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Background
These are rare neoplasms occurring in an obscure gland. They account for 2-4% of all mediastinal tumors. The early pathology literature referred to many of these tumors as thymic carcinoid tumors. However, unlike carcinoid tumors occurring in other organs such as the lung, these tumors were clinically malignant in the vast majority of cases. Thus investigators classify these tumors as part of the spectrum of neuroendocrine carcinomas. Well differentiated tumors may show prominent spindling, mucinous stroma, oncocytic changes, and divergent cell lines with mesenchymal elements and amyloid-like stroma. High grade tumors may show areas indistinguishable from small cell carcinoma.
Tumors with oncocytic features must be distinguished from other simulators including paragangliioma, parathyroid adenomas, and metastastic tumors with oncocytic changes (such as breast CA, renal cell CA, malignant mesothelioma, and metastatic melanoma).
OUTLINE
HISTOLOGICAL TYPES CHARACTERIZATION General Pathol Case Rev 2001;6:41-48 Mild cellular atypia
<3 MF/10 hpf
Small foci of comedonecrosisModerate cellular atypia
4-9 MF/10 hpf
More extensive foci of necrosisSevere or prominent cellular atypia
>10 MF/10 hpf
Extensive areas of necrosisMajority of tumors have prominent nesting or zellballen pattern
Common to have large balls with artifactual clefting
Necrotic centers with comedolike areas and calcifications
Monotonous small microacinar structures resembling rosettes
Solid pattern
Ribbon-like growthVascular and lymphatic invasion common in higher-grade lesions VARIANTS CYSTIC
Two cases of primary neuroendocrine carcinoma (carcinoid tumor) arising in the walls of a multilocular thymic cyst (MTC) are described. The patients were 2 men, ages 36 and 44 years. Clinically, the patients had chest pain, cough, and dyspnea. Radiographic evaluation demonstrated the presence of anterior mediastinal tumor in both patients, and complete surgical resection of the tumor mass was performed.
The tumors measured approximately 6 and 8 cm in greatest dimension and were cystic with solid areas but did not show areas of necrosis or hemorrhage.
Histologic examination revealed a cystic tumor with features similar to those previously described for MTCs. In addition, in the walls of the cystic structures, there was cellular proliferation arranged in a nesting growth pattern, similar to the more solid areas of the tumor. The tumor was characterized by a homogenous cellular proliferation with mild cellular atypia and no more than 2 mitotic figures per 10 high-power fields.
Immunohistochemically, the tumor cells showed strong positive reactions for keratin and neuroendocrine markers, ie, chromogranin and synaptophysin. Both patients were alive after periods of 12 and 18 months.Am J Surg Pathol 1995;19:1277-1285 Respiration 1993;60:247-249
SPECIAL STAINS/
IMMUNO-PEROXIDASECHARACTERIZATION Special stains Immunoperoxidase CAM 5.2+
Synaptophysin + 73% of cases
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS Am J Clin Pathol 2000;114:100-110
Linked to degree of differentiation
Clinicopathologic and DNA Cytometric Analysis of Carcinoid Tumors of the Thymus
Koichi Goto, M.D., Tetsuro Kodama, M.D., Yoshihiro Matsuno, M.D., Tomoyuki Yokose, M.D., Hisao Asamura, M.D., Noriki Kamiya, M.D. and Yukio Shimosato, M.D.
Pathology Division (KGTY, NK), National Cancer Center Research Institute East, Kashiwa, Chiba; Division of Thoracic Oncology (KG), National Cancer Center Hospital East, Kashiwa, Chiba; Division of Medical Oncology (TK), Clinical Laboratory Division (YM), and Division of Thoracic Surgery (HA), National Cancer Center Hospital, Tsukiji, Tokyo; and Department of Pathology (YS), Keio University School of Medicine, Shinanomachi, Tokyo, Japan
Mod Pathol 2001;14:985-994 Abstract quote
Twelve cases of carcinoid tumors of the thymus were reviewed in terms of clinicopathologic, histochemical, and immunohistochemical features and DNA ploidy patterns.
The collective consisted of nine male and three female patients, aged 34 to 74 years, of whom five (42%) had symptoms. Eleven patients underwent surgical resection, and one with systemic metastases was autopsied. In the 11 resected patients, tumors had invaded surrounding structures in four cases, and mediastinal lymph node metastases were detected in six. Recurrence occurred in two of the resected patients (18%), and the 5-year survival rate was 82%.
Histologically, all tumors showed an organoid growth pattern with delicate fibrovascular stroma. In addition, three tumors had unusual morphologic features such as combined features of carcinoid tumor and thymoma and solid growth pattern with occasional large tumor cells. Mitotic counts ranged from 1 to 14 per 10 high-power fields with a mean count of 4.9. Central necrosis within solid nests was observed in nine tumors. Classification of this series using the WHO histologic classification system resulted in categorization of all 12 tumors as atypical carcinoids. All tumors were positive for Grimelius staining and for cytokeratin. Immunohistochemical staining documented the presence of moderately to strongly positive neuroendocrine markers such as neuron-specific enolase, chromogranin A, synaptophysin, and neural cell adhesion molecule. No correlation between proliferative activity based on the Ki67 labeling index and prognosis or lymph node metastasis was found. Concerning DNA ploidy patterns, only one tumor with multiple lymph node metastases was considered to be aneuploid.
In conclusion, although all of our cases were histologically classified as atypical carcinoid tumors of the thymus, most were diploid, and the patients enjoyed a relatively good prognosis.
Thymic neuroendocrine carcinoma: a clinicopathologic study in four patients.Sugiura H, Morikawa T, Itoh K, Ono K, Okushiba S, Kondo S, Katoh H.
Second Department of Surgery, Hokkaido University Hospital, N-14, W-5, Sapporo 060-8648, Japan.
Ann Thorac Cardiovasc Surg 2000 Oct;6(5):304-8 Abstract quote BACKGROUND: Thymic neuroendocrine carcinoma (carcinoid) is rare. Here we present four cases of this unusual neoplasm to provide more clinical, radiologic, and prognostic data.
MATERIALS AND METHODS: Four male patients with an average age of 44 years (range 27-63) were identified as having thymic neuroendocrine carcinoma and were reviewed retrospectively.
RESULTS: One patient had Cushing's syndrome with elevated serum ACTH. Three others were asymptomatic with normal laboratory findings, one case was associated with MEN type 1. All underwent complete resection along with invaded adjacent structures. Local recurrence developed in two patients at 45 and 98 months after the initial excision. Both patients died at 90 and 105 months, respectively. The other two patients are alive and have been disease-free for 27 and 120 months, respectively.
CONCLUSIONS: Thymic neuroendocrine carcinomas have a rather poor prognosis based on their tendency to recur and metastasize many years after the initial operation. Therefore, prolonged follow-up is essential for these tumors.
p53
p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors.
Gal AA, Sheppard MN, Nolen JD, Cohen C.
1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Mod Pathol. 2004 Jan;17(1):33-9 Abstract quote.
Thymic neuroendocrine tumors are biologically aggressive neoplasms with extensive local invasion and high mortality. Although various markers of cellular proliferation and apoptosis have correlated with degrees of tumor differentiation in pulmonary neuroendocrine neoplasms, they have not been systematically studied in thymic neuroendocrine tumors.
We immunostained 21 cases of thymic neuroendocrine tumors for p53, MIB-1, and the apoptosis-related markers Bcl-2, Bcl-x, and Bax. By histological classification the cases were low-grade (nine cases), intermediate-grade (eight cases), and high-grade (four cases) thymic neuroendocrine tumors. p53 was expressed in five cases: 1/9 low grade, 3/8 intermediate grade, and 2/4 high grade. The mean cellular proliferation (MIB-1) was 7.1% (range 2-12%) in low-grade thymic neuroendocrine tumors, 6.1% (range 2-15%) in intermediate-grade thymic neuroendocrine tumors, and 34.2% (range 2-80%) in high-grade thymic neuroendocrine tumors. Bcl-2 was expressed in 16 cases: 7/9 low grade, 5/8 intermediate grade, and 4/4 high grade. Bcl-x was expressed in 16 cases: 7/9 low grade, 6/8 intermediate grade, and 3/4 high grade. Bax was expressed in 13 cases: 5/9 low grade, 4/8 intermediate grade, and 4/4 high grade. The presence of mutant p53 in the tumor was associated with a statistically significant decreased mean survival (P<0.05). In contrast, either by positive or negative staining or by the score technique (staining intensity x percentage of cells staining), the presence of Bcl-x was associated with an increased mean survival (P<0.05). Finally, a Bcl-x : Bax ratio >/=1 was also associated with an increased mean survival, as compared to a Bcl-x : Bax ratio >/=1 (P<0.05).
Our study shows that p53 expression and certain apoptosis markers correlate with survival. The expression of these markers may account for differences in biological behavior.Survival-5YRS 50% 20% 0% Mod Pathol 2000;13:489-494.
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