A rare case of extensive skeletal muscle metastases in adenocarcinoma cervix identified by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography scan.

Adenocarcinoma cervix is an uncommon histological subtype of carcinoma cervix; further incidence of skeletal muscle metastases is even rarer. We report the identification of extensive fluorodeoxyglucose (FDG) avid metastatic skeletal muscle deposits in a known case of adenocarcinoma cervix. The largest lesion representative of muscle deposit in the right deltoid was histopathologically confirmed to be metastatic poorly differentiated carcinoma. This report also serves to highlight the importance of (18)F-FDG positron emission tomography/computed tomography (CT) as compared to conventional imaging modalities such as CT and ultrasonography and comments better over the description of invasiveness as well as the extent of disease in carcinoma cervix.

INTRODUCTION

Cervical carcinoma is the most common malignancy in women in India and second only to breast cancer in women in worldwide data.[1] Direct local extension and lymphatic embolization are the routes of spread of cervical carcinoma. Hematogenous dissemination usually occurs with more advanced disease, poorly differentiated tumors, and aggressive cell types such as adenosquamous or neuroendocrine tumors.[2] Skeletal muscle metastases from cervical carcinoma are extremely rare, reported to be less than 1% of metastases of hematogenous origin of any cancer.[34] To our knowledge, from the existing literature search, only 11 cases of skeletal muscle metastases have been documented, of which ten have been from squamous cell carcinoma subtype of cervical cancer and one from the small cell carcinoma subtype.[34567891011121314]

We report an unusual case of adenocarcinoma cervix with extensive skeletal muscle metastases during staging work-up as detected by 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT).

CASE REPORT

A 48-year-old female presented with a history of decreased appetite, episodic pain in lower abdomen associated with mild grade fever and chest pain for 1 month duration. Clinical examination revealed a cachectic lady (weight loss undocumented, body mass index - 15.6 kg/m2) with decreased air entry on the left side of the chest. The lady was further investigated using contrast-enhanced CT scan (CECT chest and abdomen) which revealed the following findings: (a) Irregular nodular hypodense peripherally enhancing lesion in the cervix and right obturator internus muscle. Differential diagnoses? Abscesses? Neoplastic (b) bulky uterus with a small fundal fibroid. (c) Bilateral pleural effusion with a small suspicious pleural-based lesion and nodular thickening of interlobar fissures. Following the CT scan, a diagnostic pleural tap was done, which was negative for malignant cells. Therefore, the lesions in the lung were inferred to be of infective pathology and the patient was treated with injectable antibiotics for the same. Female was further subjected to per vaginal examination for clinical correlation with the imaging findings, which revealed a puckered and nodular anterior and posterior vaginal wall mucosa. A punch biopsy [Figure 1] was taken from the vaginal vault, which revealed a well-differentiated adenocarcinoma. There was no clinical suspicion of distant metastasis to skeletal muscles. Following this diagnosis, she was referred to our center for further management. Laboratory investigations were within normal limits. The patient underwent 18F-FDG PET/CT at our department for staging work-up [Figures 2,4-7]. The PET/CT scan revealed (a) an FDG avid ill-defined soft tissue thickening in the cervix and the upper part of vagina (b) multiple hypodense FDG avid muscle deposits in the following sites: Semispinalis capitis, bilateral biceps and triceps brachii, bilateral paraspinal muscles, bilateral deltoid, left trapezius, bilateral supraspinatus, bilateral infraspinatus, bilateral gluteal muscles, bilateral pyriformis, right obturator internus, and left rectus femoris with the largest lesion (metastatic deposit) noted within the deltoid (c) non-FDG avid pleural effusion in bilateral hemithorax (d) FDG avid multiple bone marrow deposits. Following the study, a clinical diagnosis of metastatic adenocarcinoma cervix Stage IVb (International Federation of Gynaecology and Obstetrics [FIGO]) was made. A fine needle aspiration cytology [Figure 3] from the representative focal deposit in the right deltoid revealed metastatic deposit of poorly differentiated carcinoma, thus confirming our findings. After the final staging work-up, the patient was started on systemic chemotherapy by the treating onco-physician.

Figure 1

H and E-stained punch biopsy slide of vaginal growth revealing morphological features of well-differentiated adenocarcinoma with diffuse mixed inflammatory cell infiltrate

Figure 2

Whole body positron emission tomography/computed tomography images: (a) Axial section showing hypermetabolic skeletal muscle deposits in both deltoid muscles. (b) Axial section showing multiple hypermetabolic skeletal muscle deposits. (c) Axial section showing a metabolically active soft tissue density lesion in cervix and upper part of vagina along with a hypermetabolic muscle deposit in right obturator internus. (d) Maximum intensity projection image in coronal section showing multiple focal muscle deposits and multiple bone marrow deposits

Figure 4

(a) Plain computed tomography image showing hypodense soft tissue density deposits within bilateral deltoid muscle. (b) Positron emission tomography/computed tomography image showing metabolically active soft tissue density deposits within bilateral deltoid muscle, right paraspinal and left trapezius muscle. (c) Positron emission tomography/computed tomography image showing metabolically active soft tissue density deposits in right deltoid muscle and bilateral supraspinatus muscle. (d) Positron emission tomography/computed tomography image showing metabolically active soft tissue density deposits in bilateral triceps muscle

Figure 7

Positron emission tomography/computed tomography image showing a metabolically active soft tissue density mass lesion in the cervix along with an fluorodeoxyglucose avid soft tissue density deposit in the right obturator internus muscle

Figure 3

Romanovsky-stained slide of fine needle aspiration cytology taken from the right deltoid muscle showing atypical cells in clusters having large hyperchromatic nuclei with high nuclear-cytoplasmic ratio, prominent nucleoli and irregular nuclear membrane, suggestive of metastatic deposits of poorly differentiated carcinoma

(a) Axial maximum intensity projection image showing increased tracer uptake in the region of bilateral triceps muscle. (b) Positron emission tomography/computed tomography image showing metabolically active soft tissue density deposits in bilateral infraspinatus muscle. (c) Axial maximum intensity projection image showing increased tracer uptake in the region of bilateral infraspinatus muscle. (d) Positron emission tomography/computed tomography image showing metabolically active soft tissue density deposits in left trapezius, bilateral deltoid and paraspinal muscles

Plain computed tomography image showing a soft tissue density mass lesion in the cervix along with a hypodense soft tissue density deposit in the right obturator internus muscle

DISCUSSION

We have reported an unusual case of adenocarcinoma cervix with extensive skeletal muscle metastases during staging work-up. Based on initial clinical examination and investigations (CECT thorax and abdomen and punch biopsy vaginal vault), the patient was staged as a case of adenocarcinoma cervix Stage IIIb (FIGO). However, based on the 18F-FDG whole body PET /CT done at our center, the disease was upstaged to Stage IVb (FIGO).

Skeletal muscle involvement from cervical carcinoma is a rare finding and is usually documented in the context of an advanced stage tumor [as reported in literature appended in Table 1]. There are various hypotheses for the rarity of skeletal metastasis. The likely reasons could be: (a) The constant movement of skeletal muscles, which represents a difficult condition for the implantation and growth of metastatic cells; (b) the local production of lactic acid, which would create an unfavorable environment for metastatic cell growth; (c) The inhibition of cell invasion by protease inhibitors located in the basement membrane; (d) The antitumor activity of lymphocytes and natural killer cells within the skeletal muscle; (e)In vivo evidences that skeletal muscle delivered peptidic factors may negatively influence the process of metastatic spread.[34]

Table 1

Characteristics of cervical cancer patients with skeletal muscle involvement, as reported in the literature

Our case was unusual for the fact that it was a case of multiple skeletal metastases from an uncommon histological subtype of cervical carcinoma. This case further reiterates the importance of PET/CT in staging and further management of the carcinoma cervix.

CONCLUSION

Skeletal muscle metastases from adenocarcinoma cervix are rare. However, the diagnosis of the same may alter disease staging, management, and prognosis. It can be solitary or multiple; therefore, FDG PET/CT has an added benefit of diagnosing advanced disease and extent of metastases by providing whole body scan information.

In the above-mentioned case report, F-18 FDG PET/CT gave information of multiple skeletal muscle deposits in clinically obscured metastases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.