Impact of multiple primary cancers on overall survival of patients with hepatocellular carcinoma.

The increasing occurrence of multiple primary cancers (MPC) is a long-term trend, but the prevalence of MPC in patients with hepatocellular carcinoma (HCC) and its impact on overall survival (OS) remains unknown. We retrospectively analyzed 497 patients with HCC treated at two tertiary centers. The cohort was divided into two subgroups - liver transplant (LT, 324 patients) and non-liver transplant (non-LT, 173 patients). We analyzed MPC occurrence, its impact on survival, and identified variables predicting unfavorable outcomes. The MPC were detected in 88 patients (18%). The most common MPC were prostate (17%), skin (15.9%), kidney (12.5%), and lung (10.2%). The median OS of the whole cohort and the LT and non-LT subgroups were 70, 116, and 17 months, respectively (p<0.0001). The median OS in patients with HCC only and HCC with another cancer was 77 (95% CI, 67-96) and 50 months (95% CI, 37-62), respectively (p=0.25). The OS of LT patients was significantly better than that of those in whom LT had been contraindicated owing to concomitant MPC (116 vs. 35 months, p<0.0009). Autoimmune etiology, non-alcoholic steatohepatitis (NASH), HCC as the first diagnosed malignancy, and male sex were identified as factors significantly influencing the patients' outcomes (HR 0.43, 3.2326, 0.70, and 1.43, respectively). The MPC frequency was 18%. The impact of MPC on OS was not significant, except for individuals contraindicated for LT because of MPC. A better prognosis is associated with the autoimmune etiology of cirrhosis, and when HCC is diagnosed as the first malignancy. Male sex and NASH worsened the outcomes.

Case report: A challenging case of severe Cushing's syndrome in the course of metastatic thymic neuroendocrine carcinoma with a synchronous adrenal tumor.

Ectopic ACTH syndrome (EAS) remains one of the most demanding diagnostic and therapeutic challenges for endocrinologists. Thymic neuroendocrine tumors account for 5%-10% of all EAS cases. We report a unique case of a 31-year-old woman with severe EAS caused by primary metastatic combined large-cell neuroendocrine carcinoma and atypical carcinoid of the thymus. The patient presented with severe hypercortisolemia, which was successfully controlled with continuous etomidate infusion. Complex imaging initially failed to detect thymic lesion; however, it revealed a large, inhomogeneous, metabolically active left adrenal mass infiltrating the diaphragm, suspected of primary disease origin. The patient underwent unilateral adrenalectomy, which resulted in hypercortisolemia resolve. The pathology report showed an adenoma with adrenal infarction and necrosis. The thymic tumor was eventually revealed a few weeks later on follow-up imaging studies. Due to local invasion and rapid progression, only partial resection of the thymic tumor was possible, and the patient was started on radio- and chemotherapy.

Fanconi Anemia in a 31-Year-Old Patient with Multiple Malignant Tumor Foci, Including Appendiceal Cancer, and Multiple Coexisting Pathologies.

BACKGROUND Fanconi anemia (FA) is a genetic disorder that impairs the function of the bone marrow and predisposes individuals to aplastic anemia. The condition is caused by mutations in genes responsible for DNA repair. People with FA have an increased risk of developing tumors due to DNA damage. Flat-cell carcinomas of the head, neck, esophagus, and genital organs are often observed in individuals with FA. CASE REPORT A 31-year-old man with Fanconi anemia and a history of bone marrow transplantation was admitted to the General Surgery Department due to elevated levels of the CEA marker. Before the transplantation, chromosomal anomalies, bone marrow hypoplasia, kidney agenesis, and bone defects were noted. After the transplantation, he developed a skin rash. He was also diagnosed with squamous cell carcinoma of the lip and chronic conditions, including cholestatic liver damage, hypertension, and hypothyroidism. During the diagnostic process, computed tomography showed signs of Barrett's esophagus, numerous polyps in the stomach and intestines, and a nodular formation measuring 4.5×5×5.5 cm in the right iliac region. Laparoscopy revealed a neoplasm of the appendix with numerous metastases on the inner abdominal wall and omentum. Histological analysis confirmed mucinous appendiceal cancer. The patient was discharged for palliative treatment at the Oncology Center with a final diagnosis of appendiceal cancer, mucinous type, grade G3. This case underscores the importance of early and comprehensive cancer screening in individuals with FA, particularly those with a history of bone marrow transplantation. CONCLUSIONS This clinical case underscores the critical importance of thorough and timely cancer diagnosis in individuals with this genetic pathology.

Simultaneous bilateral video-assisted thoracic surgery is safe and feasible for multiple primary lung cancers.

BACKGROUND: The treatment for bilateral synchronous multiple primary lung cancers (MPLC) remains challenging. Simultaneous bilateral video-assisted thoracic surgery (VATS) may be an optimal treatment with curative intent, but its safety and feasibility are controversial. METHODS: One hundred and fifty-eight patients who underwent simultaneous bilateral VATS (simultaneous group) and 79 who underwent two-staged bilateral VATS (two-staged group) were included in this study. Their medical records were retrospectively reviewed and analyzed. RESULTS: The majority of patients were female and non-smokers. The most common surgical plan was lobectomy and contralateral wedge resection in both groups. There was no significant difference in the postoperative complication rate between the simultaneous groups and two-staged group (13.3% vs. 11.4%, p = 0.73). Patients who underwent simultaneous bilateral resection had shorter hospital stays, shorter anesthesia time and less chest drainage compared with those who underwent two-staged resection. Advanced TNM stage, complicated surgical plan and aggressive lymph node resection were risk factors for postoperative complications in simultaneous bilateral VATS. Patients in two groups had similar overall survival and disease free survival (p = 0.2). CONCLUSIONS: Simultaneous bilateral VATS for bilateral lung nodule resection is as safe and feasible as two-staged bilateral VATS. Patients who underwent simultaneous bilateral resection had similar or even better outcomes compared to that of the two-staged group. Simultaneous bilateral VATS is potentially an optimal treatment option for patients with erarly cTNM stage and good physical condition.

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.

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.

First report of a successful surgical management of left atrial myxoma coexisting with pulmonary squamous cell carcinoma and thymic cyst.

BACKGROUND: Primary cardiac tumors, while rare, present significant clinical challenges due to their diverse pathology and presentation. Lung cancer frequently metastasizes to the heart; however, cases involving primary cardiac tumors of different origins alongside primary lung cancer are exceedingly rare in the literature. CASE PRESENTATION: We report the case of a 53-year-old female who presented with hemoptysis and was subsequently diagnosed with a left atrial myxoma, pulmonary squamous cell carcinoma, and a thymic cyst. This coexistence of multiple non-homologous tumors in a single patient is exceedingly rare. CONCLUSION: This case underscores the complexity of diagnosing and managing patients with multiple distinct tumors. The simultaneous occurrence of a primary cardiac myxoma, pulmonary squamous cell carcinoma, and thymic cyst is unprecedented, providing valuable insights for future clinical practice.

Accelerated clinical response achieved by combining short-term tumor-directed photodynamic therapy with immunotherapy-based systemic therapies in synchronous colorectal cancer with MSI-H and POLE mutation: a case report.

Genetic sequencing has revolutionized immunotherapy in colorectal cancer (CRC). Recent clinical trials have revealed a positive response to immunotherapy-based systemic therapies in CRC patient subgroups with microsatellite instability (MSI)-High or DNA polymerase epsilon (POLE) mutation. However, the unsatisfactory response rates was the major limitation in real-world practice of the precision immunotherapy in CRC. Adding photodynamic therapy (PDT) to systemic immunotherapy has showed synergetic anti-tumor effect by modulating tumor microenvironment, while the eligible patient's subgroups which would benefit from this combination remained equivocal. Here we reported a synchronous colorectal cancer patient with MSI-High and POLE mutation who had accelerated response in less than 2 cycles (42 days) of immunotherapy-based systemic therapies after tumor-directed PDT and has remained progression-free by far. This case enlightened the synergetic effect of PDT in immunotherapy-treated CRC patients, with the MSI and POLE-mutation status as predictors of survival benefits.

Comparative analysis through propensity score matching in thyroid cancer: unveiling the impact of multiple malignancies.

Background: The incidence of thyroid cancer is on the rise worldwide, with childhood exposure to radiation being the sole acknowledged catalyst for its emergence. Nonetheless, numerous other factors that may pose risks are awaiting thorough examination and validation. This retrospective study aims to explore the malignancies linked to thyroid cancer and contrast the survival rates of those afflicted with a solitary tumor versus those with multiple primary neoplasms (MPN). Methods: This retrospective study examined data from King Hussein Cancer Center (KHCC), Jordan. Among 563 patients diagnosed with thyroid cancer, 30 patients had thyroid malignancy as part of MPN. For a 1:3 propensity score-matched analysis, 90 patients with only a primary thyroid malignancy were also enrolled. Results: Hematologic and breast malignancies were among the most frequent observed cancers alongside thyroid neoplasm. Patients who had MPN were diagnosed at older age, had higher body mass index and presented with higher thyroglobulin antibody levels (p < 0.05 for each). Additionally, MPN patient displayed a stronger family history for cancers (p= 0.002). A median follow-up duration of 135 months unveiled that MPN patients faced a worse 5-year survival compared to their counterparts with a singular neoplasm (87% vs 100% respectively; p < 0.01). However, no distinction emerged in the 5-year event-free survival between these two groups. Conclusion: MPN correlates with a significantly altered survival outcome of thyroid cancer patients. The diagnosis of thyroid carcinoma at an older age, accompanied by elevated initial thyroglobulin antibody levels and a notable familial predisposition, may raise concerns about the potential occurrence of synchronous or metachronous tumors.

Combined Germline and Mosaic SDHA Mutation Is Associated With a Multicancer Syndrome Including Neuroblastoma, Renal Cancer, and Multifocal GI Tumor.

Highlighting here a patient case with neuroblastoma, renal cancer & GIST from germline SDHA.

Multiple neoplasms in patients with uveal melanoma: a systematic review.

PURPOSE: Uveal melanoma is the most prevalent intraocular malignancy in adults, derived from uveal tract melanocytes. This study focuses on the frequency and risk of second primary malignancies in UM patients. METHODS: A PubMed search (1980-2023) identified studies on SPM incidence in UM patients. From 191 references, 14 studies were chosen, focusing on UM, SPMs, and analysing data on demographics and types of neoplasms. RESULTS: Among 31,235 UM patients in 14 studies, 4695 had 4730 SPMs (15.03% prevalence). Prostate (15%), breast (12%), and colorectal (9%) cancers were most common. Digestive system malignancies were highest (19%), with colorectal cancer leading (51%). Breast and prostate cancers were prevalent in respective systems. Lung, bladder, and non-Hodgkin's lymphoma were also notable. The study observed an increasing trend in the frequency of SPMs over time, reflecting broader trends in cancer survivorship and the growing prevalence of multiple malignancies. CONCLUSION: The study highlights a significant presence of SPMs in UM patients, with an increasing trend in frequency over time, emphasizing prostate and breast cancers. This underscores the need for focused surveillance and tailored follow-up for UM survivors, considering their higher risk of additional malignancies. Future research should further investigate SPM aetiology in UM patients.

When synchronous mucinous metaplasia and neoplasia of the female genital tract and peutz-jeghers syndrome meet: a case report and literature reviews.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is characterized by the presence of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation on the lips, oral mucosa, nose, fingers, and toes. Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) refers to the occurrence of multifocal mucinous lesions in at least two sites, including the cervix, uterus, fallopian tubes, and ovaries, in the female genital tract. SMMN-FGT and PJS are rare diseases with a very low incidence, especially when occurring simultaneously. CASE PRESENTATION: We report a case in which a woman with a large mass on the left ovary underwent a gynecological surgery and was diagnosed with cervical gastric-type adenocarcinoma and mucinous lesions in the endometrium, bilateral fallopian tubes, and ovary, i.e., SMMN-FGT, by postoperative paraffin pathology. The patient sought medical attention for abdominal distension and enlargement. A gynecological ultrasound revealed a multilocular cystic mass in the pelvis, while serum tumor markers were within normal limits, with mildly elevated carbohydrate antigen 199 and carbohydrate antigen 125 levels. Cervical thin-prep cytology test result was negative. The patient had a family history of PJS with black spots on her skin and mucous membranes since the age of 8 years. She underwent multiple partial small bowel resections and gastrointestinal polypectomy owing to intestinal obstruction and intussusception. She underwent left adnexectomy, hysterectomy, right salpingectomy, greater omental resection, appendectomy and right ovary biopsy, and received six courses of adjuvant chemotherapy with Lopressor plus Carboplatin. Genetic testing revealed a heterozygous serine threonine kinase 11 germline mutation and there were no signs of recurrence during the 18-month follow-up period after treatment. CONCLUSIONS: This is a rare case in which PJS was complicated by SMMN-FGT. Owing to its extreme rarity, there are no guidelines, but reported cases appear to indicate a poor prognosis. We retrospectively reviewed all cases of collisions between PJS and SMMN-FGT and explored the clinical features, pathological characteristics, diagnosis, treatment methods, and prognosis when the two diseases coexisted. The aim is to deepen the clinicians' understanding of this disease for early detection, diagnosis and treatment.

[Multiple primary tumors in children: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.

A Rare Case of Adenocarcinoma With Micropapillary Structure and Apocrine Differentiation Arising in a Sebaceous Tumor.

ABSTRACT: A 77-year-old Japanese man presented to our hospital with subcutaneous tumors of the right upper arm and axilla. A biopsy revealed a cutaneous adnexal tumor, showing apocrine differentiation, and axillary lymph node metastasis. After chemoradiotherapy to shrink the tumors, both lesions were resected. A resected specimen of the arm tumor showed a variegated histology: (1) a classic sebaceoma with an organoid pattern and sebocytes; (2) a sebaceous tumor with cellular atypia; (3) a papillotubular tumor showing a biphasic pattern of pale eosinophilic cells with apocrine differentiation and basaloid cells; and (4) an invasive adenocarcinoma with a micropapillary structure, reminiscent of an invasive micropapillary carcinoma of the breast. The axillary tumor was regressed. To our knowledge, this is the first reported case of an adnexal tumor of the skin with an invasive micropapillary structure arising in a sebaceous tumor.

Simultaneous primary thyroid MALT lymphoma and papillary thyroid cancer.

The mucosa-associated lymphoid tissue (MALT) lymphoma subtype, specifically extranodal marginal zone B-cell lymphoma, is a rare variant. Within this subtype, primary thyroid MALT lymphoma is an uncommon occurrence. The literature provides limited documentation on thyroid MALT lymphomas, as their prevalence is comparatively lower than in other organ sites. The coexistence of papillary thyroid carcinoma (PTC) and thyroid MALT lymphomas is exceedingly rare. It presents a rare case of primary thyroid MALT lymphoma accompanied by PTC, thyroid lymphoma not being considered before surgery. A 64-year-old female patient, who had been experiencing symptoms related to a substantial thyroid tumor for a duration of three years, she refused to do a needle biopsy before surgery and expressed a preference for surgical resection. Consequently, the patient underwent a total thyroidectomy along with lymphadenectomy of the central compartment. A histological examination subsequently confirmed the presence of papillary thyroid carcinoma (PTC) and mucosa-associated lymphoid tissue (MALT) lymphoma. Due to the favorable response of the MALT lymphoma to local treatment and the absence of metastasis in other organs, no further treatment was administered for the MALT lymphoma following the surgery. Currently, the patient exhibits no signs of tumor recurrence based on ultrasound and laboratory evaluations. We also provide an overview of the clinical findings on PTC and MALT lymphoma patients already reported and discuss the possible treatment strategy.

[Cowden syndrome in a male patient with metachronous triple cancers and various clinical features:a case report].

A 66-year-old male patient with a thyroid and nasopharyngeal cancer history visited our hospital because of a positive fecal occult blood test. Total colonoscopy detected sessile or subpedunculated polyps in the ascending colon, sigmoid colon, and rectum. These polyps were endoscopically resected, and the rectal polyp was pathologically diagnosed as adenocarcinoma in adenoma and the others as adenomas. Additionally, multiple sessile lesions were revealed in the sigmoid colon and rectum. A complete gastrointestinal tract examination revealed multiple foci of glycogenic acanthosis in the esophagus, multiple sessile lesions in the stomach, multiple sessile lesions, clubbings (rod-shaped lesions), and venous malformations in the small bowel. Mucocutaneous examination indicated hemangiomas on the body trunk, patchy pigmentation on the glans penis, and keratotic papules in the inguinal region. The National Comprehensive Cancer Network diagnostic criteria for Cowden syndrome were used in this case. The patient met four major and two minor criteria;thus, Cowden syndrome was diagnosed. Moreover, the patient was had phosphatase and tensin homolog deleted on chromosome 10 gene mutation. This is the first reported case of metachronal triple cancers in a male patient with Cowden syndrome, and our results indicate the importance of cancer surveillance.