6, CK18, EMA staining.

In Summary: The patient is suffering from a poorly differentiated neuroendocrine carcinoma. Size of the cells is small to medium.

Cervical Biopsy
Poorly Differentiated Neuroendocrine Carcinoma

Tests Undergone:
Date of Test  06.09             
Description of Service - PET-FDG mapping, glucose marked

Disease History
Tumor of the cervix with poor differentiation, with neuroendocrine characteristics.

List of Questions

Tests and Results - Description
Whole body PET FDG test was done, to mid-thigh level. The test was done with Discovery LS and combines a PET and CT, mapping simultaneously with FDG and CT sections.

Telebrix was given to demonstrate the intestinal loops while mapping with CT.

Pathological absorption of FDG is present, showing hypodense lesions of diameter 1.7cm on the left of the posterior aspect of the cervix. This lesion is very similar to the primary tumor. This lesion is not well differentiated from the rectum.
Increased, though not overly large absorption was seen in the uterine cavity, which appears hypodense. This finding is not necessarily a tumor, and may be a hydrometra.

Pathological absorption present in lymph nodes in the retroperitoneum and in the pelvis. The cranial node shows over-absorption is at L2 level, by the superior mesenteric, diameter 1mm on the short axis. The more caudal , the more absorption at the lymph nodes, with diameters up to 1.1cm at the short axis, joint internal iliac nodal chain on the right, and a greater number on the left, up to a diameter of 1.1cm, in the internal iliac chain up to diameter 1.1cm, at the bifurcation of the iliac blood vessels on the left, with dimensions of 1.4*1.5cm, and in the large nodes of the external iliac nodal chain on the left, the largest one has dimensions of 2.9*2.5cm.

No pathological absorption was demonstrated to prove metastatic spread with the PET scan to the lung area, liver, spleen, adrenals and skeleton.

In Summary:
The findings of the test showed pathological absorption of FDG as a primary tumor of the cervix, towards the left side of the body. Moreover, evidence is seen of nodal metastatic spread in the retroperitoneum and pelvis, mainly on the left.


Medical opinion

It is difficult to render a reliable opinion with the scant information offered. The file I received had no description of the patients’ physical examination and I found the language in the PET report a bit difficult to interpret. However, if I understand correctly, she has a locally extensive small cell neuroendocrine carcinoma of the cervix with extensive pelvic and PA adenopathy but as yet no evidence of hematogenous metastases. I wish I had a good answer for you. The prognosis for this type of lesion is extremely poor and, as yet, I know of no one who has found any reasonably successful treatment approach. It is my impression that the outcome is much worse than small cell carcinoma of the lung although many practitioners try to extrapolate from the lung experience to design treatment regimens for these patients. However, despite the similarity of histology to small cell of the lung, there is little evidence that treatment responses to chemo (and particularly curability) are similar.

It is not unreasonable to try some neoadjuvant chemotherapy, in view of the extensive lymphadenopathy. However, about 10 years ago we had a protocol for neoadjuvant cisplatin, adria, etoposide followed by RT or hysterectomy depending on the stage. With follow-up, there were no survivors among patients who had more than Ib1 disease. Pelvic recurrence was not a big problem in pts who had locoregional RT. However, marginal recurrences were frequent (above the field in PANs or below in the distal vagina). Most patients went on fairly quickly to develop hematogenous metastases as well. Brain mets only occurred in pts who had lung disease.

If the pt had only pelvic disease, I would argue for pelvic RT early because local progression is likely with chemo only. We usually treat with concurrent chemo-RT using platinum followed by 4-6 cycles of chemo (we always discuss relative merits of carbo/taxol vs. cis/etoposide); however, there are really few data to guide decision. I agree that extended fields could compromise ability to give subsequent chemotherapy so it is reasonable to start with some chemo but I would follow response very closely because these seem to progress fairly quickly despite combination chemotherapy.

A number of groups are exploring use of biologic response modifiers in patients with metastatic/recurrent disease but there are few data so far to justify adjuvant use.