With the improved diagnostic techniques of cancers patients, sophisticated treatment, increased survival, and life expectancy; the higher frequency of multiple primary malignant neoplasms are noticed [8].
Multiple primaries are defined as two or more unrelated primary malignant tumors of distinct histology and occur in the body at the same time or one after another. Synchronous primaries diagnosed in an interval of fewer than 6 months. Risk of developing an additional primary malignancy is varying because of the variable evaluation period and the inclusion criteria [5].
PET/CT is superior to conventional imaging for staging and restaging of most cancers. CT component provides the anatomical framework within which the biology of cancer can be visualized by PET. This powerful combination is a well-established tool in diagnostic work up of cancer patients [9].
In the current study, with the use of PET/CT image-guided biopsy, sensitivity for diagnosing additional primary malignancy is 95.23% (20/21), the PPV was 68.97% (20/29), and the false-positive rate was 31% (9/29) in concordance to study of Haoping Xu et al. [6] who had showed nearly the same sensitivity of 95.24% and higher PPV of 74.07%.
The detection rate in this study (3.26%) in relatively in concordance to Ali et al. [10], who had shown similar detection rate 13 out of 273 patients (4.76%) with the lower PPV of 56.5% and sensitivity of 89.2% and discordance to Servente et al. [11] who showed less detection rate (1.2%, 49/4086) and Tibana and Lee [3, 12] who had shown lesser detection rate (1.1).
In the current study, the most frequent primary neoplasm were lungs (n = 3) followed by breast (n = 2) and colon (n = 2) in discordance to study of Servente et al. [11] who founded the most common index tumors: breast (n = 27), lung (n = 27), and colorectal (n = 20) and study carried by Ishimori et al. [13] who found the foremost known primary tumors included lung (28.6%), colon or rectum (12.4%), and head or neck (12.1%).
Multiple primaries in patients with lung cancer are related to smoking, no association with radiotherapy [14], highest in small cell lung cancer (SCLC), squamous cell carcinoma, and fewer in adenocarcinoma. The most common second cancers are in the lung (adenocarcinoma < SCC < SCLC), colorectal, and bladder cancers [15].
Various factors contribute to the occurrence of multiple primaries in breast cancer; hormonal treatment of primary breast cancer (esp. Tamoxifen therapy) that increases the risk for endometrial, gastric, colon, and ovarian cancers [16]. Genetic factors (e.g., BRCA1, BRCA2) and obesity may increase the hazard for a second breast or ovarian cancer. Hereditary factors increase the risk gastric cancer and lobular breast cancer. Premenopausal increases risk of second breast, endometrial or ovarian cancer. Radiotherapy and chemotherapy increase the risk for a secondary primary in breast cancer, thyroid cancer, bone, connective tissue, and lung [17].
Multiple primaries in lymphoma
Radiation therapy has an increased risk for breast, lung, thyroid, and colorectal cancers. Chemotherapy is associated with an increased risk for leukaemias and lung, gastrointestinal or bladder cancer, soft tissue, and bone sarcomas.
In this study, the foremost common location of the second primary tumor was colon (n = 5) and lung (n = 5) in concordance to Servente et al. [11] who histologically confirmed second primary in colon (n = 18), lung (n = 6), breast (n = 6), and in discordance to study of Tibana et al. [3] who found most common sites of the additional malignancies were the lung (n = 4), kidney (n = 3), and prostate (n = 2).
There were 28 false-positive findings in the study of to Servente et al. [11] compared to the result of this study, in which only 9 false-positive findings detected.
Additional primary malignancy is suspected when abnormal FDG uptake in unusual site of metastasis or not follow the usual sequence of metastasis. For example, in breast cancer patients, an additional primary lung cancer is considered when an isolated pulmonary lesion is found in the absence of usual sequence of metastasis (axillary LNs, hepatic, or bone lesions), in addition, lung metastasis is rounded in appearance with relatively smooth margins, while a primary pulmonary malignancy appears spiculated or ground glass in appearance [17]. The usual sequence of metastasis in non-small cell lung cancer follows this orders LNs, adrenal glands, liver, bone, and brain [9]. The most common site of metastasis in squamous cell carcinoma of the head and neck is lung [8].
Synchronous malignancies within the upper digestive and respiratory tract related to the carcinogenic effects of alcohol and tobacco [18].
In spite the fact that false-positives can occur with FDG PET/CT, the predominance of true-positives cannot be belittled. Extra primary malignancies identified by PET/CT increases the probability of remedy if such malignancies are treated promptly and forcefully.
Limitations of the study
Limited sample size as the study conducted in single center, uncertain as to whether study patients were representative of all target population.
Selection bias
Study concerned with positive lesions in PET/CT, Negative cases could not attract attention to follow up and take biopsy to validate negative cases.
Study design
While prospective study allows comparing the independent roles of PET, CT components, unfortunately, this study is retrospective.
The study in concerned with additional malignancy whatever the primary, this makes it difficult to analyze link between the different primaries in full details, but in brief.