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Dr. Akanksha Kushwah, 1st year resident Pathology
1 PAP stained slide FNA from a lung mass
21 year female.
Smears are cellular and show tumor cells in loose clusters. These tumor cells are mildly pleomorphic. They have scant to moderate amount of cytoplasm, round nuclei with granular chromatin and inconspicuous nucleoli. Few of these cells show irregular nuclear rim and small nucleoli. Background show alveolar mecrophages along with some neutrophils. Necrosis and mitosis are not noted.
DIAGNOSIS Typical carcinoid tumor .
DISCUSSION Carcinoid tumor .
lack of malignant potential or particularly benign features) .History 1888 – First described by Labarsch 1907 – Oberndorfer coined term ―Karzinoide‖ (carcinoma-like.
The term enterochromaffin refers to the ability to stain with potassium chromate (chromaffin). .CARCINOID TUMOR Carcinoid tumors were so named because they seemed morphologically different and clinically less aggressive than the more common intestinal adenocarcinoma. Carcinoids arise from enterochromaffin cells of the gastrointestinal tract. a feature of cells that contain serotonin.
GI tract.000 for men and women. respectively. ovaries .47 and 2.000 Black M/F Occurrence rate 1:300 autopsies Reported in a number of organs Lungs.Carcinoid Tumor 5th to 7th decade of life Incidence 2. 4.98/100.48 and 3. bronchi.58 per 100.
5-HT. 5-HIAA.Secretory products of carcinoid Amines 5HT 5-HIAA 5-HTP Histamine Tachykinins Kallikrein Substance P (32%) Peptides Other Pancreatic polypeptide (40%) Prostaglandins Chromogranins (100%) Neuropeptide K (67%) Neurotensin (19%) HCGα (28%) HCGβ Motilin Dopamine HCG. 5-HTP. Human chorionic gonadotropin. 5-Hydroxyinoleacetic acid. 5-Hydroxytryptamine. 5-Hydroxytryptophan .
asymptomatic. appendix. GU tract) 1/3 of midgut tumors symptomatic 10% associated with carcinoid syndrome Hindgut rarely cause carcinoid. even when metastatic . prox colon) Hindgut (distal colon. Classified by embryologic origin Foregut (respiratory tract. rectum. stomach) Midgut (small intestine. thymus.
multiple polypeptides Solid mass of cells Argentaffin Serotonin. ileum. duodenum. sigmoid. appendix. serotonin. polypeptides Mixed Variable None Metastasis to liver Stomach 20-25% Small intestine 35% Rectum <10% of tumors >2cm Asc colon 60% Appendix 2% Classical Rare Carcinoid syndrome Atypical . rectum Histology Silver Staining Secretory products Trabecular Argyrophil 5-HT. prostaglandins. histamine. pancreas. ascending colon Hindgut Transverse and descending colon. bronchus Midgut Jejunum.Characteristics of carcinoids Foregut Localization Stomach.
trabecular. Arise from Kulchitsky cell. . rosette-like arrangements) that suggest neuroendocrine differentiation. and nuclei with a finely granular chromatin pattern. insular. Tumour cells have uniform cytologic features with moderate eosinophilic.LUNG Carcinoid tumours are characterized by growth patterns (organoid. ribbon. palisading. finely granular cytoplasm.
CLASSIFICATION Typical – Well-differentiated. – Fewer than 2 mitosis/10 hpf – Lack necrosis Atypical or anaplastic – Increased nuclear atypia. containing small regular cells with rounded nuclei. – Mitotic activity 2-10/ 10 hpf – Areas of necrosis .
Atypical carcinoid is more commonly peripheral.LOCALIZATION Typical carcinoid is uniformly distributed throughout the lungs. .
associated with MEN1. which can produce a number of paraneoplastic syndromes including Cushing's syndrome. . hemoptysis or chest pain The tumors are capable of secreting several different hormones. which occurs in less than 5% of patients Rarely. acromegaly.Clinical Presentation Patients usually present in their 50s with recurrent pneumonia. and the carcinoid syndrome. cough.
Uniform small cells. FNA samples. papillary and oncocytic tumours and spindle cell forms . some paslisades or trabeculae. Bare nuclei are common but necrosis is rare. Variants include clear cell tumours. stippled chromatin.CYTOLOGY Best seen in brushings and FNA samples.plexiform vascular fragments. rounded nuclei. Marked cell dissociation.
.Loose aggregates of slightly irregular small sized tumor cells. Delicate. capillaries with loosely attached radiating tumor cells. Round or oval nuclei with a irregular ‗salt and pepper‘ chromatin pattern.
Carcinoid tumour. Dispersed population of regular small neuroendocrine cells. Background of plexiform capillaries (PAP) .
Cells are small and polygonal . cords. or broad sheets.Cells tend to group in nests.
histological section H&E). H&E. B. . spindle cell type. MGG.Spindle cell carcinoid Imprint from resected lung specimen: carcinoid tumour. Unusually elongated cells with a mesenchymal appearance (A. C.
yellow-tan on cut surface Grow slowly Overlying mucosa may be intact or ulcerated. .MACROSCOPY Grossly. small. firm submucosal nodules.
Central bronchial carcinoid tumour .
More peripherally located carcinoid tumour with bronchiectasis .
Typical carcinoid presenting as round, partially endobronchial mass. Note the post-stenotic pneumonia
Carcinoid tumours are classically composed of uniform polygonal cells with
finely granular chromatin,
inconspicuous nucleoli and
scant to moderate amounts of eosinophilic cytoplasm
A variety of growth patterns are encountered frequently within one tumour. The most common patterns are the organoid and trabecular, in which the tumour cells are respectively arranged in nests or cords. Other patterns include spindle cell, papillary, pseudoglandular, rosette formation and follicular.
but in some tumours the stroma is hyalinized. In rare cases there are also multiple tumourlets or multiple carcinoid tumours. There is generally a highly vascularized fibrovascular stroma. or it shows cartilage or bone formation. .
with a fine vascular stroma.Tumour cells grow in an organoid nesting arrangement. The moderate amount of cytoplasm is eosinophilic and the nuclear chromatin finely granular. .
Trabecular pattern. .
Oncocytic features with abundant eosinophilic cytoplasm. .
. A Small necrotic focus.Atypical carcinoid.
The tumour cells show carcinoid morphology with moderate eosinophilic cytoplasm and finely granular nuclear chromatin.ATYPICAL CARCINOID: single mitosis is present in this high power field. .
. Carcinoids show TTF-1 staining.IMMUNOHISTOCHEMISTRY Most carcinoid tumors stain for cytokeratin but up to 20% may be keratin negative Neuroendocrine markers such as chromogranin. particularly in TC CD99. synaptophysin. quite variabily. Leu-7 (CD57) and N-CAM (CD56) are typically strongly positive. is also positive in many carcinoids Ki 67 is more often positive in AC than TC and is related to survival.
. Strong cytoplasmic chromogranin staining.Typical carcinoid.
The tumour cells show strong membranous staining for CD56 .
.PROGNOSIS The overall 5.and 10-year survival rates are worse for AC (61-73% and 35-59%) than TC (90-98% and 82-95%) Further histopathological prognostic criteria (beyond necrosis and mitoses) include vascular invasion and nuclear pleomorphism.
Gastrointestinal Carcinoid Most common site (Sabiston) 1. Appendix (45%)** 2. Small intestine (28%) (last 2ft of ileum) 3. Rectum (16%) (Cheek RC et al) According to SEER database of 11.427 carcinoids 1973-1997 Small intestine (45%)** Rectum (20%) Appendix (16%) Colon (11%) Similar results database study from a Swedish registy 5.184 carcinoid tumors 1958-1998 .
They arise from endocrine cells in the lamina propria and submucosa. And are detected most commonly in the patients in their 40s or 50s.Appendix Carcinoid tumors are the most common neoplasms in the appendix. . Approximately 1 in 300 appendixes contain a carcinoid tumor.
at the base of the appendix (10%) and metastatic disease – Obstruction. or carcinoid syndrome with tumor mets to liver 5-yr survival overall 71%. located distal 1/3 of appendix Symptomatic case tend to have larger tumor. F>M Majority asymptomatic. appendicitis. 10 to 30% with distant metastasis .
Appendix: Surgery Depends on the site of primary tumor Appendix Prognosis best predicted by size <1cm – Simple appendectomy adequate >2cm – right hemicolectomy 1 to 2 cm decide by location Base of appendix or invading mesentery Right hemicolectomy Appendectomy alone if tumor can be fully resected Tumor size <1cm Metastasis 2% 1-2cm >2cm 50% 80% Mesoappendiceal invasion regardless of tumor size – Right hemicolectomy Studies show that recurrence unlikely with small tumors with this feature treated by appendectomy alone. (Kulke. N Engl J Med 1999) .
present with abdominal pain or SBO Carcinoid syndrome in 5 to 7% of patients Multiple tumors in up to 30% 5-yr survival 36% with distant metastasis .Small Intestine ~1/3 of small intestine neoplasms Commonly within 60cm of ileocecal valve 6th and 7th decade.
Small intestine Often metastasis to lymph nodes or liver Treatment Resection of involved segment and mesentery Even in known metastasis .
Carcinoid of ileum .
at diagnosis. average tumor size – 5cm 2/3 patients had local nodal or distant metastasis . anorexia. or weight loss Carcinoid syndrome uncommon Majority in right colon Cecum Asymptomatic until tumor becomes large In 2 studies.Colon 7th decade Presenting with abdominal pain.
76% Regional .Colon 5-yr survival based on metastasis Local .30% Small localized tumors likely cured by resection .72% Distant .
Rectum 6th decade Size Majority found incidentally on rectal exam or endoscopy Uncommon presentation includes rectal bleeding or pain Carcinoid syndrome rare Size correlates with metastasis Often to lymph nodes or liver Metast asis 1cm 11.9cm >2cm Rare ~10% >70% .
5-yr survival rates Localized (90%) Regional (49%) Distant metastasis (26%) SEER database .
e.Stomach Three Categories Type 1 70 to 80% of gastric carcinoids Associated with chronic atrophic gastritis and often pernicious anemia Derived from enterochromaffin-like (ECL) cells Hypothesized that ECL cells develop into carcinoid after chronic stimulation by high gastric levels i. pts with atrophic gastritis .
Gastric Carcinoids .
Type 1 6th and 7th decade. F>M Carcinoid syndrome rare Usually indolent and generally benign condition Metastases <10% of tumors <2cm ~20% present in larger tumors .
) Behave similar to type 1 .Type 2 Associated with gastrinomas (ZollingerEllison syndrome) or MEN type 1 <5% of gastric carcinoids ECL cells MEN1 gene locus (11q13) appears to be involved in the pathogenesis of many of these tumors (Debelenko et al.
often produce serotonin .Type 3 ―sporadic carcinoids‖ – not associated with any other disease process 20% of gastric carcinoids Most aggressive – local or hepatic metastases up to 65% of patients May be associated with carcinoid syndrome o Often produce 5Hydroxytryptophan in contrast to type 1 and 2.
or autopsy [80%] When present—correlate with location and extent of tumor Carcinoid Syndrome .Clinical Manifestations Majority are asymptomatic and found incidentally at time of surgery. endoscopy.
and release a variety of polypeptides. store.Carcinoid Syndrome This is the term applied to a constellation of symptoms mediated by various humoral factors elaborated by some carcinoid tumors. and prostaglandins . biogenic amines. These tumors synthesize.
Tryptophan metabolism In normal subjects. however. Serotonin is then metabolized to 5hydroxyindoleacetic acid (HIAA) . this value may increase to 70 percent or more in patients with the carcinoid syndrome . one percent of dietary tryptophan is converted to serotonin.
esp. small bowel Other locations described >90% with carcinoid syndrome have metastatic disease.Malignant Carcinoid Syndrome Occurs in <10% patients with carcinoid tumors. Commonly tumors of GI tract. exceptions are bronchial and ovarian tumors Patients with the syndrome almost invariably have hepatic metastases .
Carcinoids do not produce the malignant carcinoid syndrome until they are no longer confined to the small bowel or mesentery. carcinoids can metastasize to the lungs. or almost any organ . bone. which. After spreading to the liver. perhaps because of the liver breakdown of tumor products. skin. in physiologic conditions. is taken up and stored in the platelets while the excesses are inactivated in the liver and lung and transformed into 5hydroxyindoleacetic acid (5-HIAA). Most of these tumors produce 5hydroxytryptamine.
Liver metastases .
Diarrhea – Secretory diarrhea occurs in 80 percent of patients and is often the most debilitating component of the syndrome. .CLINICAL FEATURES Cutaneous flushing – Episodic flushing is the clinical hallmark of the carcinoid syndrome. and occurs in 85 percent of patients.
CLINICAL FEATURES Bronchospasm – Ten to twenty percent of patients with the carcinoid syndrome have wheezing and dyspnea. often during flushing episodes Cardiac valvular lesions – Pathognomonic plaquelike deposits of fibrous tissue develop in the heart in approximately 3 to 4 percent of all patients with carcinoid tumors .
Prognosis Dependent on size. location of primary tumor Midgut tumors better survival than foregut and hindgut Resection of a carcinoid tumor localized to its primary site approaches a 100% survival rate 5-yr survival ~65 to 67% with regional disease 25 to 35% with distant metastasis Long-term palliation often can be obtain due to slow growing nature Chromogranin A found to be an independent predictor of an adverse prognosis .
often incidental finding Initial diagnostic test 24-hr urinary 5-HIAA Treatment and prognosis dependent on size and location of primary tumor Resection of tumor increases overall survival Metastases correlate with location and size of tumor .Summary >80% asymptomatic.
7 cm diameter in the inferior lobe of the left lung.Overdiagnosis of a typical carcinoid tumor as an adenocarcinoma of the lung: a case report and review of the literature. the diagnosis was changed to adenocarcinoma of the lung. After several immunohistochemical stainings. The first histological diagnosis was a metastasis of prostate cancer with lymphangiosis carcinomatosa. In 2010 a 77 year-old male patient was shown to have a tumor mass of about 1. .
The diagnosis was ultimately changed to typical carcinoid tumor without any signs of lymphatic vessel invasion. Further immunohistochemical studies were performed. CONCLUSION: The use of several immunohistochemical markers. careful evaluation of hematoxylin-eosin sections and the Ki-67 labelling index are important tools in discriminating between carcinoids and other bronchopulmonary carcinomas. .
D) Cytoplasmatic expression of chromogranin A. B) Cytoplasmatic expression of CK7. C) Nuclear expression of TTF1.A) HE-staining. B-G) Immunohistochemical stainings. . F) Plasma membrane associated expression of CD56. E) Cytoplasmatic expression of synaptophysin. G) Ki-67 labelling index of approximately 5%.
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