Small Cell Carcinoma Component Research Articles

Two Resected Cases of Cholangiocarcinoma with a Small Cell Carcinoma Component

Two Resected Cases of Cholangiocarcinoma with a Small Cell Carcinoma Component

Treatment-Emergent Neuroendocrine Prostate Cancer: A Clinicopathological and Immunohistochemical Analysis of 94 Cases.

PurposeThis study aimed to evaluate the pathological characteristics, immunophenotype, and prognosis of treatment-emergent neuroendocrine prostate cancer (T-NEPC).Materials and MethodsWe collected 231 repeated biopsy specimens of castration-resistant prostate cancer (CRPC) cases between 2008 and 2019. We used histopathological and immunohistochemical evaluations of Synaptophysin (SYN), ChromograninA (CgA), CD56, androgen receptor (AR), and prostate-specific antigen (PSA) to screen out T-NEPC cases. Multivariate analyses were performed to identify factors in the prognosis of T-NEPC. Further, the results were verified in the Surveillance, Epidemiology, and End Results (SEER) program.ResultsAmong the 231 CRPC cases, 94 (40.7%) cases were T-NEPC. T-NEPC were more likely to present with negative immunohistochemistry for AR (30.9%) and PSA (47.9%) than that of CRPC (8.8% and 17.5%, respectively). Kaplan-Meier analysis revealed that patients with T-NEPC (median overall survival [OS]: 17.6 months, 95% CI: 15.3–19.9 months) had significantly worse survival compared with usual CRPC patients (median OS: 23.6 months, 95% CI: 21.3-25.9 months, log-rank P = 0.001), especially in metastasis cases (median OS: 15.7 months, 95% CI: 13.3-18.0 months) and patients with small cell carcinoma component (median OS: 9.7 months, 95% CI: 8.2–11.2 months). Prostate adenocarcinoma with diffuse NE differentiation (median OS: 18.8 months, 95% CI: 15.3–22.3 months) had poor outcome than those with usual CRPC (P = 0.027), while there was no significant change in the focal NE differentiation (median OS: 22.9 months, 95% CI: 18.1–27.7 months, P = 0.136). In the unadjusted model, an excess risk of overall death was observed in T-NEPC with PSA negative (HR = 2.86, 95% CI = 1.39–6.73). Among 476 NEPC cases in the SEER database from 2004 to 2017, we observed a higher hazard of overall death in patients aged 65 years and older (HR = 1.35, 95% CI = 1.08–1.69), patients with PSA ≤ 2.5 ng/ml (HR = 1.90, 95%CI = 1.44–2.52), patients with PSA 2.6–4.0 ng/ml (HR = 2.03, 95%CI = 1.38–2.99), stage IV tumor (HR = 2.13, 95%CI = 1.47–3.08) and other races (HR = 1.85, 95%CI = 1.17–2.94) in total NEPC, adjusting for confounders. Similar hazard ratios were observed in pure NEPC, while there was no significant results among prostate adenocarcinoma with NE differentiation tumors.ConclusionT-NEPC was associated with an unfavorable prognosis, negative immunohistochemistry for PSA in T-NEPC and serum PSA level ≤ 4 ng/ml had a worse prognosis. Urologists and pathologists should recognize the importance of the second biopsy in CRPC to avoid unnecessary diagnosis and treatment delays.

P01 An Unusual Case of Pseudomesotheliomatous Carcinoma of the Lung

Pseudomesotheliomatous carcinoma of the lung is a rare entity. It has been known to mimic malignant pleural mesothelioma, clinically and pathologically. This often poses a challenge to clinicians and pathologists. We present a case of pseudomesotheliomatous carcinoma consisting of three different distinct components: namely adenocarcinoma, small cell carcinoma and sarcomatoid carcinoma components.

Composite tumor of the larynx: A Case Report

Composite tumor of larynx, a recently included entity in the current WHO classification, is often a difficult pathological diagnosis, especially in small biopsies. We report a case of laryngeal composite tumor, initially misdiagnosed as squamous cell carcinoma, which later turned out to be composite in nature, with associated neuroendocrine (small cell carcinoma) component. This report emphasizes the need for obtaining deeper biopsies and their thorough pathological examination to improve the diagnostic accuracy. Keywords: combined small cell carcinoma; composite tumor; larynx; small cell carcinoma; squamous cell carcinoma.

Rebiopsy in patients with or without prior TKIs revealed complicated histology of lung cancer.

e20525 Background: The important of rebiopsy is well known in lung adenocarcinomas (ADs) after acquiring resistant to TKIs, for they may transform to SCLC. But histology transformation in non-ADs or ADs without TKIs seems infrequent. Methods: We performed a retrospective collection of cases with changed histology after rebiopsy in patients presenting from January 2015 to April 2018 in a single center. Results: Among 188 patients who conducted rebiopsy, there were 20 cases presenting changed histologic type, which can be divided into two groups based on if TKIs were used before histology change. Group1 (TKIs used, N = 14) including ADs changing to SCLC (N = 9), squamous cell carcinoma (SQ) (N = 2), carcinosarcoma combined with few AD component (N = 1), SCLC combined AD (N = 1), and adenosquamous carcinoma changing to SCLC (N = 1). Four cases in group 1 went through surgery, and one of them who never smoke was diagnosed as AD (pT2N0M1a, EGFR exon 19del), with no small cell carcinoma (SCC) component found, but rebiopsy of metastasis revealed SCC without any AD component after 3 months of gefitinib. The disease continued to progress during the following chemotherapy (CT), and biopsies with other two metastases also presented SCC without AD component. Group 2 were 6 cases without TKIs before the rebiopsy (Table). Case 2, 4, 6 were all heavy smokers. Rebiopsy of case 2 was ALK+, so the patient took 4 months crizotinib and then 2 months alectinib, the disease was still stable on January 6, 2019. Case 5 was a classic extensive-stage SCLC with fast response to EP therapy, but fast relapse and resistance to the following CT, and the primary lesion at right upper lobe showed AD-like imaging, so rebiopsy was performed and carcinoma favor AD was found. EGFR exon 19del was detected in the plasma, and the lesion gain PR after one month of icotinib. The third biopsy of the progress lesion came back to SCC after resistance to TKI. Conclusions: Rebiopsy of lung cancers with or without TKIs therapy revealed diversity histology changes. This reminded us the important of rebiopsy, not only for TKIs resistant lung ADs. [Table: see text]

A rare case of bipartite combined tumour of the oesophagus

BackgroundBipartite combined oesophageal tumours are an exceedingly rare entity and much less is known about the natural history of these tumours following curative surgery. The authors present a case of a bipartite combined oesophageal tumour comprising of sarcomatoid carcinoma and small cell carcinoma with early postoperative recurrence.Case presentationA 63-year-old Chinese male with a smoking history presents with hemoptysis on a background of dysphagia and odynophagia for 1 month. An endoscopic evaluation found an exophytic oesophageal tumour with contact bleeding for which biopsy of this lesion returned as a malignant high-grade tumour where immunohistochemistry staining was unable to establish the lineage of the tumour. Differential diagnoses include sarcomatoid carcinoma and malignant undifferentiated sarcoma. With the provisional diagnosis of a high-grade oesopheageal sarcoma, the patient underwent minimally invasive McKeown’s oesophagectomy. Final histological assessment was pT1bN0 with two histological types of malignancy within a single tumour—70% poorly differentiated spindle cell squamous carcinoma and small cell carcinoma. He was planned for adjuvant chemotherapy in view of the small cell carcinoma component after the resolution of the postoperative infective collections. A computed tomographic scan performed 4 months postoperatively demonstrated metastasis to the lung, pleura, thoracic nodes and liver. Biopsy of the largest lung nodule confirmed small cell neuroendocrine carcinoma with features similar to the small cell carcinoma component in the prior oesophagectomy specimen. He was thereafter initiated on palliative chemotherapy aimed at three weekly carboplatin and etoposide aimed at a total of 4 cycles with peglasta support. Etoposide was stopped during the first cycle due to asymptomatic bradycardia. The regime was then converted to carboplatin with irinotecan for 5 cycles. Repeat computed tomographic scan performed 3 weeks after the completion of chemotherapy showed a complete response of lung and liver metastasis and no evidence of local recurrence or distant metastasis.ConclusionThe management of bipartite combined oesophageal tumours should be guided by its more aggressive component. Bipartite combined oesophageal tumours with a small cell carcinoma component are believed to demonstrate aggressive tumour biology likened to that of primary oesophageal small cell carcinoma. Preoperative confirmation of a combined tumour may be challenging, and biopsy results may only yield one of the two components. The more aggressive component is usually a small cell carcinoma, for which the mainstay of therapy is platinum-based chemotherapy rather than surgery.

Cytopathologic characteristics of HPV-related small cell carcinoma of the oropharynx.

Human papillomavirus (HPV)-related squamous cell carcinoma (SqCC) of the oropharynx is an epidemiologically and clinically distinct form of SqCC that is associated with an improved prognosis. However, HPV-related small cell carcinoma of the oropharynx is a rare and newly described variant that is associated with aggressive clinical behavior and poor outcomes. To date, fewer than 2 dozen reports of this entity exist in the literature, and there is no discussion of cytopathologic features. This article reports 6 cases and discusses the salient cytomorphologic findings, ancillary studies, and challenges when this entity is encountered. Anatomic pathology archives were searched to identify patients with a diagnosis of HPV-related small cell carcinoma of the oropharynx. Medical records were reviewed to document the following: age, sex, smoking status, other relevant clinical history, primary location, treatment, and clinical outcome. Both p16 and high-risk HPV in situ hybridization (ISH) studies were positive in at least 1 specimen from each patient. The pathologic diagnoses, cytomorphologic characteristics, immunocytochemical stains, and HPV ISH studies were reviewed and recorded for all available cases. Six patients with 11 cytopathology specimens of HPV-related small cell carcinoma of the oropharynx were identified. The mean age was 61.3 years, and all patients died with widely metastatic disease (mean, 23 months; range, 12-48 months). Mixed small cell carcinoma and SqCC components were present in half of the cases. The identification of a small cell component can be reliably performed with cytology preparations and is crucial because this (and not the HPV status) determines the prognosis.

SMALL CELL PROSTATE CANCER PRODUCING SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONE; A CASE REPORT

A 73-year-old man with progressive prostate cancer visited our hospital after prostate biopsy performed at another hospital. His serum PSA level was 29.02 ng/ml. CT revealed invasion of the bladder, bilateral ureters, and rectum. Otherwise, there was no evidence of metastasis. Pathological findings showed a poorly differentiated adenocarcinoma (Gleason score 4+5) and small cell carcinoma component. Two months after administering combined androgen blockade therapy, he was admitted due to severe hyponatremia caused by the inappropriate secretion of antidiuretic hormone. Furthermore, CT revealed right ureter metastasis, although the PSA levels remained low. Therefore, the patient was put on fluid restriction and sodium administration. After the patient recovered from hyponatremia, chemotherapy, including VP-16 and CDDP, was initiated. However, CT after two chemotherapy cycles revealed disease progression, with multiple bone metastases. Second-line chemotherapy, including CPT-11 and CDDP, was less effective, and the patient died 9 months after the diagnosis.

Characterization of a splice-site mutation in the tumor suppressor gene FLCN associated with renal cancer

BackgroundRenal cell carcinoma is among the most prevalent malignancies. It is generally sporadic. However, genetic studies of rare familial forms have led to the identification of mutations in causative genes such as VHL and FLCN. Mutations in the FLCN gene are the cause of Birt-Hogg-Dubé syndrome, a rare tumor syndrome which is characterized by the combination of renal cell carcinoma, pneumothorax and skin tumors.MethodsUsing Sanger sequencing we identify a heterozygous splice-site mutation in FLCN in lymphocyte DNA of a patient suffering from renal cell carcinoma. Furthermore, both tumor DNA and DNA from a metastasis are analyzed regarding this mutation. The pathogenic effect of the sequence alteration is confirmed by minigene assays and the biochemical consequences on the protein are examined using TALEN-mediated transgenesis in cultured cells.ResultsHere we describe an FLCN mutation in a 55-year-old patient who presented himself with progressive weight loss, bilateral kidney cysts and renal tumors. He and members of his family had a history of recurrent pneumothorax during the last few decades. Histology after tumor nephrectomy showed a mixed kidney cancer consisting of elements of a chromophobe renal cell carcinoma and dedifferentiated small cell carcinoma component. Subsequent FLCN sequencing identified an intronic c.1177-5_-3delCTC alteration that most likely affected the correct splicing of exon 11 of the FLCN gene. We demonstrate skipping of exon 11 to be the consequence of this mutation leading to a shift in the reading frame and the insertion of a premature stop codon. Interestingly, the truncated protein was still expressed both in cell culture and in tumor tissue, though it was strongly destabilized and its subcellular localization differed from wild-type FLCN. Both, altered protein stability and subcellular localization could be partly reversed by blocking proteasomal and lysosomal degradation.ConclusionsIdentification of disease-causing mutations in BHD syndrome requires the analysis of intronic sequences. However, biochemical validation of the consecutive alterations of the resulting protein is especially important in these cases. Functional characterization of the disease-causing mutations in BHD syndrome may guide further research for the development of novel diagnostic and therapeutic strategies.

Clinical analysis of small cell carcinoma of the bladder in Chinese: nine case reports and literature reviews

BackgroundSmall cell carcinoma of the bladder (SCCB) is a kind of rare and highly aggressive tumor that is present in an advanced stage and has a propensity for early metastasis. The main presenting symptom of SCCB is hematuria. Surgery, chemotherapy, and radiotherapy, either alone or as a part of combined therapy, have been used as the treatment. The aim of this study is to present our experience with 9 SCCB patients who were treated with different modalities and to share the findings upon reviewing the literatures for patients with SCCB reported in 56 literatures in Chinese.MethodsWe retrospectively evaluated 9 patients with SCCB from February 1980 to January 2014 in Tongji Hospital, Huazhong University of Science and Technology. The general characteristics, clinical manifestations, the pathological and immunohistochemical characteristics, treatment options, and prognostication in those eligible manuscripts were analyzed. In order to gain a better understanding of the clinical features of SCCB, another 119 cases reported in 56 articles were reviewed together (from January 1979 to March 2014). And a retrospective analysis was performed.ResultsAll the 9 cases in Tongji Hospital were successfully operated, and the tissue samples were sent for pathological examination. All the tumor tissues contained small cell carcinoma components. 4 cases coexisted with other histologic types of bladder cancers, and 2 out of the 9 cases had three different cell components. All the patients had muscle invasion, and 4 cases showed lymph nodes metastasis, 3 cases showed invasion of neighboring structures (seminal vesicle or uterus), and 1 case was highly suspected of liver metastasis. Immunohistochemistry results showed that PCK, Syn, NSE, and CD56 were all positive, but LCA was negative. After operations, 3 patients underwent chemotherapy and only 1 patient received postoperative radiotherapy. Patients were followed up, ranging from 3 to 84 months and the median survival time was 33 months. The leading cause of death was tumor recurrence or metastasis, while 2 patients are still alive. According to the published literature, the pathological stage, immunohistochemical markers, and survival curves of all the 128 cases were also retrospectively analyzed.ConclusionsSCCB is different from transitional cell carcinoma (TCC) of the bladder. It has its unique cytology, immunohistochemistry, and ultrastructural features. Its diagnosis relies on pathological examination and immunohistochemistry. The current main treatment for SCCB is surgery combined with chemotherapy. Since the disease develops early metastasis easily, the overall prognosis of this cancer is poor. Further research need to clarify the molecular pathogenesis so that novel therapies can be developed for this rare cancer.

混合型子宮頸癌 (腺癌, 小細胞癌) の 1 例

混合型子宮頸癌 (腺癌, 小細胞癌) の 1 例

Mixed adenoneuroendocrine carcinoma of the ampulla of Vater: A case report.

Mixed adenoneuroendocrine carcinomas (MANECs) are rare biphasic tumour types, which are morphologically recognisable as both gland-forming and neuroendocrine neoplasms. Within the gastrointestinal tract, MANECs occur predominantly in the stomach or colorectum. The present study described a case of a MANEC originating from the ampullary region. The patient presented with widespread metastatic disease. Biopsy samples obtained from the ampullary primary tumour disclosed a complex lesion with adenocarcinoma and neuroendocrine small cell carcinoma components, positive for the intestinal transcription factor caudal type homeobox-2 and for neuroendocrine markers, including chromogranin A, synaptophysin, cluster of differentiation 56/neural cell adhesion molecule. By contrast, biopsy samples obtained from metastatic tissue revealed pure neuroendocrine carcinoma. As exemplified by this true mixed tumour, tumour heterogeneity evolves as the major challenge in oncology today, with potentially severe implications for the choice of chemotherapy. The assessment of metastatic sites may render valuable diagnostic information that is crucial for clinical decision-making and patient management.

Small Cell Carcinomas of the Bladder Highly Express Somatostatin Receptor Type 2A: Impact on Prognosis and Treatment--A Multicenter Study of Urooncology Society, Turkey.

Small cell carcinoma (SmCC) is a rare and aggressive neuroendocrine carcinoma of the bladder. Neuroendocrine carcinomas expressing somatostatin receptors (SSTR) in other viscera such as lung, pancreas, and gastrointestinal system respond to therapy with somatostatin analogs. In the present study, expressions of SSTRs 1 to 5 including type 2A are investigated by immunohistochemistry (IHC) and their relationship with clinicopathologic factors was evaluated. Hundred primary bladder SmCC cases were collected from 12 centers in Turkey. Forty-three cases were pure SmCC. Other cases had mostly papillary urothelial carcinoma as a second component. The percentage of the SmCC component ranged from 5% to 100%. SSTR-2A expression was membranous, whereas the other receptors showed cytoplasmic staining. The percentages of positive cases for SSTR-1, SSTR-2A, SSTR-3, SSTR-4, and SSTR-5 were 4% (3/75), 61.4% (54/88), 2.4% (2/84), 24.4% (20/82), and 6.25% (5/80), respectively. The percentage of SmCC component was positively correlated with the percentage of SSTR-2A expression (P=0.003) while negatively correlated with patient age (P=0.032). SSTR-2A expression was correlated with survival as a bad prognostic factor (P=0.018). SSTR-1, SSTR-3, SSTR-4, and SSTR-5 expressions did not show any statistical significance with any parameter. In conclusion, although the limited number of cases with adequate term follow-up, SSTR-2A expression could be a prognostic factor and somatostatin analogs therapeutic candidate for SmCCs of the bladder as these tumors show high percentage of SSTR-2A expression.

Abstract A28: N-Myc drives small cell neuroendocrine cancer initiated from human prostate basal cells

Abstract Human small cell prostate carcinoma (SCPC) represents up to 25% of lethal castration-resistant prostate cancer. Molecular characterization of a panel of SCPCs recently identified frequent genomic amplification of both MYCN and AURKA. The oncogenic function of N-Myc has been characterized in many cancer types but its role in the initiation of human SCPC has not been defined. To investigate the function of N-Myc in human prostate transformation, we utilized a tissue regeneration model of human prostate cancer. Human prostate basal epithelial cells were isolated from benign primary prostate tissue from four independent human donors, infected with lentiviruses expressing the oncogenes N-Myc and activated (myristoylated) AKT1, mixed with mouse urogenital sinus mesenchyme, and grafted subcutaneously in immunodeficient NOD-SCID-IL2Rγnull mice. Palpable tumors were appreciated within 2-3 months and histological evaluation revealed regions of mixed high-grade adenocarcinoma and small cell carcinoma. The small cell carcinoma histology showed typical findings of high nuclear-to-cytoplasmic ratio, nuclear molding, stippled chromatin, and frequent mitotic and apoptotic features. Immunohistochemical analysis demonstrated low to absent androgen receptor (AR) staining in both the adenocarcinoma and small cell carcinoma. Further, we found heterogeneous staining for neuroendocrine markers including neural cell adhesion molecule 1, chromogranin A, synaptophysin, thyroid transcription factor 1, and forkhead box A2 in the regions of small cell carcinoma in support of the histological diagnosis. To assess the androgen dependence of tumor growth, regenerated N-Myc and activated AKT1 tumors derived from the lentiviral infection of primary human prostate basal cells were passaged in either intact or castrate immunodeficient mice. Tumors were propagated both in the presence and absence of androgens and showed a small but progressive enrichment of the small cell carcinoma over the adenocarcinoma with successive passage in castrate hosts. Molecular profiling by RNA-Seq of three regenerated N-Myc and activated AKT1 tumors showed a significant resemblance to a subset of human SCPC clinical specimens. Further, the adenocarcinoma and small cell carcinoma components of each tumor were remarkably similar at the transcriptional level despite their differences in histological appearance. In conclusion, we have established a novel model of human small cell prostate cancer arising from benign human prostate basal cells. Overexpression of N-Myc and activated AKT1 in basal cells produces tumors that recapitulate the histology, immunophenotype, and transcriptional profile of human SCPC. These findings support a direct role for N-Myc in the neuroendocrine transformation of basal cells in the human prostate. Further studies are ongoing to elucidate the mechanisms by which N-Myc induces a neuroendocrine differentiation program in prostate cancer. Citation Format: John K. Lee, Bryan A. Smith, John W. Phillips, Jungwook Park, Tanya I. Stoyanova, Robert Baertsch, Artem Sokolov, Colleen Mathis, Donghui Cheng, Joshua M. Stuart, Jiaoti Huang, Owen N. Witte. N-Myc drives small cell neuroendocrine cancer initiated from human prostate basal cells. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A28.

Primary small cell carcinoma of urinary bladder

Primary pure small cell carcinoma of the urinary bladder is an extremely rare and highly aggressive tumor with an average five-year survival rate of less than 10% as cited by multiple case reports. It accounts for about 0.5-1% of all bladder tumors. We present the case of an 87-years-old man; smoker hospitalized in the Department of Urology, from the Institute of Medicine, Kathmandu for intermittent painless hematuria. Ultrasonography showed a sessile tumoral growth. Transurethral resection of the tumor mass was performed and tissue fragments were sent to the pathologic lab to establish the histologic type, the degree of differentiation and invasion. Fragments of the tumor were fixed in 10% formaldehyde, paraffin embedded and processed as standard technique; the sections were stained with H and E and immunohistochemically with NSE and Cytokeratin. A diagnosis of small cell carcinoma was established. Because of aggressive behavior and distinct treatment, the pathologist should watch out for the presence of small cell carcinoma component.

Integrative molecular profiling of routine clinical prostate cancer specimens

Comprehensive molecular profiling led to the recognition of multiple prostate cancer (PCa) molecular subtypes and driving alterations, but translating these findings to clinical practice is challenging. We developed a formalin-fixed paraffin-embedded (FFPE) tissue compatible integrative assay for PCa molecular subtyping and interrogation of relevant genetic/transcriptomic alterations (MiPC). We applied MiPC, which combines capture-based next generation sequencing and quantitative reverse transcription PCR (qRT-PCR), to 53 FFPE PCa specimens representing cases not well represented in frozen tissue cohorts, including 8 paired primary tumor and lymph node metastases. Results were validated using multiplexed PCR based NGS and Sanger sequencing. We identified known and novel potential driving, somatic mutations and copy number alterations, including a novel BRAF T599_V600insHT mutation and CYP11B2 amplification in a patient treated with ketoconazole (a potent CYP11B2 inhibitor). qRT-PCR integration enabled comprehensive molecular subtyping and provided complementary information, such as androgen receptor (AR) target gene module assessment in advanced cases and SPINK1 over-expression. MiPC identified highly concordant profiles for all 8 tumor/lymph node metastasis pairs, consistent with limited heterogeneity amongst driving events. MiPC and exome sequencing were performed on separately isolated conventional acinar PCa and prostatic small cell carcinoma (SCC) components from the same FFPE resection specimen to enable direct comparison of histologically distinct components. While both components showed TMPRSS2:ERG fusions, the SCC component exclusively harbored complete TP53 inactivation (frameshift variant and copy loss) and two CREBBP mutations. Our results demonstrate the feasibility of integrative profiling of routine PCa specimens, which may have utility for understanding disease biology and enabling personalized medicine applications.

Surgical resection for a second primary lung cancer originating close to the initial surgical margin for lung squamous cell carcinoma.

Few reports have described surgical resection for second primary lung cancers originating close to the initial surgical margin for lung cancer. A 64-year-old man had undergone left segmentectomy with lymph node dissection for small peripheral squamous cell lung cancer using video-assisted thoracic surgery, with pathology confirming a small tumor 12 mm in diameter identified about 3 cm from the surgical margin. Eighteen months after initial surgery, computed tomography revealed a 30 mm pulmonary nodule close to the initial surgical margin in the residual left upper lobe and the serum level of carcinoembryonic antigen was found to be increased. Local recurrence on the staple-line of the surgical margin was suspected, and completion left upper lobectomy was performed. Histological examination identified not only a squamous cell carcinoma component but also a small cell carcinoma component. The immunohistochemical staining pattern of the second tumor differed from that of the initial resected lung squamous cell carcinoma. The final pathological diagnosis was a second primary tumor with mixed small cell carcinoma and squamous cell carcinoma histology.

Immunohistochemical survey of mismatch repair protein expression in uterine sarcomas and carcinosarcomas.

Uterine sarcomas and carcinosarcomas are an aggressive group of uterine malignancies. The frequency of mismatch repair (MMR) protein loss by immunohistochemical evaluation has not been comprehensively characterized in this group of tumors; hence, the appropriateness of applying an immunohistochemical panel to screen for Lynch syndrome in these tumors remains unclear. We examined for the immunohistochemical loss of 4 MMR proteins (MLH1, MSH2, MSH6, and PMS2) in a series of 67 uterine carcinosarcomas and 51 uterine sarcomas (20 leiomyosarcomas, 11 adenosarcomas, 9 low-grade endometrial stromal sarcomas, 8 high-grade endometrial stromal sarcomas/undifferentiated endometrial sarcomas, and 3 rhabdomyosarcomas) at our institution. Four of the 67 (6.0%) carcinosarcomas demonstrated abnormal MMR protein expression. Two tumors showed concurrent loss of MLH1 and PMS2 in both the carcinomatous and sarcomatous components. One tumor showed the loss of only PMS2 in both components. The remaining tumor showed an isolated loss of MLH1 and PMS2 in only the small cell carcinoma component, whereas the non-small-cell carcinoma and sarcoma components demonstrated normal staining patterns for MMR proteins. Two of 20 leiomyosarcomas (10%) showed the loss of MMR proteins: one with loss of PMS2 and the other with loss of MSH2 and MSH6. All other uterine sarcoma types examined showed intact MMR protein expression. These observations provide a basis for MMR protein screening in uterine carcinosarcomas and leiomyosarcomas but not in other types of uterine mesenchymal or mixed epithelial/mesenchymal malignancies.

Small cell carcinoma of the prostate: Three case reports and a literature review

Small cell carcinoma (SCC) of the prostate is a high-grade malignant neoplasm with neuroendocrine differentiation and accounts for only 0.5–2% of all prostate cancers. From 2005 to 2010, there were a total of three cases of SCC at our hospital. The disease onset age was 61, 74, and 84 years, respectively. Initial presentations include urinary difficulty, bone pain, and gross hematuria. One patient had mixed tumors of both SCC and adenocarcinoma, and two had prior adenocarcinomas that recurred as SCC. The diagnosis of SCC was all made via transurethral resection. Two patients died of their diseases 7 and 15 months after diagnosis, and one survived for more than 65 months. The serum prostate specific antigen (PSA) was 1660 ng/mL, 72.8 ng/mL, and 35.7 ng/mL before definitive diagnosis. Notably, the only surviving patient was diagnosed with SCC after the transurethral resection of prostate because of the presence of lower urinary tract symptoms. The serum PSA prior to the operation was 0.11 ng/mL, and he received chemotherapy with 5 courses of cisplatin and VP-16. Palliative transurethral resection of the prostate (TURP) not only solved the obstructive symptoms of voiding but helped in removing the prostate tissue, which might have the SCC component in patients with prostate adenocarcinoma under androgen deprivation therapy.

Highly aggressive human papillomavirus-related oropharyngeal cancer: clinical, radiologic, and pathologic characteristics

Although the majority of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas have a favorable prognosis, we search for markers of poor prognosis by carefully examining a subset of highly aggressive cases. Seven patients with HPV-positive oropharyngeal cancer who presented with non-pulmonary distant metastasis or developed distant metastasis posttreatment were identified. Eight control cases were chosen which responded well to treatment. Pathologic and radiologic studies were reviewed and compared. Two cases displayed a small cell carcinoma (SmCC) component upon pathologic review. Biomarker analysis revealed lower expression of NOTCH1 in the aggressive cohort in comparison to controls (P = .04). Cases showed a predominance of clustering of lymph nodes, extracapsular spread, and central tumor necrosis. Although most HPV-related oropharyngeal cancers display a positive prognosis, it is evident that there is a subset, which behaves more aggressively. This early investigation identifies pathologic and radiologic features that may help to predict this behavior.