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 Table of Contents  
Year : 2015  |  Volume : 22  |  Issue : 4  |  Page : 233-236

Spectrum of second primary malignant neoplasms in central india: case series from a tertiary care centre

1 From the Department of Surgical Oncology, Sri Aurobindo Medical College and PG Institute, Indore, Madhya Pradesh, India
2 From the Department of Pathology, Sri Aurobindo Medical College and PG Institute, Indore, Madhya Pradesh, India

Date of Web Publication14-Jan-2016

Correspondence Address:
Suvadip Chakrabarti
From the Department of Surgical Oncology, Sri Aurobindo Medical College and PG Institute, Indore, Madhya Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1117-1936.173975

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Background: Cancer survivors are at an increased risk for developing second cancers than the general population. In recent times detection of a new second primary following the index primary has increased due to refinement of existing diagnostic tools and development of newer modalities of diagnosis combined with better understanding of patterns of inheritance, risk factors and environmental influences. Today with improvement in Cancer management the average lifespan of cancer survivors have increased along with the increase in detection of both synchronous and metachronous malignancy with increase in disease free survival. With the improved cancer survival, second primary malignancy has become an important issue among cancer survivors and an increased burden on the treating oncologists and health care system.
Aims and Objective: To report the trends of second malignancy in a tertiary care centre in Central India with review of relevant literature.
Methods: A hospital based retrospective collection of data of patients diagnosed with second primary malignancy based on Warren and Gates Criteria (1932) over 2 years in the Department of Surgical Oncology of a tertiary care centre in Central India.
Conclusion: Secondary primary malignancy needs to be separated from metastasis as the latter implies progression in disease and portends poor survival. Operable synchronous secondary primary malignancy can be tackled in the same sitting thereby reducing the load on the overburdened healthcare system in India. Increase in awareness of secondary primary malignancy leads to better chances of detection management and hence chances of improved survival.

Keywords: Dual malignancy, metachronous, second primary malignancy, synchronous

How to cite this article:
Chakrabarti S, Chakrabarti PR, Desai SM, Agarwal D, Mehta DY, Somanath S. Spectrum of second primary malignant neoplasms in central india: case series from a tertiary care centre. Niger Postgrad Med J 2015;22:233-6

How to cite this URL:
Chakrabarti S, Chakrabarti PR, Desai SM, Agarwal D, Mehta DY, Somanath S. Spectrum of second primary malignant neoplasms in central india: case series from a tertiary care centre. Niger Postgrad Med J [serial online] 2015 [cited 2022 Dec 6];22:233-6. Available from: https://www.npmj.org/text.asp?2015/22/4/233/173975

  Introduction Top

Billroth was the first to report dual malignancy in 1889. [1] Reported incidence of the second primary in a cancer patient is about 10%. [2] Studies have reported relative risks of second primary cancers ranging from 1.08 to 1.3. [3] Second primary malignancy (SPM) is a second malignancy arising de novo in a patient diagnosed with cancer. However, SPM are often missed during follow-up and are detected at the symptomatic state by the patient. [4] The paucity of awareness about SPM has also prevented the formulation of population-based screening protocol. [5],[6] According to Warren and Gates Criteria (1932) for diagnosis of SPM both tumours must be confirmed on histopathology, each must be geographically separate and distinct from the other. The lesions must be separated by normal intervening mucosa, and the probability of one being the metastasis of the other must be excluded. [7] Data detailing the occurrence and outcome of dual malignancies in the Indian context are few. Hence we report our experience of 2 years in a Tertiary Care Centre which to the best of our knowledge is the first from Central India with a review of relevant literature.

Case series reports

Our study is a retrospective observational study conducted at the Department of Surgical Oncology in a Tertiary Care Centre between 1 st October 2012 and 31 st September 2014. A total 1255 cases of malignancy were analysed out of which all patients presenting with histologically proven synchronous and metachronous primary as defined by Warren and Gates criteria (1932) were included in our study. Time interval used to differentiated between synchronous and metachronous was taken as 6 months. [8] Various details such as the age of diagnosis of each tumour, sex, family history, whether the tumour was synchronous or metachronous, site of origin, method of diagnosis which included radiological investigation and histopathology confirmation of the tumour, clinical stage at presentation and treatment given were recorded.

Over a period of 2 years, total 12 cases of multiple primary malignancy were noted out of the total 1255 cases (0.95%), five cases were synchronous malignancies, and seven cases were metachronous. Head and neck was the most common site of index malignancy with seven cases (two in synchronous and five in metachronous), followed by breast (three cases) and female gynaecological malignancies (two cases). Most common site for SPM was also head and neck (four cases). Male to female ratio was 1:1.5 in the synchronous primary group and 1:1.3 in the metachronous primary tumour. Median age of presentation of the primary tumour was 52 years and 6 months. The age range for the second primary was 17-72 years. SPM were the highest in the sixth decade of life.

Synchronous second primary malignancy

The median age of diagnosis was 53 years with an age range between 42 and 80 years. Male to female ratio was 1:1.5. Synchronous SPM was highest in the fifth decade. Among synchronous lesions majority of cases were diagnosed incidentally during evaluation of primary (4 out of 5 cases). These 4 cases underwent simultaneous surgery for the index tumour and synchronous SPM. One case was diagnosed incidentally during post-operative evaluation before adjuvant radiation. All our patients in this group are alive and on regular follow-up with the range of survival of 2-23 months with the median of 10 months during our study period [Table 1].
Table 1: Synchronous second primary malignancy (five cases)

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Metachronous second primary malignancy

The age of diagnosis of second tumour ranged between 17 and 72 years. Median age was 52 years for the index tumour and 56 years for the second primary tumour. Metachronous SPM was diagnosed in the sixth decade of life. Male: female ratio was 1.3:1. The time interval between the diagnosis of the index tumour and the secondary tumour was between 7 months and 9 years. A total of 6 out of the 7 cases received complete treatment with adjuvant treatment as per stage of the disease on presentation, one case received incomplete radiation. The most common combination was of a head and neck index tumour developing a second primary in the head and neck region (2 out of 7, 28.57%). Total of four patients opted for treatment of the secondary tumour, one patient with dysgerminoma ovary developed papillary carcinoma thyroid and underwent surgery for the same, one case of carcinoma gingivobuccal sulcus developed carcinoma oropharynx and was managed with chemoradiation alone, the remaining two were managed with upfront surgery and adjuvant chemotherapy ± radiation. A total of 3 out of 7 (42.8%) refused treatment of the second tumour. Five patients were disease free during their period of follow-up. Three cases refused treatment for the SPM, one death was attributable to the progression of secondary tumour remaining two were disease free till their follow-up. One developed local recurrence after completion of treatment for the SPM. Disease-free survival in the metachronous group was 71.4% during our period of study [Table 2].
Table 2: Metachronous second primary malignancy (seven cases)

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  Discussion Top

The presence of multiple primary tumour was reported more than 100 years back by Billroth. [1] The occurrence of multiple primary malignancies is influenced by various genetic events or common environmental risk factors. [9] The pathophysiology behind the occurrence of multiple primary malignancy has been theorised to be common carcinogen-induced multiple cancers in an exposed epithelial surface, termed 'field cancerization' commonly seen in head and neck cancers, as a late side effect of treatment of index tumour and genetic disposition to the tumour. [10] Patients with head and neck squamous cell cancer (HNSCC) are known to have a 36% cumulative lifetime risk of developing the second tumour within 20 years. [11] This is attributed to field carcinogenesis, which is related to exposure to common risk factors such as tobacco and exposure to alcohol. [12] In our study, head and neck cancers were the most common group to develop an SPM 7 out of 12 (58.3%), 2 out of 7 (28.6%) HNSCC gave rise to the synchronous primary tumour which was higher to an Indian study reporting synchronous primary in 1.33%. [13] Out of the 7, only 2 developed secondary head and neck cancer (28.7%) with a history of radiation exposure. The latent period in our study was between 3.5 and 7 years which is less than study reporting a latent period of 15-20 years between exposure to radiation or chemotherapy. [14]

Most of the cases diagnosed synchronously were diagnosed accidentally during staging work up of the primary tumour. Only one patient had complaints attributable to the second primary tumour. Most common mistake committed by practitioners is to label such tumour to be metastatic in nature. Any such unusual presentation should be investigated thoroughly to rule out the rare possibility of a second primary tumour. Multiple tumours that have been pathologically confirmed at the time of presentation should be evaluated and staged as independent tumours. The treatment plan should be decided after staging of both the primary and secondary tumour in view to attain maximum clinical response. Proper counselling and patient's understanding of magnitude of the disease is paramount. Single stage surgery can be offered to treat both the tumour if indicated in majority of cases with low morbidity and mortality. [9],[14],[15] In our study, out of the 5 cases of synchronous malignancy only one case of breast conservation surgery was performed at a later date following Type II modified radical hysterectomy for carcinoma cervix. In 2 out the remaining 4, we have performed safely left modified radical mastectomy with right radical nephrectomy as a single stage procedure resulting in increased surgical time and multiple blood transfusion and prolonged hospital stay and in another case, we performed left modified radical mastectomy along with panhysterectomy with bilateral salpingo-oopherctomy with omentectomy and bilateral retroperitoneal lymph node dissection in the same setting with increase in surgical time and hospital stay.

In our study, the upper aerodigestive tract was the most common site of metachronous tumour in the presence of index HNSCC (5 out of 7). Reported risk of developing SPM in a known case of HNSCC is 2-6% per year of follow-up. [9],[11],[16],[17],[18],[19] Multiple primaries are seen in about 9.7% of head and neck cancer patients including metachronous and synchronous malignancy of which 46.9% presents as synchronous. [20] In our study, 8.5% of total HNSCC had metachronous and synchronous malignancy and 28.6% of all dual primary tumour with index HNSCC were synchronous. This has been attributed to exposure to common carcinogen and the concept of field cancerization and condemned mucosa. [8],[11] SPM tumours related to treatment may arise out of the use of chemotherapeutic agents or due to therapeutic irradiation of the index tumour. [21],[22] Radiation-induced tumour arises in the field of radiation usually after a latent period of 10-15 years. [9],[13] In our study, the latent period was 3.5-7 years, hence confirming the need of strict follow-up protocol with a high degree of clinical suspicion to identify SPM at the earliest. We stress upon the need on a better understanding of SPM and to differentiate it from a metastatic disease. Every effort should be done to look for metastasis from the primary tumour before embarking on surgical management of the both of the index and SPM. Studies show better clinical efficacy in the aggressive treatment of SPM be it in the single setting or as a staged procedure. [9] Apart from sequential SPM that have been documented in literature one should not rule out the occurrence of unusual or new SPM that has not been reported till date. In our study, we report a case of metachronous papillary carcinoma thyroid in a 17 years female patient who was diagnosed with dysgerminoma ovary diagnosed 3 years earlier. Such association has not been found in PubMed search with keywords (papillary carcinoma thyroid, dysgerminoma, dual malignancy, and secondary primary tumour). Such cases are difficult for physicians to educate the patient and the caregivers regarding the occurrence of two primary tumours. We noticed a difference in attitude in patients who were diagnosed with synchronously with SPM and metachronous SPM. A total of 3 out of the 7 metachronous SPM refused further treatment may be due to psychosocial distress, lack of awareness, or financial constraints and were lost to follow-up. In our study, we observed disease free survival varying from 5 to 18 months in three cases of metachronous SPM (42.5%) and 2-14 months in five cases of synchronous SPM (100%). In patients with HNSCC strict follow-up protocol along with counselling against alcohol and tobacco product has to be stressed upon along with the need for a healthy lifestyle.

  Conclusion Top

SPM can occur both in a synchronous or metachronous fashion. Strong clinical acumen and suspicion are required to identify such cases and to differentiate them from metastatic disease, as metastatic disease refers to disease progression and has a poor prognosis. Operable synchronous SPM can be operated in a single setting with minimal morbidity with better survival and is less taxing on the patient and his/her relative both psychologically and financially. A regular follow-up of the patient by the clinician increases the chances of early detection of metachronous SPM and the formulation of the treatment plan at the earliest and hence better overall survival.


Department of Pathology, Department of Radiation Oncology and Department of Medical Oncology, Sri Aurobindo Medical College and PG institute, Indore, Madhya Pradesh, India.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Warren S, Gates O. A survey of the literature and statistical study. Am J Cancer 1932;16:1358-4142.  Back to cited text no. 1
Bittorf B, Kessler H, Merkel S, Brückl W, Wein A, Ballhausen WG, et al. Multiple primary malignancies: An epidemiological and pedigree analysis of 57 patients with at least three tumours. Eur J Surg Oncol 2001;27:302-13.  Back to cited text no. 2
Curtis RE, Freedman DM, Ron E, Ries LA, Hacker DG, Edwards BK, et al. New malignancies among cancer survivors: SEER Cancer Registries, 1973-2000. NIH Publ. No. 05-5302. Bethesda, MD: National Cancer Institute; 2006.  Back to cited text no. 3
Buchler T, Kubankova P, Boublikova L, Donatova Z, Foldyna M, Kanakova J, et al. Detection of second malignancies during long-term follow-up of testicular cancer survivors. Cancer 2011;117:4212-8.  Back to cited text no. 4
Shin DW, Baik YJ, Kim YW, Oh JH, Chung KW, Kim SW, et al. Knowledge, attitudes, and practice on second primary cancer screening among cancer survivors : a0 qualitative study. Patient Educ Couns 2011;85:74-8.  Back to cited text no. 5
Shin DW, Kim YW, Oh JH, Kim SW, Chung KW, Lee WY, et al. Knowledge, attitudes, risk perception, and cancer screening behaviors among cancer survivors. Cancer 2011;117:3850-9.  Back to cited text no. 6
Braakhuis BJ, Tabor MP, Leemans CR, van der Waal I, Snow GB, Brakenhoff RH. Second primary tumors and field cancerization in oral and oropharyngeal cancer : m0 olecular techniques provide new insights and definitions. Head Neck 2002;24:198-206.  Back to cited text no. 7
Morris LG, Sikora AG, Patel SG, Hayes RB, Ganly I. Second primary cancers after an index head and neck cancer : s0 ubsite-specific trends in the era of human papillomavirus-associated oropharyngeal cancer. J Clin Oncol 2011;29:739-46.  Back to cited text no. 8
Hulikal N, Ray S, Thomas J, Fernandes DJ. Second primary malignant neoplasms : a0 clinicopathological analysis from a cancer centre in India. Asian Pac J Cancer Prev 2012;13:6087-91.  Back to cited text no. 9
Van Oijen MG, Slootweg PJ. Oral field cancerization : c0 arcinogen-induced independent events or micrometastatic deposits? Cancer Epidemiol Biomarkers Prev 2000;9:249-56.  Back to cited text no. 10
Morris LG, Sikora AG, Hayes RB, Patel SG, Ganly I. Anatomic sites at elevated risk of second primary cancer after an index head and neck cancer. Cancer Causes Control 2011;22:671-9.  Back to cited text no. 11
Angadi PV, Savitha JK, Rao SS, Sivaranjini Y. Oral field cancerization : c0 urrent evidence and future perspectives. Oral Maxillofac Surg 2012;16:171-80.  Back to cited text no. 12
Krishnatreya M, Rahman T, Kataki AC, Das A, Das AK, Lahkar K. Synchronous primary cancers of the head and neck region and upper aero digestive tract : d0 efining high-risk patients. Indian J Cancer 2013;50:322-6.  Back to cited text no. 13
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Oddou S, Vey N, Viens P, Bardou VJ, Faucher C, Stoppa AM, et al. Second neoplasms following high-dose chemotherapy and autologous stem cell transplantation for malignant lymphomas : a0 report of six cases in a cohort of 171 patients from a single institution. Leuk Lymphoma 1998;31:187-94.  Back to cited text no. 14
Irmie A, Achimas-Cadariu P, Burz C, Puscas E. Multiple primary malignancies-epidemiological analysis at a single tertiary institution. J Gastrointestin Liver Dis 2010;19:69-73.  Back to cited text no. 15
Suzuki S, Nishimaki T, Suzuki T, Kanda T, Nakagawa S, Hatakeyama K. Outcomes of simultaneous resection of synchronous esophageal and extraesophageal carcinomas. J Am Coll Surg 2002;195:23-9.  Back to cited text no. 16
Yamamoto E, Shibuya H, Yoshimura R, Miura M. Site specific dependency of second primary cancer in early stage head and neck squamous cell carcinoma. Cancer 2002;94:2007-14.  Back to cited text no. 17
Sturgis EM, Miller RH. Second primary malignancies in the head and neck cancer patient. Ann Otol Rhinol Laryngol 1995;104:946-54.  Back to cited text no. 18
Tepperman BS, Fitzpatrick PJ. Second respiratory and upper digestive tract cancers after oral cancer. Lancet 1981;2:547-9.  Back to cited text no. 19
León X, Quer M, Diez S, Orús C, López-Pousa A, Burgués J. Second neoplasm in patients with head and neck cancer. Head Neck 1999;21:204-10.  Back to cited text no. 20
Amemiya K, Shibuya H, Yoshimura R, Okada N. The risk of radiation-induced cancer in patients with squamous cell carcinoma of the head and neck and its results of treatment. Br J Radiol 2005;78:1028-33.  Back to cited text no. 21
Gursel B, Meydan D, Özbek N, Ozdemir O, Odabas E. Multiple primary malignant neoplasms from the black sea region of Turkey. J Int Med Res 2011;39:667-74.  Back to cited text no. 22


  [Table 1], [Table 2]

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