Başak DOĞANAVŞARGİL, Fatma YILDIRIM ÜNAL, Murat SEZAK, BANU YAMAN, Müge TUNÇYÜREK

Kolorektal medüller karsinom tanısına histopatolojik yaklaşım ve klinikopatolojik önemi

Giriş ve Amaç: Medüller karsinomlar, tüm kolorektal kanserlerin %1’inden azını oluşturan, histolojik olarak geniş eozinofilik sitoplazmalı, veziküler nükleuslu ve belirgin nükleollü hücrelerle karakterli glandüler diferansiyasyonun gözlenmediği, solid büyüme paternine sahip nadir tümörler olup, yüksek mikrosatellit instabilite ve Lynch sendromu ile olan ilişkisi nedeniyle önemli antitelerdir. Çalışmamızda medüller karsinom olgularının klinikopatolojik özellikleri araştırılmıştır. Gereç ve Yöntem: Kolorektal rezeksiyon materyalleri 2002-2011 yılları arasında değerlendirilen ve odaksal olarak solid büyüme paternine sahip alanları bulunan 50 az diferansiye adenokarsinom olgusu, 2010 Dünya Sağlık Örgütü sınıflamasında tanımlanan kriterlere göre geriye dönük olarak yeniden değerlendirilmiş, evrelendirilmiş ve medüller karsinom olasılı- ğı açısından araştırılmıştır. Bulgular az diferansiye adenokarsinomlarda izlenen bulgular ile nonparametrik testlerle karşılaştırılmıştır. Bulgular: Yedi olgu medüller karsinom olarak değerlendirilmiş olup incelenen dö- nemde değerlendirilen 1128 olgu içerisindeki oranı %0,62’dir. Olguların üçü kadın, yaş ortalaması 62±5,9’dur (Dağılım:41-80). Tümörler sağ kolon yerleşimli (5/7) ve ekspansif büyüme paternine sahip olup (6/7), belirgin Crohn-benzeri lenfoid reaksiyon (5/7) ve tümörü infiltre eden lenfositler (7/7) göstermektedir. Az diferansiye adenokarsinom olarak sınıflanan 43 olgu ile karşılaştırıldığında lenfovasküler invazyon (%28’e karşılık %39,5), pT4 (%14,3’e karşılık %20,9) ve pN2 tümör oranının (%14,3’e karşılık %30,2) daha düşük olduğu; perinöral invazyon, tümör “tomurcuklanması” ve “kirli nekroz”un ise hiç olmadığı (p=0,002, ki-kare) dikkati çekmiştir. Sonuç: Medüller karsinomlar, sıklıkla sağ kolon yerleşimli, ekspansif büyüyen, göreceli olarak daha erken evrede izlenen ancak özel histolojik görünümleri ve ayırıcı tanı güçlükleri nedeniyle üzerinde durulması gereken tümörlerdir. Serimizde izlenen bulguların literatürle uyumlu olduğu görülmüştür. Çalışma, bu az görülen ancak Lynch sendromu ile ilişkisi gibi önemli klinik yansımaları olabilecek antiteye klinik duyarlılığın artırılması amacıyla sunulmuştur.

Anahtar Kelimeler:

Kolon kanseri, medüller karsinom, Lynch sendromu, histopatoloji

Histopathological approach to colorectal medullary carcinomas and their clinicopathological importance

Background and Aims: Medullary carcinomas are rare tumors, constituting less than 1% of all colorectal cancers, characterized with nongland-forming, solid sheets of malignant cells with vesicular nuclei, prominent nucleoli and abundant pink cytoplasm. They are important tumors due to their relationship with high microsatellite instability and Lynch syndrome. We reviewed the clinicopathological features of medullary carcinomas. Materials and Methods:The resection specimens of 50 poorly differentiated adenocarcinomas, examined between 2002-2011 and showing at least focal areas with a solid growth pattern, were retrospectively reviewed, re-classified, and re-staged according to the World Health Organization 2010 classification for features of medullary carcinoma. The clinicopathological findings were compared statistically with poorly differentiated adenocarcinomas using nonparametric tests.Results: Seven cases were reclassified as medullary carcinoma, constituting 0.62% of 1128 colorectal tumors diagnosed using their resection specimens within the given period. Three of the cases were female, and the mean age was 62± 5.9 years (range: 41-80 years). Tumors were located in right colon (5/7), showed expansive growth pattern (6/7), prominent Crohn's-like lymphoid reaction (5/7), and tumor-infiltrating lymphocytes (7/7). When compared with 43 poorly differentiated adenocarcinoma cases, the lower incidence of lymphovascular invasion (28% versus 39.5%), pT4 (14.3% versus 20.9%) and pN2 tumors (14.3% versus 30.2%) and absence of perineural invasion, tumor "budding" and "dirty necrosis" (p=0.002, chisquare) were noteworthy. Conclusions:Medullary carcinomas are rare tumors located predominantly in the right colon, showing an expansive growth pattern, and respectively, lower tumor and lymph node stages. They deserve special attention due to their special histological features and differential diagnostic pitfalls. The clinicopathological findings in our series are consistent with the previous literature. This study is presented to draw attention to this rare but important entity, which may have significant clinical implications in view of its relationship with Lynch syndrome.

Keywords:

Colon cancer, medullary carcinoma, Lynch syndrome, histopathology,

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Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System, 4th edition. IARC Press: Lyon 2010
Hamilton SR, Aaltonen LA. World Health Organization Classifica- tion of Tumours. Pathology & Genetics: Tumours of the Digestive System. Lyon: IARC Pres, 2000.
Greenson JK, Bonner JD, Ben-Yzhak O, et al. Phenotype of mic- rosatellite unstable colorectal carcinomas: Well-differentiated and focally mucinous tumors and the absence of dirty necrosis correlate with microsatellite instability. Am J Surg Pathol 2003; 27:563-70.
Zlobec I, Lugli A. Invasive front of colorectal cancer: dynamic in- terface of pro-/anti-tumor factors. World J Gastroenterol 2009; 15:5898-906.
Washington MK, Berlin J, Branton P, et al. Protocol for the exami- nation of specimens from patients with primary carcinoma of the colon and rectum. Arch Path Lab Med 2009; 133:1539-51.
Kevans D, Wang LM, Sheahan K, et al. Epithelial-mesenchymal transition (EMT) protein expression in a cohort of stage II colorectal cancer patients with characterized tumor budding and mismatch repair protein status. Int J Surg Pathol 2011;19:751-60.
Thirunavukarasu P, Sathaiah M, Singla S, et al. Medullary carcino- ma of the large intestine: a population based analysis Int J Oncol 2010;37:901-7.
Nguyen J, Coppola D, Shan Y, Zhang L. Poorly differentiated med- ullary carcinoma of the colon with an unusual phenotypic profile mimicking high grade large cell lymphoma - a unique case report and review of the literature. Int J Clin Exp Pathol 2014; 7:828-34.
Wick MR, Vitsky JL, Ritter JH, et al. Sporadic medullary carcinoma of the colon. A clinicopathologic comparison with nonhereditary poorly differentiated enteric-type adenocarcinoma and neuroendo- crine colorectal carcinoma. Am J Clin Pathol 2005; 123:56-65.
Karran P. Microsatellite instability and DNA mismatch repair in hu- man cancer. Semin Cancer Biol 1996;7:15-24.
Whitehall V, Leggett B. Microsatellite instability: detection and management in sporadic colorectal cancer. Gastroenterol Hepatol 2011; 26:1697-9.
Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syn- drome) proposed by the International Collaborative Group on HNPCC. Gastroenterology 1999; 116:1453-6.
Kim H, Jen J, Vogelstein B, Hamilton SR. Clinical and pathological charcateristics of sporadic colorectal carcinomas with DNA replica- tion errors in microsatellite sequences. Am J Pathol 1994; 145:148- 56.
Alexander J, Watanabe T, Wu TT et al. Histopathological identifi- cation of colon cancer with microsatellite instability. Am J Pathol 2001; 158:527-35.
Smyrk TC, Lynch HT, Watson PA, et al. Histologic features of he- reditary nonpolyposis colorectal carcinoma. In: Utsunomiya J, HT Lynch, eds. Hereditary colorectal cancer. Tokyo. Springer-Verlag 1990;357-62.
Joost P, Bendahl PO, Halvarsson B, et al. Efficient and reproducible identification of mismatch repair deficient coloncancer: validation of the MMR index and comparison with other predictive models. BMC Clin Pathol 2013; 13:33.
Umar A, Bolan CR, Terdiman JP, et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch Syndrom) and microsatellite instability. J Natl Cancer Inst 2004; 96:261-8.
Chapusot C, Martin L, Bouvier AM, et al. Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas. Br J Cancer 2002; 87:400-4.
Sinicrope FA. DNA mismatch repair and adjuvant chemotherapy in sporadic colon cancer. Nat Rev Clin Oncol 2010; 7:174-7.
Seydaoğlu G, Özer B, Arpacı N, et al. Trends in colorectal cancer by subsite, age, and gender over a 15-year period in Adana, Turkey: 1993-2008. Turk J Gastroenterol 2013; 24:521-31.