Five Cases Report of Solid Tumor Synchronously with Hematologic Malignancy

The reported incidence of synchronous multiple primary cancer (SMPC) is rare, and it is even less common to observe synchronous solid tumor with a hematological malignancy. We report five cases of solid tumor presented synchronously with hematological malignancy, all observed within a 2 year period at the oncology department of a university hospital in Shanghai, China. These individual cases included lung adenocarcinoma with chronic myelogenous leukemia, colon cancer with solitary plasmocytoma, gastric adenocarcinoma with diffuse large B cell non-Hodgkin's lymphoma, lung adenocarcinoma with multiple myeloma, and colon cancer with diffuse large B cell non-Hodgkin's lymphoma. It is challenging to therapeutically control the biological behavior of concurrent multiple primary tumors, and there is no standard treatment for such rare conditions. In this paper we discuss these five cases of SMPC and their treatments

Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma

Lineage transition in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of non-small cell lung cancer, as implicated by clinical observation of mixed ADC and SCC pathologies in adenosquamous cell carcinoma, remains a fundamental yet unsolved question. Here we provide in vivo evidence showing the transdifferentiation of lung cancer from ADC to SCC in mice: Lkb1-deficient lung ADC progressively transdifferentiates into SCC, via a pathologically mixed mAd-SCC intermediate. We find that reduction of lysyl oxidase (Lox) in Lkb1-deficient lung ADC decreases collagen disposition and triggers extracellular matrix remodelling and upregulates p63 expression, a SCC lineage survival oncogene. Pharmacological Lox inhibition promotes the transdifferentiation, whereas ectopic Lox expression significantly inhibits this process. Notably, ADC and SCC show differential responses to Lox inhibition. Collectively, our findings demonstrate the de novo transdifferentiation of lung ADC to SCC in mice and provide mechanistic insight that may have important implications for lung cancer treatment

The need for bone biopsies in the diagnosis of new bone lesions in patients with a known primary malignancy: A comparative review of 117 biopsy cases

Objective: This study used a clinical dataset to investigate the proportion of the newly found bone lesions in malignant patients diagnosed by biopsy as being benign, malignant but unrelated to the primary malignancy, or bone metastases of the primary malignancy. The clinical factors that might affect the correlation between bone lesions and the primary malignancy were also analyzed. It is expected to obtain some information contributing to the clinical decision-making regarding the need for biopsy of these lesions from the research results. Methods: Data from patients with a single known malignant tumor who had undergone biopsy of newly found bone lesions at our research institution between January 2012 and December 2017 were reviewed. Based on the pathology results, included cases were divided into a bone-metastasis-of-primary-tumor group (Group 1) and a non-bone-metastasis-of-primary-tumor group (Group 2). The sex, age, diagnostic interval time between the primary malignancy and bone lesions, clinical symptoms, number of involved bones, sites of bone biopsy, and 18F-FDG PET/CT results were compared between groups. Results: A total of 117 patients (92 in Group 1 and 25 in Group 2) were included in the study. There was no significant difference in the sex, age or diagnostic interval time between patient groups. Of all the cases, 17.9% (21/117) were identified to be benign lesions such as fibrous dysplasia (n = 2), bone tuberculosis (n = 1), simple bone cyst (n = 1), aneurysmal bone cyst (n = 1), or solitary fibrous tumor (n = 1). Meanwhile, 3.4% (4/117) were new malignancies including chondrosarcoma (n = 1), plasmacytoma (n = 1) and bone metastases unrelated to the primary malignancy (n = 2). Bone metastases pertinent to the primary tumor accounted for 78.6% (92/117) of cases. Liver (n = 18), kidney (n = 14), breast (n = 13) and lung (n = 12) were the most common cancers among cases. Cases with clinical symptoms exhibited a higher likelihood of their bone lesions being diagnosed as bone metastases of their primary malignancy than those without clinical symptoms (81.3% (87/107) vs. 50.0% (5/10)) (P = 0.021). Neither the number of bone lesions nor the biopsy sites appeared to influence whether the bone lesions were metastases of the primary malignancy or not. In PET/CT examination, the mean maximum standardized uptake values of the two groups were similar. Conclusions: This study indicated that more than 1/5 of newly identified bone lesions in patients with a single known malignancy were not clinically associated with their primary tumors. Furthermore, 3.4% of these were newly discovered malignant bone tumors. The presence of clinical symptoms may be a significant factor affecting whether a new bone lesion is clinically linked to a patient's primary malignancy. Based on the experience from these patients, as for the newly found bone lesions, it is worthy to perform an active biopsy on those asymptomatic ones to avoid misdiagnosis and less biopsy on symptomatic ones for the sake of less cost and risks. Keywords: Bone neoplasms, Neoplasm metastasis, Biops

A rare case of watery diarrhea, hypokalemia and achlorhydria syndrome caused by pheochromocytoma

BACKGROUND: A rare syndrome of watery diarrhea, hypokalemia and achlorhydria (WDHA) is usually caused by pancreatic endocrine tumors that secrete excessive vasoactive intestinal polypeptide (VIP). Here we report a rare case of WDHA caused by a pheochromocytoma. CASE PRESENTATION: A 45-year old male presented with persistent and progressive watery diarrhea for half a year, and was treated with dialysis due to azotemia, hypokalemia, hypercalcemia and metabolic acidosis. A right adrenal mass was found by ultrasonography, and Positron Emission Tomography-Computed Tomography (PET-CT) showed the tumor was hyper-metabolic. Levels of plasma normetanephrine (NMN) and serum chromogranin A (CgA) were significantly elevated. Immunohistochemistry analysis of the adrenal tumor was strongly positive for CgA, synaptophysin and VIP. The patient fully recovered from WDHA syndrome soon after surgery, as reflected in that diarrhea stopped, levels of plasma NMN, serum CgA, and electrolytes returned to normal thus no dialysis was needed. The patient remained disease free in a 12-months follow-up period. CONCLUSION: We report an extremely rare case of pheochromocytoma causing WDHA syndrome and uremia, which the patient completely recovered from after tumor resection

Primary Salivary Gland–Type Lung Cancer: Clinicopathological Analysis of 88 Cases from China

Introduction:Salivary gland–type cancers are rare lung neoplasms involving mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (ACC), and epithelial–myoepithelial carcinoma (EMC). Their behavior and prognostic features are not clearly defined because of their low incidence. We retrospectively analyzed the clinicopathologic profiles of these tumors in a large series.Methods:Eighty-eight patients confirmed as having primary salivary gland–type lung cancer between May 2001 and January 2013 were included from the archives of two thoracic oncology center institutions in China and retrospectively evaluated.Results:Of the total 88 patients, 69 were MEC, 12 ACC, and seven EMC. Overall survival (OS) at 3, 5, and 10 years was 91.3%, 86%, and 80.6% in all cases, respectively, and disease-free survival (DFS) was 90.1%, 78.6%, and 55%, respectively. No significant difference was found among MEC, ACC, and EMC groups regarding OS (p = 0.518) and DFS (p = 0.082). Tumor-node-metastasis stage, lymph node involvement, intrathoracic invasion, and margin status were found to be related with OS (p = 0.000, 0.029, 0.000, 0.004) and DFS (p = 0.018, 0.042, 0.002, 0.002). Intrathoracic invasion was an independent predictor for OS (hazard ratio [HR], 1.129; p = 0.039) and DFS (HR, 1.071; p = 0.011). For patients with MEC, pathological grade also was an independent predictor of OS (HR, 0.045; p = 0.006) and DFS (HR, 0.067; p = 0.001).Conclusions:Salivary gland–type lung cancers are a group of low-aggressive entities with higher tendency to recurrence/metastasis. Intensive clinical, radiological, and pathological examinations are essential to estimation of the risk stratification and management

Tumor containing fragment number influences immunohistochemistry positive rate of HER2 in biopsy specimens of gastric cancer

Abstract Background HER2 assessment in biopsy specimens of gastric cancer (GC) is challenging because of the intratumoral heterogeneity. False negative results may be get because of limited biopsy material. The aim of this study is to explore how tumor-containing fragment number and biopsy specimen number affect HER2 immunohistochemistry (IHC) positive rate. Methods Eight hundred and ninety biopsy specimens and 459 paired resected specimens were collected. IHC staining of HER2 was performed. HER2 IHC positive (scored 3+) rate was compared based on tumor-containing fragment number, biopsy specimen number, average size and tumor tissue proportion of tumor-containing fragments. The positive predictability of biopsy specimens to resected specimens was analyzed based on tumor fragment number. Results HER2 IHC positive rates were 2.0, 3.5, 7.0, 13.2, 17.1, and 15.9% when tumor fragment numbers were 1, 2, 3, 4, 5 and 6 respectively. The rate rose with the increase of tumor fragment number (P = 0.004). ROC curve analysis showed that biopsy specimens exhibited positive predictability when tumor fragment number reached 3, but showed better performance when the number was ≥4 (P  0.05). HER2 IHC positive rate was not associated with biopsy number (P = 0.127), average size of tumor fragments (P = 0.397), and tumor tissue proportion of tumor fragments (P = 0.825) directly. Conclusions The number of tumor-containing fragments influences HER2 IHC positive (scored 3+) rate. Greater than or equal to 4 (≥4) tumor fragments give better results in the positive rate as well as positive predictability. We recommend the number of tumor containing fragments be described in the HER2 IHC pathology reports for clinical reference in endoscopic biopsy specimens of GC

MAML2 rearrangement in primary pulmonary mucoepidermoid carcinoma and the correlation with FLT1 expression.

INTRODUCTION: Primary pulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19) resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied. METHODS: We detected MAML2 rearrangement using fluorescence in situ hybridization (FISH) in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC), and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC). The findings were then examined regarding the clinicopathological parameters and patient outcomes. RESULTS: FISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; p = 0.001) and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p<0.001 and p = 0.023, respectively). Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (p = 0.023) or disease-free survival (p = 0.027) as well as correlation between FLT1 and overall survival (p = 0.009). CONCLUSIONS: MAML2 rearrangement appears frequent in PMEC and specific with this tumor. Both the presence of MAML2 rearrangement and absence of FLT1 tend to confer a favorable clinical outcome. These findings suggest that molecular detection of MAML2 rearrangement combined with FLT1 may be of important clinical value for PMEC