Multiple Primary Malignancies Research Articles

Synchronous primary gastric diffuse large B-cell lymphoma and multiple lung primary adenocarcinoma with pulmonary cryptococosis: a case report and literature review

BackgroundThe coexistence of non-Hodgkin’s lymphoma of the stomach and multiple primary lung adenocarcinomas with pulmonary cryptococcosis has rarely been reported.Case presentationWe herein present a 75-year-old man who was admitted to our hospital due to hematemesis. Gastroscopy and imaging revealed extensive stomach wall thickening and multiple lung lesions, including nodules and cavernous lesion. The patient was diagnosed with primary diffuse large B-cell lymphoma via gastroscopy and bilateral lung primary adenocarcinoma with cryptococcal infection via percutaneous CT-guided puncture biopsy. He subsequently underwent six cycles of R-CHOP regimen for gastric lymphoma, along with CT-guided radiofrequency ablation for the upper lobe of the right lung primary adenocarcinoma and radioactive particle implantation was performed on the lower lobe of the left lung primary adenocarcinoma, supplemented with antifungal therapy. After a definite diagnosis and systemic treatment, the patient was followed up for twenty-seven months with no tumor recurrence, progression or metastasis.ConclusionTo the best of our knowledge, the complex combination of multiple primary malignancies and pulmonary cryptococcal infection is extremely rare. The diagnosis is been confusing and challenging. CT-guided needle biopsy can help achieve pathological diagnosis, elucidate the type and stage of the tumor, and even change the clinical treatment strategy, which is necessary and beneficial.

Multiple primary malignancies: sequential development of Ewing sarcoma and carcinoid tumor in a single patient

Introduction and importance: Multiple primary malignancies (MPMs) involve two or more distinct primary cancers in one individual, either simultaneously or at different times. The incidence of MPMs is rising due to advancements in cancer detection, improved survival rates, and long-term treatment effects. This case report, likely the first of its kind, highlights a rare instance of a 30-year-old female developing a carcinoid tumor 5 years after Ewing sarcoma, emphasizing the need for vigilant monitoring of cancer survivors. Case presentation: A 30-year-old female with a history of Ewing Sarcoma diagnosed 5 years prior, initially presenting with a vascular, hard mass on her right shoulder, underwent neoadjuvant chemotherapy and surgical excision. She recently presented with high-grade fever, cough, weight loss, and severe chest pain. Imaging and biopsy confirmed a high-grade carcinoid tumor. Histopathology showed positive markers for Synaptophysin, CD56, and Chromogranin, with a Ki-67 index of 30–40%. The patient passed away after one cycle of chemotherapy. Clinical discussion: Diagnosing and managing MPMs is challenging due to the complexity of distinguishing primary tumors from metastases. This case fits the Warren and Gates’ criteria for MPMs. This case confirmed Ewing sarcoma and atypical carcinoid tumor as distinct primary malignancies. Delayed diagnosis worsens outcomes, especially for aggressive atypical carcinoids. This case underscores the importance of thorough diagnostics, long-term follow-up, and improved healthcare infrastructure. Conclusion: This case report emphasizes the importance of a multidisciplinary approach, regular follow-ups, and timely detection for effective management of MPMs.

Synchronous Head and Neck Squamous Cell Carcinoma and Hematologic Malignancies

Synchronous occurrence of solid tumors and hematological malignancy is a rare condition. There is no standard management or therapy for this complicated situation. The authors systematically reviewed articles searched using online databases. The patients are predominantly male, and the average age is similar to each malignancy. According to these studies, most patients are treated in order of aggressiveness. However, when a patient has multiple primary malignancies, all of which are aggressive, the treatment decision is challenging. Due to the limited number of cases, it is hard to have a firm conclusion about an optimal treatment policy. It appears that poor outcomes are mostly related to less adequate therapy. Because the condition is complicated in such cases and there is no standardized treatment, patients should be treated on an individual basis with treatments customized to a given patient’s particular circumstances. In addition, multidisciplinary communication and cooperation are crucial in the management of these patients. More in-depth research is still needed to reach a more conclusive treatment strategy and predictable outcomes.

Synchronous multiple primary malignancies or transdifferentiation?-A diagnostic challenge in a case of Xeroderma pigmentosum.

A diagnosis of synchronous tumors is always questionable when they show similar histology. We present a case of synchronous tumors, i.e. melanoma (MM) arising from the scalp and angiosarcoma (AS) from the cheek in a patient of Xeroderma pigmentosum (XP). The presence of melanin in AS of the cheek led to a differential diagnosis and a possibility of transdifferentiation of malignant melanoma in the first instance. Immunohistochemistry (IHC) was negative for melanoma markers (Melan A, SOX-10 & S 100) and positive for vascular markers (ERG, CD31 & CD34) ruling out transdifferentiation and concluding the cheek swelling as angiosarcoma. The presence of non-cutaneous malignancies is rare in XP and the presence of MM in a nearby site and the melanin pigment in the cutaneous malignancy mislead the diagnosis. The morphology of the tumor was the key which led to the further workup of the case.

1372P Advanced non-small cell lung carcinoma in the era of immunotherapy: Survival and the risk of multiple primary malignancies

1372P Advanced non-small cell lung carcinoma in the era of immunotherapy: Survival and the risk of multiple primary malignancies

CAUSES OF MORBIDITY AND MORTALITY IN STELLER SEA LIONS (EUMETOPIAS JUBATUS) UNDER PROFESSIONAL CARE IN NORTH AMERICAN AQUARIUMS FROM 1979 TO 2021.

To date, published comprehensive pathology investigations documented in Steller sea lions (SSL; Eumetopias jubatus) are from free-ranging populations, whereas health data from those under professional care in aquariums are currently lacking. A retrospective review of gross and histopathologic reports of SSL under human care in North American aquariums from 1979 to 2021 (n = 20) was performed. Associations between age, sex, or birth origin (born in aquariums versus the wild) with cause of death (COD) and comorbidities were explored. Age was significantly associated with development of endocrine organ pathology (P = 0.011). A relationship between age and both cardiovascular and ocular disease was suggested by the data, but did not reach significance (P = 0.058). Ocular disease was significantly associated with being born in aquariums (P = 0.022). The most common COD was neoplasia (n = 10), which was significantly associated with aged animals (P = 0.038). Less frequent COD included sepsis (confirmed, n = 2; suspected, n = 3), cardiomyopathy (n = 1), clostridial enteritis (n = 1), Sarcocystis spp. (n = 1), complication secondary to sedation (n = 1), and unknown (n = 1). This is the first report documenting the high prevalence of neoplasia in SSL, with tumors found incidentally in three individuals, frequent metastasis (10/13, 77%), and many cases of multiple primary malignancies (6/13, 46%). These data expand upon the current understanding of disease in SSL, highlight this species' predisposition to neoplasia with increasing longevity, and underscore the need for heightened screening in aged animals, which may ultimately serve to elevate the care of SSL under professional care in aquariums.

Trifecta of Tumors: Simultaneous Detection of Three Primary Malignancies by Different Radiotracers of Nuclear Medicine

AbstractMalignancies are increasing worldwide with changing lifestyle, pollution, increasing life expectancy, and diagnostic advancements. However, multiple primary malignancies (MPMs) detected simultaneously are very rare. Here, we present a rare case of three primary malignancies (sigmoid colon, prostate, and thyroid) detected simultaneously in a 77-year-old male patient, who initially presented with bleeding per rectum and was then found to have a large pedunculated mass in the sigmoid colon on colonoscopy, which further turned out to be adenocarcinoma. On further imaging and investigations, two new separate malignancies (prostate and thyroid) were found by two different positron emission tomography radiotracers: prostate-specific membrane antigen (PSMA) and fluorodeoxyglucose (FDG). Hence, nuclear medicine modalities can play an important role in detecting MPMs using the vast array of radiotracers available now and perhaps reduce the need for multiple biopsies.

Clinicopathological Characteristics of Multiple Primary Malignancies Involving Female Genital Tract at a Tertiary Cancer Institute of Northeast India

ABSTRACT Background: The term “Multiple Primary Malignant Neoplasms (MPMNs)” refers to two or more unrelated primary malignant neoplasms that originate from single or different organs and occur in one patient. MPMNs have been divided into synchronous and metachronous based on time duration after first malignancy. Materials and Methods: This was a hospital-based retrospective study conducted at a tertiary cancer institute in Northeast India. Clinicopathological factors of patients with multiple primary malignancies with at least one female genital tract malignancy attending the gynecological oncology outpatient department were observed. Those with ambiguous status of primary malignancy and incomplete treatment of first primary malignancy were excluded from the study. Results: A total of 57 patients with MPMN, including one case of triple primary malignancy, were included in the study. 59.18% of cases had metachronous, and 40.81% had synchronous malignancies. The median time to the development of second primary malignancy was 60 months. Among the first diagnosed malignancies, cervix was the most common site (26.5%), followed by endometrium (20.4%) and ovary (14.28%), whereas ovarian malignancy was more commonly diagnosed second malignancy (38.77%), followed by endometrium (14.28%) and cervix (10.2%). In an analysis of synchronous malignancies, the most common genital tract involvement was seen with endometrium and ovary, with a predominance of low-grade endometrioid histology in 75% of cases. Conclusions: As the cancer survivor population continues to increase in future, these patients must be comprehensively evaluated on follow-up, and a cognizance of prior treatment taken should be kept. In addition, it is vital that the clinicians keep a lookout for high-risk population in which genetic testing may be beneficial.

Predictive models as a clinical decision support tool for genetic cancer risk assessment among Mexican patients at risk of hereditary colorectal cancer.

10617 Background: Hereditary cancer syndromes, including Lynch syndrome (LS) with an increased risk of colorectal cancer (CRC), have prompted the development of clinical criteria and predictive models (PM) to identify at-risk individuals. However, these criteria have been validated with limited representation from the Latino population. Several factors may influence CRC penetrance, potentially leading to variations in PM performance across populations. Given that CRC ranks as the third most prevalent cancer worldwide, the increasing incidence of early-onset disease highlights the need for expanding Genetic Cancer Risk Assessment (GCRA) services. Methods: This prospective study included Mexican patients who were diagnosed with CRC and met NCCN criteria for GCRA. Participants were enrolled at two referral centers in Mexico, the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City and at the Hospital Zambrano Hellion TecSalud, Nuevo Leon. Participants' carrier risk was estimated using the PREMM5 model. Amsterdam II and revised Bethesda criteria, immunohistochemistry (IHC) for DNA mismatch repair (MMR) proteins in tumor tissue and multigene panel testing results were reviewed. For this analysis, only pathogenic and likely pathogenic (P/LP) variants in probands were reported. Results: From April 2016 to October 2023, 194 patients were included, with a median age at diagnosis of 45.0 (range 17-82) years, and 49.5% were women. P/LP variants were identified in 37.6% (n=73). 27.5% (n=50) were carriers of P/LP variants associated with LS (29 MLH1, 13 MSH2, 6 MSH6, and 2 PMS2). 11.8% (n=23) were carriers of P/LP variants in other genes (7 APC, 4 ATM, 3 CHEK2, 2 BRCA1, 2 TP53, 2 STK11, 1 PALB2, 1 BRIP1, and 1 MUTYH). Overall, carriers of PVs were diagnosed with CRC at a younger age than non-carriers (42 vs 46 years, p=0.034). The Amsterdam II criteria proved to be accurate (Sen 55%, Spe 91%, PPV 0.69, NPV 0.85), while the Bethesda criteria (Sen 98%, Spe 18%, PPV 0.29, NPV 0.96) and IHC for MMR proteins (Sen 94%, Spe 67%, PPV 0.61, NPV 0.95) were found to be highly sensitive. The area under the ROC curve for PREMM5 was 0.82 with a mean score 28.5 (2.1 – 50) in patients with LS and 6.0 (0.9 – 50) in non-carriers. Carriers of PVs had a higher rate of multiple primary malignancies than non-carriers (41.0% vs 19.0%, p=0.0014), and self-reported family history of CRC (65.7% vs 24.8%, p<0.001). Conclusions: Our results showed the PREMM5 model and IHC for MMR proteins effectively prioritized patients eligible for germline genetic testing in resource-limited settings. The performance of PREMM5 in this Mexican cohort was similar to that reported in the validation study of this model in other populations. Considering the spectrum of identified P/LP variants, the multigene panel test should be used in the comprehensive evaluation of Mexican patients with CRC.

316P Primary gallbladder cancer and the risk of gastrointestinal multiple primary malignancies

316P Primary gallbladder cancer and the risk of gastrointestinal multiple primary malignancies

Genetic Predisposition to Sarcoma: What Should Clinicians Know?

Pathogenic germline variants in the setting of several associated cancer predisposition syndromes (CPS) may lead to the development of sarcoma. We would consider testing for a CPS in patients with a strong family history of cancer, multiple primary malignancies, and/or pediatric/adolescent/young adult patients diagnosed with other malignancies strongly associated with CPS. When a CPS is diagnosed in a patient with sarcoma, additional treatment considerations and imaging options for those patients are required. This applies particularly to the use of radiation therapy, ionizing radiation with diagnostic imaging, and the use of alkylating chemotherapy. As data and guidelines are currently lacking for many of these scenarios, we have adopted a shared decision-making process with patients and their families. If the best chance for cure in a patient with CPS requires utilization of radiation therapy or alkylating chemotherapy, we discuss the risks with the patient but do not omit these modalities. However, if there are treatment options that yield equivalent survival rates, yet avoid these modalities, we elect for those options. Considering staging imaging and post-therapy evaluation for sarcoma recurrence, we avoid surveillance techniques that utilize ionizing radiation when possible but do not completely omit them when their use is indicated.

Germline Mutations of Holliday Junction Resolvase Genes in Multiple Primary Malignancies Involving Lung Cancer Lead to PARP Inhibitor Sensitization.

The incidence of multiple primary malignancies (MPM) involving lung cancer has increased in recent decades. There is an urgent need to clarify the genetic profile of such patients and explore more efficacious therapy for them. Peripheral blood samples from MPM involving patients with lung cancer were assessed by whole-exome sequencing (WES), and the identified variants were referenced for pathogenicity using the public available database. Pathway enrichment analysis of mutated genes was performed to identify the most relevant pathway. Next, the effects of mutations in relevant pathway on function and response to targeted drugs were verified by in vitro and in vivo experiments. Germline exomes of 71 patients diagnosed with MPM involving lung cancer were sequenced. Pathway enrichment analysis shows that the homologous recombination repair (HRR) pathway has the strongest correlation. Moreover, HRR genes, especially key Holliday junction resolvases (HJR) genes (GEN1, BLM, SXL4, and RMI1), were most frequently mutated, unlike the status in the samples from patients with lung cancer only. Next, we identified a total of seven mutations in HJR genes led to homologous recombination DNA repair deficiency and rendered lung cancer cells sensitive to PARP inhibitor treatment, both in vitro and in vivo. This is the first study to map the profile of germline mutations in patients with MPM involving lung cancer. This study may shed light on early prevention and novel targeted therapies for MPM involving patients with lung cancer with HJR mutations.

The heterogeneous cancer phenotype of individuals with biallelic germline pathogenic variants in CHEK2

PurposeFemales with biallelic CHEK2 germline pathogenic variants (gPVs) more often develop multiple breast cancers than individuals with monoallelic CHEK2 gPVs. This study is aimed at expanding the knowledge on the occurrence of other malignancies. MethodsExome sequencing of individuals who developed multiple primary malignancies identified 3 individuals with the CHEK2 (NM_007194.4) c.1100del p.(Thr367MetfsTer15) loss-of-function gPV in a biallelic state. We collected the phenotypes of an additional cohort of individuals with CHEK2 biallelic gPVs (n = 291). ResultsIn total, 157 individuals (53.4%; 157/294 individuals) developed ≥1 (pre)malignancy. The most common (pre)malignancies next to breast cancer were colorectal- (n = 19), thyroid- (n = 19), and prostate (pre)malignancies (n = 12). Females with biallelic CHEK2 loss-of-function gPVs more frequently developed ≥2 (pre)malignancies and at an earlier age compared with females biallelic for the CHEK2 c.470T>C p.(Ile157Thr) missense variant. Furthermore, 26 males (31%; 26/84 males) with CHEK2 biallelic gPVs developed ≥1 (pre)malignancies of 15 origins. ConclusionOur study suggests that CHEK2 biallelic gPVs likely increase the susceptibility to develop multiple malignancies in various tissues, both in females and males. However, it is possible that a substantial proportion of individuals with CHEK2 biallelic gPVs is missed as diagnostic testing for CHEK2 often is limited to individuals who developed breast cancer.

Three-year progression-free survival of a patient with concomitant mucinous adenocarcinoma of the colon with peritoneal dissemination and multiple myeloma who received lenalidomide: a case report

BackgroundConcomitant multiple myeloma (MM) and other primary malignancies is rare. Therefore, the treatment outcomes of patients with these conditions have not been well discussed. Lenalidomide is an oral thalidomide analog drug used for MM. Recently, the antitumor effect of lenalidomide has been gaining attention, and lenalidomide has been applied for managing solid tumors. The current case showed the treatment course of a patient treated with lenalidomide for concomitant MM and colon cancer with peritoneal dissemination.Case presentationA 74-year-old female patient receiving treatment for MM was diagnosed with mucinous adenocarcinoma of the transverse colon. The patient was clinically diagnosed with stage IIIC T4aN2M0 disease. Subsequently, laparoscopic colectomy with lymph node dissection was planned. However, intraperitoneal observation revealed peritoneal dissemination that had sporadically and widely spread. Therefore, palliative partial colectomy was performed to prevent future hemorrhage or obstruction. The patient was discharged on the 10th postoperative day without postoperative complication. Based on the patient’s preference, lenalidomide was continually administered for MM without systemic chemotherapy. The patient survived for > 36 months without any signs of tumor progression.ConclusionThe current case first showed the treatment course of concomitant MM and colon cancer. The antitumor effect of lenalidomide can possibly contribute to 3-year progression-free survival in patients with mucinous adenocarcinoma of the colon with peritoneal dissemination.

Field Cancerization in Action; A Case of Synchronous Triple Primary Malignancies in the Head and Neck.

Field cancerization is the phenomenon that classically describes the occurrence of multiple primary malignancies in the head and neck subsites, either synchronous or metachronous. It's unusual to come across synchronous primaries, that too three at a time. Here is a patient who presented to us with triple primary squamous cell carcinomas involving the floor of the mouth, base of the tongue, and glottis at the same time…….

Multiple Primary Malignancies and Bilateral Vocal Cord Paralysis Confusing the Management of Each Other

AbstractDouble primary malignancy though uncommon, we often encounter in our clinical practice. The lung malignancy is known to cause left vocal cord paralysis. Bilateral abductor paralysis secondary to adenocarcinoma of the lung with concurrent basal cell carcinoma of the face is not common. Proper counseling and timely management are needed in these cases of multiple primary malignancies. Early evaluation in all cases of hoarseness can help in early diagnosis and management.

肝癌合并多原发性癌的流行病学与危险因素研究进展

肝癌合并多原发性癌的流行病学与危险因素研究进展

Corrigendum: Risk and prediction of multiple primary malignancies after early gastric cancer

Corrigendum: Risk and prediction of multiple primary malignancies after early gastric cancer

Real-World Treatment Patterns and Outcomes of Patients (Pts) with Follicular Lymphoma (FL) Who Experienced Progression of Disease within 24 Months (POD24)

Introduction: Follicular lymphoma (FL) accounts for about 35% of all non-Hodgkin lymphomas and 70% of indolent lymphomas in the United States. Despite relatively high 1L remission rates, a clinically high-risk subgroup experiences early disease progression within 24 months of 1L initiation (POD24). As the understanding of this population evolves, a treatment paradigm is yet to be established. This study aimed to describe the characteristics of patients who experienced POD24 to 1L therapy and their outcomes following receipt of select 2L treatment sequences using a contemporary real-world (rw) dataset. Methods: Pts meeting the study criteria were identified in the COTA rw database. Eligible pts were aged ≥ 18 years at diagnosis (dx) with grade I-IIIA FL and had no documented grade IIIB or transformation anytime from dx until index date. Pts were treated with 1L CD20+chemotherapy (CHOP/CVP or Benda) and initiated 2L therapy with one of the following treatment categories between January 1, 2010 and December 31, 2019: Benda-CD20, CHOP/CVP-CD20, chemosalvage (e.g., R-ICE), or other novel therapy (e.g., lenalidomide-CD20). Pts were excluded if they were not treated with the specified 1L or 2L therapies, had missing or imprecise key study dates, multiple concurrent primary malignancies at dx, evidence of histologic transformation prior to 2L,1L or 2L clinical trial participation, or documentation of 1L maintenance therapy that did not contain CD20. Characteristics, treatment patterns, and outcomes were analyzed among pts who experienced POD24, defined as documented progression/relapse event within 24 months of 1L initiation. The index date was the date of 2L therapy initiation, and the observation period was defined as the duration of time from index date to the date of death or last visit date (if date of death was not available). Characteristics and treatment patterns were summarized as appropriate using means, medians, and/or counts and percentages. The following rw time to event outcomes were evaluated using the Kaplan-Meier method: time to next treatment (rwTTNT), progression-free survival (rwPFS), and overall survival (rwOS). Rw complete response rate (rwCRR) was calculated as the proportion of pts who achieved a complete response (CR) as the best response to 2L among all POD24 pts. Results: The study included 149 pts who experienced POD24 and met the remaining study criteria. An additional 170 pts (53.3%) qualified for the study but did not experience POD24. The median age at dx for POD24 pts was 61 years. This population was mostly male (57.0%), White (87.9%), and treated in the community practice setting (86.6%). More than 85% of pts had low grade FL at their last assessment at index. Following 1L therapy, 47.0%, 1.3%, 39.6%, and 0.7% of pts had a documented CR, near CR, partial response, or stable disease, respectively. About 11% of pts had progression as their best documented response to 1L. The most common 2L treatment category was Benda+CD20 (47.0%), followed by CHOP/CVP-CD20 (25.5%), chemosalvage (17.4%), and other novel therapies (10.0%). The CD20 received most commonly in 2L was rituximab (87.2%). Of 68 pts who received 3L, 11 (16.2%) received stem cell transplant. Median rwOS from 2L initiation overall was 64.8 months (95% CI: 54.0, 99.6). For pts who received Benda-CD20, CHOP/CVP-CD20, chemosalvage, and other novel therapies in 2L, 5-year rwOS rate from 2L initiation was 49.9%, 52.3%, 57.2%, and 86.2%, respectively. (Table 1) Median rwPFS from 2L initiation overall was 11.3 months, and pts who received Benda-CD20 or other novel therapies in 2L experienced median rwPFS of 25.6 and 18.0 months, respectively, while pts who received CHOP/CVP-CD20 or chemosalvage in 2L experienced median rwPFS of 8.3 and 4.6 months, respectively. (Figure 1) A similar trend was seen in rwTTNT from 2L initiation (overall: 19.6, Benda-CD20: 38.0, CHOP/CVP-CD20: 12.0, chemosalvage: 5.4, and other novel therapies: 19.6 months) and rwCRR for pts who received 2L (overall: 47.7%, Benda-CD20: 57.1%, CHOP/CVP-CD20: 34.2%, chemosalvage: 34.6%, and other novel therapies: 60.0%). Conclusions: Among pts who experienced POD24 and received qualified therapies, 2L outcomes highlight continued unmet need despite recent improvements. Future research is required to identify this subset of high-risk pts at diagnosis and to investigate prospectively the effect of novel therapeutic approaches on their treatment outcomes.

Multiple primary cancers: a case report and literature review

The fortuitous discovery of synchronous double primary cancers of the lung and stomach is relatively rare, but the discovery of triple primary cancers in one patient remains exceptional. The discovery of triple primary cancers in a single patient remains exceptional. This coexistence corresponds to the syndrome of multiple primary malignancies or multiple primary cancers (MPC). We present a case of synchronous association of squamous cell carcinoma of the lung and gastric adenocarcinoma with a history of mature squamous cell carcinoma of the larynx.