Genomic and immune heterogeneity of multiple synchronous lung adenocarcinoma at different developmental stages.

Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.

A randomized phase III trial of stereotactic ablative radiotherapy for patients with up to 10 oligometastases and a synchronous primary tumor (SABR-SYNC): study protocol.

BACKGROUND: Emerging randomized data, mostly from phase II trials, have suggested that patients with oligometastatic cancers may benefit from ablative treatments such as stereotactic ablative radiotherapy (SABR). However, phase III data testing this paradigm are lacking, and many studies have examined SABR in the setting of metachronous oligometastatic disease. The goal of the SABR-SYNC trial is to assess the effect of SABR in patients with oligometastatic cancers and a synchronous primary tumor. METHODS: One hundred and eighty patients will be randomized in a 1:2 ratio between standard of care (SOC) palliative-intent treatments vs. SOC + ablative therapy (SABR preferred) to all sites of known disease. Randomization will be stratified based on histology and number of metastases at enrollment. SABR may be delivered in 1-, 3- and 5-fraction regimens, with recommended doses of 20 Gy, 30 Gy, and 35 Gy, respectively. Non-SABR local modalities (e.g. surgery, thermal ablation, conventional radiation) may be used for treatment of the primary or metastases at the discretion of the treating physicians, if those modalities are clinically preferred. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, time to initiation of next systemic therapy, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor DNA and immunological predictors of outcomes. DISCUSSION: SABR-SYNC will provide phase III data to assess the impact of SABR on overall survival in a population of patients with synchronous oligometastases. The translational component will attempt to identify novel prognostic and predictive biomarkers to aid in clinical decision making. TRIAL REGISTRATION: Clinicaltrials.gov NCT05717166 (registration date: Feb. 8, 2023).

Simultaneous occurrence of papillary thyroid carcinoma, medullary thyroid carcinoma, and lymphoma: A case report.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, the coexistence of PTC and medullary thyroid carcinoma (MTC) is uncommon. While the simultaneous occurrence of both cancers with small lymphocytic lymphoma (SLL) in lymph nodes with PTC metastasis is very rare. This study presents a unique case of concurrent PTC, MTC, and SLL, highlighting the exceptional rarity of these coexisting tumors. METHODS: A 75-year-old female with a thyroid tumor underwent total thyroidectomy, bilateral central neck lymph node dissection, and right radical neck lymph node dissection. Histopathological examination revealed a low-grade medullary thyroid carcinoma (MTC) in the left lobe and classical papillary thyroid carcinoma (PTC) in the right lobe, with PTC metastasis in the cervical lymph nodes and concurrent SLL in the affected lymph nodes. RESULTS: Coexistence of PTC, MTC and SLL in the same patient is rare, there are currently no standardized treatment guidelines due to the limited literature. However, it is essential to consider not only the treatment for each type of tumor but also the potential risks or conflicts associated with the treatments. In the case reported in this paper, the papillary carcinoma invaded the capsule of the right lobe of the thyroid and metastasized to the cervical lymph nodes, warranting radioactive iodine therapy. However, considering the potential negative impact of radioactive iodine on the pre-existing lymphoma, the radioactive iodine therapy was postponed. Meanwhile, constant monitoring of calcitonin and thyroid globulin should be performed to monitor tumor recurrence as was performed in the present case. CONCLUSION: Since MTC, PTC, and SLL may coexist, patients with PTC deserve careful surveillance for the other disease entities. This case underscores the need for heightened awareness among clinicians, radiologists, and pathologists regarding the possibility of concurrent thyroid tumors and abnormal lymph nodes, guiding comprehensive pre-operative evaluations and postoperative monitoring strategies. This study aims to provide a warning for routine pathological diagnosis and contribute data for related research.

A rare association of pheochromocytoma, paraganglioma, and pituitary adenoma (3PA): A case report and literature review.

RATIONALE: 3P association (3PA) is a rare condition with co-occurrence of pituitary adenoma and pheochromocytoma/paraganglioma. There have been less than a hundred documented cases of 3PA, which can be sporadic or related to genetic mutations. The present case report describes the first Iranian patient with 3PA and a 90th case of 3PA in the available literature. PATIENT CONCERNS AND INTERVENTIONS: A 36-year-old Caucasian male was admitted with headache and sudden increase in blood pressure. An abdominal CT scan revealed a retroperitoneal mass posterior to the inferior vena cava, later removed and diagnosed as a pheochromocytoma. Four years later, he noticed occasional mild headaches and a painless mass on the right side of his neck. The ultrasonography evaluations suggested a carotid body tumor, which was surgically removed. About a month after his second surgery, the severity of the patient's headaches worsened, and he developed right homonymous hemianopia. A brain MRI showed a mass in favor of macroadenoma, craniopharyngioma, or meningioma, and elevated prolactin level led to the diagnosis of macroprolactinoma. DIAGNOSES: Based on the provided history, this patient was diagnosed with 3PA, and a genetic study identified a positive succinate-dehydrogenase-complex subunit b mutation, possibly linked to his family history of carotid body tumor. OUTCOMES: He has remained symptom-free during his visits every 3 months. LESSONS: The number of cases diagnosed with 3PA worldwide is increasing. Using clinical and genetic assessments, we can timely diagnose and adequately monitor individuals with or at risk of 3PA.

Acute myeloid leukemia with gastric carcinoma: A case report of a double malignancy.

RATIONALE: Multiple primary cancers (MPC) are malignant tumors that manifest as multiple primary tumors diagnosed in the same patient, either simultaneously or sequentially. Billroth first proposed the concept in 1889. Here, we report a rare case of untreated acute myeloid leukemia (AML) and adenocarcinoma of the cardia. PATIENT CONCERNS: A 58-year-old male with muscle and joint pain for >1 month was admitted to the hospital with severe chest pain for 3 hours on July 14, 2023. The patient had chest tightness, shortness of breath, and dyspnea. The skin, mucosa, and lips of the patient were slightly pale and the sternum had mild tenderness. Other systemic examinations did not reveal any obvious abnormalities. The results of routine blood tests on admission were as follows: white blood cells, 7.46 × 109/L; red blood cells, 2.32 × 1012/L; hemoglobin, 90 g/L; and platelets, 62 × 109/L. DIAGNOSIS: The patient was diagnosed with acute myeloid leukemia (FLT3, DNMT3A, U2AF1, and SMC3 mutations; KMT2A amplification; high-risk) and adenocarcinoma of the cardia. INTERVENTIONS: The patient was treated with azacitidine + Veneckla chemotherapy, and through precise regulation, the patient survived the period of bone marrow suppression. He was unable to achieve complete relief and finally underwent allogeneic hematopoietic stem cell transplantation in February 2024. OUTCOMES: Bone marrow cytology and minimal residual disease analysis indicated complete relief on April 22, 2024, with the bone marrow exhibiting complete chimerism (99.63%). The patient and his family members decided to seize the opportunity to perform radical surgical treatment for gastric cancer on May 16, 2024. LESSONS: The development of medicine, especially in oncology, has led to an increased possibility of developing multiple cancers. Clinically, some doctors may not be aware of the existence of multiple primary cancers, especially simultaneous carcinomas, which can be easily missed or misdiagnosed.

Impact of tumor multiplicity on the prognosis of patients with primary renal cell carcinoma: a SEER database analysis.

To compare clinical characteristics and survival outcomes of patients with multiple renal cell carcinoma versus single renal cell carcinoma. Develop a prognostic model for predicting prognosis in patients with multiple tumors and analyze prognostic factors. Patients with primary multiple renal cell carcinoma were selected from the Surveillance, Epidemiology, and End Results database (2004-2015). They were divided into single-tumor and multiple-tumor groups. Survival analysis was conducted using the Kaplan-Meier method and log-rank test. A Cox regression model was used to identify potential prognostic factors. A total of 19,489 renal cell carcinoma cases were included, with 947 in the multiple-tumor group and 18,542 in the single-tumor group. The multiple-tumor group had lower cancer-specific survival (P = 0.03, HR = 1.431). Cox regression identified risk factors for the multiple-tumor group including number of tumors, gender, combined summary stage, T stage, N stage, tumor size, and type of surgery. The predicted probabilities showed acceptable agreement with the actual observations at 3-, 5-, and 8-years area under the curve values in both the training and validation cohorts (0.831 vs. 0.605; 0.775 vs. 0.672; and 0.797 vs. 0.699, respectively). Compared with single renal cell carcinoma, multiple renal cell carcinoma is associated with decreased cancer-specific survival. Additionally, we identified several prognostic factors including the number of tumors, T stage, tumor size, and type of surgery. These findings offer valuable insights for selecting appropriate treatment strategies for patients diagnosed with multiple renal cell carcinomas.

[Synchronous primary multiple cancer: distal cholangiocarcinoma of the intrapancreatic common bile duct and intraductal papillary mucinous tumor associated with ductal adenocarcinoma of the pancreatic tail]. / Sinkhronnyi pervichno-mnozhestvennyi rak: distal'naya kholangiokartsinoma intrapankreaticheskoi chasti obshchego zhelchnogo protoka i vnutriprotokovaya papillyarnaya mutsinoznaya opukhol' v assotsiatsii s protokovoi adenokartsinomoi khvosta podzheludochnoi zhelezy.

We present a combination of distal cholangiocarcinoma of the intrapancreatic common bile duct and intraductal papillary mucinous tumor associated with ductal adenocarcinoma of the pancreatic tail. This clinical case is unique. When analyzing the literature, we found no any case of similar primary multiple malignant tumor. Importantly, final diagnosis of simultaneous malignant pancreatobiliary neoplasia is possible only via intraoperative biopsy after adequate morphological dissection and research of resected organ complex including molecular genetic analysis due to identical histological and immunohistochemical picture of ductal neoplasia.

Usefulness of Deloyers procedure with minimally invasive coloproctectomy in an elderly patient with synchronous colorectal cancer: A case report.

Subtotal colectomy is often performed on patients with synchronous colorectal cancer. However, compared with colorectal anastomosis, ileorectal anastomosis with subtotal colectomy is more likely to result in bowel dysfunction. The Deloyers procedure is useful in preserving bowel function in a patient with synchronous colorectal cancer. An 87-year-old man presented with bloody stool. Colonoscopy showed masses in the cecum, transverse colon, rectosigmoid, and rectum above the peritoneal reflection. Computed tomography scan revealed no evidence of regional lymph node swelling and distant metastasis. Therefore, robot-assisted low anterior resection, laparoscopic extended left hemicolectomy, laparoscopic cecal resection, and diverting ileostomy were performed. The patient was discharged from the hospital without complications. There was no recurrence, and the patient did not have complaints such as urgency, fecal incontinence, and excretory dysfunction. Hence, minimally invasive coloproctectomy using the Deloyers procedure can be safe and useful in preserving postoperative bowel function in elderly patients.

[Simultaneous occurrence of facial neurinoma in internal auditory canal and middle ear paraganglioma in patient. Unusual combination and difficult surgical task]. / Odnovremennoe vozniknovenie nevrinomy litsevogo nerva vo vnutrennem slukhovom prokhode i paragangliomy srednego ukha u patsientki: neobychnoe sochetanie i neprostaya khirurgicheskaya zadacha.

CLINICAL CASE: The 59-year-old patient complained of hearing loss on the left, ear murmur for a long time, periodic pain and discomfort in the left ear, dizziness for 6 months. She was found to have concurrent vestibular schwannoma in the internal auditory canal and temporal bone paraganglioma. Both tumors were removed in one operation. The schwannoma was removed by translabirinth access due to preoperative deafness, while the glomus tumor was removed during this access. Postoperative biopsy showed the presence of two unrelated diseases: paraganglioma (ICD-0 code 8690/3) and schwannoma (ICD-0 code 9560/0).

[A Case Report of Adenomyoepithelioma Coexisting with Apocrine Carcinoma in Contralateral Breasts].

Adenomyoepithelioma(AME)of the breast is a rare condition, and comorbidity with carcinoma is even more unusual. Herein, we report a case of both AME and apocrine carcinoma in different breasts of a single patient. A 48-year-old woman presented to our clinic with a right breast tumor. Fine needle aspiration cytology(FNAC)was indeterminate and suspicious for both papilloma and non-invasive ductal carcinoma, but excisional biopsy indicated an AME. Immuno-histochemical staining showed EMA(+), AE1/3(+), and CK7(+)mammary duct cells and αSMA(+), CK5/6(+), and p63(+) myoepithelial cells. Six months later, the patient noticed a left breast tumor, and although FNAC indicated no malignancy, after 6 additional months, the tumor size had increased and a mammography revealed tumor microcalcification, suggesting malignancy. Vacuum-assisted biopsy revealed an apocrine carcinoma. The patient underwent partial mastectomy and sentinel node biopsy, followed by radiotherapy and chemotherapy. The post-surgical pathology was pT1pN0M0, Stage Ⅰ, triple- negative, and the patient was disease-free for 12 years postoperatively. To our knowledge, this is only the second case of AME and breast cancer in different breasts reported in Japan.

Repeat Next-Generation Sequencing (15-Gene Panel) in Unifocal, Synchronous, and Metachronous Non-Small-Cell Lung Cancer-A Single-Center Experience.

In advanced non-squamous non-small-cell lung cancer (NSCLC), routine testing with next-generation sequencing (NGS) is recommended to identify actionable genomic alterations (AGAs). The therapeutic implications of repeated NGS testing on synchronous and metachronous tumors are unclear. Between February 2017 and October 2020, NSCLC samples from a single institution were reflex-tested using a targeted 15-gene NGS panel (TruSight Tumor 15, Illumina). Thirty-eight patients were identified with multiple NGS results from 82 samples: 11% were from single unifocal, 51% were from synchronous, and 38% were from metachronous tumors. Changes in EGFR, KRAS, PI3KCA, and TP53 variants were found in 22 patients' samples (58%). No changes were seen with longitudinal testing of multiple samples from single unifocal tumors, while changes were observed in 60% of synchronous and 71% of metachronous tumors. Of these, 26% of patients had AGA differences between samples. Acknowledging the limited sample size, a significant difference in overall survival was observed between synchronous separate primaries and metastasis. Repeat NGS testing of synchronous and metachronous NSCLC tumors may identify differing variants in >50% of patients. These changes may reflect separate primary lung carcinomas, tumor heterogeneity among intrapulmonary metastases, and clonal evolution. NGS testing of multiple tumors may enhance the identification of therapeutic targets for treatment decisions.

Synchronous cemento-ossifying fibromas: a systematic review.

BACKGROUND: This systematic review aimed to incorporate published data regarding synchronous cemento-ossifying fibromas (COF), with an analysis of their demographic and clinicopathological characteristics. MATERIAL AND METHODS: Case reports and case series of synchronous COF were searched in PubMed, Web of Science, Scopus, EMBASE, and LILACS according to the PRISMA (2020) statement. Also, a manual search was carried out and the grey literature was assessed. A descriptive statistical analysis was performed. RESULTS: Nineteen studies comprising 20 cases of synchronous COF were included. The mean age at diagnosis was 35 years (±13.8), with a predominance of female patients (n=12/60%). In 13 cases (65%) the mandible and the maxilla were affected simultaneously. In two cases (10%) first-degree relatives (parents or siblings) had been previously diagnosed with COF. The diagnostic hypotheses were reported in 8 cases (40%), with florid cemento-osseous dysplasia, ameloblastic fibroodontoma, calcifying cystic odontogenic tumor, osteoma and cementoblastoma being cited in the differential diagnosis. Among the cases with details about management (n=17), eleven were treated by surgical enucleation and/or excision (64.7%). Follow-up was provided for 10 cases (50%), with a mean period of 44.7±62.19 months. Recurrence occurred in three of informed cases. CONCLUSIONS: Synchronous manifestation of COF is rare. Female patients around the 3rd decade of life are more commonly affected. Bilateral involvement of the mandible and maxilla is the most common clinical presentation.

Germline BRCA1-Mutated Synchronous and Metachronous Pancreatic Acinar Cell Carcinoma With Long-Term Survival.

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic neoplasm. Recently, molecular analysis revealed that PACC shows a high frequency of the BRCA1/2 mutation and is likely to be considered a cancer associated with hereditary breast and ovarian cancer (HBOC). Hereditary cancers, including HBOC, are characterized by multifocal and/or metachronous tumors. However, no case reports exist of germline BRCA1-mutated synchronous and metachronous PACC. CASE: A 58-year-old man was diagnosed with synchronous and metachronous PACC at the age of 56 and underwent two surgeries. Ten months after the second surgery, the patient developed multiple liver metastases. Gemcitabine plus nab-paclitaxel therapy was administered as first-line chemotherapy. After seven cycles, computed tomography examination revealed progressive disease (PD). Therefore, modified FOLFIRINOX (mFFX) was administered as second- line chemotherapy. After 19 cycles of mFFX, comprehensive cancer genomic profiling (CGP) identified a BRCA1 pathogenic variant that was confirmed to be germline origin. Accordingly, we treated the patient with olaparib; however, he was diagnosed with PD after 4 months. He subsequently died 5 years and 9 months after the initial surgery, and 3 years and 10 months after chemotherapy. Based on the genetic data of the patients, his family members received genetic counseling followed by cascade testing. Consequently, the same gBRCA1 pathogenic variant was detected in the son and his surveillance for HBOC-related cancers was initiated. CONCLUSION: We diagnosed a 58-year-old man with a synchronous and metachronous PACC with germline BRCA1 pathogenic variant. Considering that PACC is likely to have BRCA1/2 mutations responsible for HBOC, we need to be aware of the possible presence of multifocal and/or metachronous tumors in patients with PACC. Additionally, patients with PACC should undergo genetic examinations, which would be beneficial in determining treatment strategies and health care for blood relatives.

Stereotactic body radiation therapy for multiple lung cancers in a patient with six primary cancers: a case report.

BACKGROUND: Surgery is the standard care for patients with early-stage lung cancer, and stereotactic body radiation therapy is an option for those who are medically inoperable or refuse surgery. Medical developments in diagnostic and therapeutic strategies would prolong prognosis of patients with cancer. The number of patients with multiple cancers has also increased. Duplex primary malignant neoplasms are the most common, and triple or more primary malignant neoplasms were extremely rare. This is the first case of sextuple primary malignant neoplasms with lung cancer. CASE PRESENTATION: We report a case of two courses of stereotactic body radiation therapy for an 88-year-old Japanese male patient with six primary cancers in five organs. Cancers were detected in the thyroid, prostate, esophagus, bladder, and lungs. He also had a history of angina pectoris and had undergone percutaneous coronary intervention. Although he was capable of undergoing surgery for lung cancers, he refused it because he had experienced many invasive treatments, such as surgeries and percutaneous coronary intervention. In January 2020, the first stereotactic body radiation therapy was performed for the adenocarcinoma in the right lung. In March 2022, the second stereotactic body radiation therapy was performed for the nodule of the left lung. Although he complained of mild dyspnea after the first stereotactic body radiation therapy, we did not use steroids because his peripheral oxygen saturation was within the normal range. He had pleural effusion, cardiac dilatation, and pericardial effusion 2 months after the second stereotactic body radiation therapy, which improved with the use of compression stockings. CONCLUSION: A total of 43 and 17 months have passed since the first and second stereotactic body radiation therapy, respectively, there is no local recurrence and the patient can walk independently. We safely performed stereotactic body radiation therapy twice for our older patient with metachronous early-stage lung cancers. If another new tumor is detected, stereotactic body radiation therapy would be a good treatment option for the functional preservation of organs.

Synchronous laryngeal cancer.

Multiple primary cancers are usually defined as primary malignant tumors of different histological origins in one person. Synchronous cancers are defined as two or more primary cancers diagnosed in the same patient at the same time or within six months after identifying the first tumor, and those cancers that develop at more than a six-month interval are termed as metachronous multiple primary cancers. Our study comprised of a patient with synchronous laryngeal cancer with double localizations. The case was solved through surgical excision of the tumors. Histopathological and immunohistochemistry examinations revealed synchronous laryngeal cancer. Laryngeal cancer should usually be managed through surgical resection, followed by oncological treatment.

Composite eosinophilic solid and cystic renal cell carcinoma and clear cell renal cell carcinoma: a rare case report and literature review.

BACKGROUND: Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a novel subtype of renal cell carcinoma characterized by its relatively low incidence and indolent behavior. We report a rare case of ESC-RCC concurrent with clear cell renal cell carcinoma (ccRCC) in a single kidney. CASE PRESENTATION: A 48-year-old male, was found to have a mixed echogenic mass in the left kidney during a physical examination. He has no history of hematuria and flank pain. An abdominal CT scan revealed a 3.0 * 1.9 * 2.5 cm3 mass with unclearly bordered at the lower pole of the left kidney. Abdominal MRI showed two nodules of different sizes in the left kidney, suggesting the possibility of a tumor. The patient underwent a subtotal nephrectomy, and the postoperative pathological results indicated ESC-RCC combined with ccRCC. The patient recovered well without tumor recurrence during the 12-month follow-up. CONCLUSION: We reported a case of renal composite tumors, comprising the rare ESC-RCC and the more common ccRCC. Imaging combined with postoperative pathological examination is crucial for the definitive diagnosis of these rare tumors.

Clinicopathological analysis of patients with dual malignancies: A retrospective study.

BACKGROUND: This study aims to report the increasing incidence of second primary malignancies to better understand the association of multiple primary cancers and the duration of their occurrence. Keeping in view the current trends in dual malignancies and to further emphasize the importance of screening and follow-up diagnosis, we reviewed the records of patients who were diagnosed with dual malignancies. MATERIAL AND METHODS: This is a retrospective observational study. We collected data from the hospital database, of patients presenting with either histologically proven synchronous or metachronous double primaries between January 1, 2017, and December 31, 2021. The time interval to differentiate between synchronous and metachronous has been taken as 6 months. RESULTS: During the period of five years, twenty-three patients presented with dual malignancy. Out of 23 cases, seven were synchronous (30.43%), and 16 were metachronous (69.56%). In the synchronous malignancy group, the most common site of first and second primary malignancy was breast [5 cases (71.4%) and 3 cases (42.8%), respectively]. In the metachronous malignancy group, the most common site of the first primary was breast (7 cases; 43.75%), followed by the head and neck (4 cases; 25%), and the most common site of the second primary was also the breast (6 cases; 37.5%), followed by the lung (5 cases; 31.25%). CONCLUSION: Second primary malignancies are not rare and can occur at any age. Regular follow-up and screening procedures by the treating oncologist can play a major role in early detection followed by appropriate treatment of second primary tumors.

A prospective observational study to assess the epidemiological profile of multiple primary cancers in Eastern India.

BACKGROUND: Multiple primary cancers once thought to be rare have become increasingly common as the lifespan of cancer survivors has increased with availability of better and more effective cancer treatment. However, their exact incidence is not known and data on their epidemiological characteristics are not available. AIM: The aim of this study is to study the epidemiologic characteristics of multiple primary cancers in the eastern region of India. MATERIALS AND METHOD: The study was conducted in the Department of Surgical Oncology, Medical College, Kolkata, from 2017 to 2020 over a period of 3 years. All patients with a diagnosis of second primary as per International Agency for Research on Cancer (IARC) definition or those developing a second primary within the study period were included for analysis. Data were recorded in form of preformed questionnaires. All the cases were followed up for at least 12 months. RESULT: Fifty cases of multiple primary tumors were identified, out of which 21 were synchronous while rest 29 were metachronous type. The male-female ratio was 1:1.2. The median age at presentation for index malignancy was 50 years. The most common malignancy in the synchronous group was a combination of variety of GI cancers (six cases). In the metachronous category, a combination of reproductive cancers (breast, ovary, cervix, and endometrium) along with Gastrointestinal cancer (GI) cancers (colon, rectum) was most frequently found (eight cases). Definite risk factors for multiple primary tumors were identifiable in 10 cases: arsenic exposure in 5 cases, hereditary in 4 cases, and immunosuppression in 1, while in 8 cases, risk factors were only speculative (radiation 5 cases, chemotherapy 3). At the time of the last follow-up, 36 subjects were alive and 3 dead while the status of 11 subjects was unknown. CONCLUSION: This is the first comprehensive study on multiple primary cancers and the largest so far in India. Our study overcomes the shortcoming of previous case series from our subcontinent. The merits of our study include the use of the most accepted IARC definition, updated staging guidelines with long follow-up, and reliable survival data. Additionally, we could identify risk factors in 50% of our subjects. And our study shows various new combinations of cancers not reported before. Clustering of cases in the young adolescent group (25-49) years is also a new finding. We also highlight the existing ambiguity in the way this entity is defined. Demerits include the loss of follow-up data in a significant number of patients.