Lung
Neuroendocrine tumors
Atypical carcinoid


Topic Completed: 9 December 2020

Minor changes: 9 December 2020

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PubMed Search: Atypical carcinoid[TI] lung

Andréanne Gagné, M.D., M.Sc.
Philippe Joubert, M.D., Ph.D.
Page views in 2020: 7,276
Page views in 2021 to date: 724
Cite this page: Gagné A, Joubert P. Atypical carcinoid. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungtumoratypicalcarcinoid.html. Accessed January 18th, 2021.
Definition / general
Essential features
  • Atypical carcinoids are defined as neuroendocrine tumors with 2 - 10 mitoses per 2 mm² or foci of necrosis
    • Tumors with morphologic features of carcinoid and > 10 mitoses per 2 mm² have been reported and are the focus of active research
  • Histologic features include neuroendocrine differentiation, with neuroendocrine growth patterns, salt and pepper chromatin with an inconspicuous nucleolus and moderate to abundant cytoplasm
  • Differentiation from typical carcinoid is crucial as they have a poorer prognosis and are more likely to metastasize
Terminology
  • Not recommended: moderately differentiated lung neuroendocrine carcinoma, grade 2 neuroendocrine carcinomas
  • Well differentiated neuroendocrine tumors G1 to G3 nomenclature is not currently applied in pulmonary carcinoids (Mod Pathol 2018;31:1770)
ICD coding
  • ICD-O: 8249/3 - atypical carcinoid tumor
  • ICD-10: C7A.090 - malignant carcinoid tumor of the bronchus and lung
  • ICD-11: 2C25.4 & XH51K1 - carcinoid or other malignant neuroendocrine neoplasms of bronchus or lung and neuroendocrine tumor, grade 2
Epidemiology
Sites
Etiology
  • Unknown
  • Can arise in the context of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and tumorlets (Thorax 2007;62:248)
Clinical features
Diagnosis
  • Even if a diagnosis of carcinoid tumor can be made with confidence on a biopsy or cytology sample, the definitive diagnosis of atypical carcinoid can only be made on a surgical resection, unless necrosis or increased mitotic activity is seen (Ann Oncol 2015;26:1604)
Laboratory
Radiology description
Radiology images
Prognostic factors
Case reports
  • 25 year old woman with a postpneumonectomy-like syndrome due to a bronchial atypical carcinoid tumor (BMC Pulm Med 2019;19:44)
  • 30 year old woman with a subcutaneous metastasis of a lung atypical carcinoid tumor (Medicine (Baltimore) 2018;97:e9415)
  • 45 year old woman with an endobronchial atypical carcinoid tumor with postobstructive mycobacterial infection (BMC Pulm Med 2019;19:41)
  • 77 year old woman with a bronchial typical carcinoid lung tumor and diffuse idiopathic neuroendocrine cell hyperplasia in the distal lung (J Thorac Dis 2017;9:E774)
Treatment
Clinical images

Images hosted on other servers:

Bronchial occlusion

Endobronchial tumor

Tumor near trachea

Gross description
  • Can be similar to typical carcinoids, as they are well circumscribed and round / ovoid tumors but differ in certain points (Cancer 2008;113:5)
    • On average, atypical carcinoids are larger
    • Cut surface is white-gray or tan like typical carcinoids but can be less homogeneous with pink or yellow-brown or red areas
Gross images
Frozen section description
Frozen section images
Microscopic (histologic) description
  • Diagnostic criteria:
    • Neuroendocrine morphology with 2 - 10 mitoses per 2 mm² or presence of necrosis
      • Necrosis can be in large zones but is usually punctate
      • Mitotic rate should be counted in the area with the highest proliferation rate (hot spot)
      • If mitotic rate is near cutoffs, assessment should be made on three sets of 2 mm² and their mean should count as the final mitotic rate
    • Rare tumors with morphologic features of carcinoid and > 10 mitoses per 2 mm² have been reported (Virchows Arch 2017;471:713, Am J Surg Pathol 2017;41:263, Diagn Pathol 2019;14:104)
  • Neuroendocrine histologic patterns similar to typical carcinoids: organoid, trabecular, rosette formation, papillary, pseudoglandular, follicular
  • Tumor cells are as typical carcinoid: uniform with a polygonal shape, round to oval nuclei with salt and pepper chromatin and inconspicuous nucleoli, along with moderate to abundant eosinophilic cytoplasm
  • Stroma is fine and highly vascularized; hyalinization, cartilage or bone formation are possible
Microscopic (histologic) images

Contributed by Philippe Joubert, M.D., Ph.D.
Peripheral carcinoid

Peripheral carcinoid

Histologic pattern: rosettes

Histologic pattern: rosettes

Histologic pattern: organoid

Histologic pattern: organoid

Histologic pattern: papillary

Histologic pattern: papillary

Histologic pattern: solid

Histologic pattern: solid

Cytologic features: salt and pepper chromatin

Cytologic features: salt and pepper chromatin


Cytologic features: spindle cell features

Cytologic features: spindle cell features

Cytologic features: eosinophilic cytoplasm

Cytologic features: eosinophilic cytoplasm

 Increased mitotic rate Increased mitotic rate

Increased mitotic rate

Necrosis (larger focus) Necrosis (larger focus)

Necrosis (larger focus)


Necrosis (punctate)

Necrosis (punctate)

Lymphovascular invasion with punctate necrosis

Lymphovascular invasion with punctate necrosis

Stroma: ossification

Stroma: ossification

AE1/3

AE1 / AE3

CD56

CD56

Chromogranin

Chromogranin


TTF1

TTF1

Ki67

Ki67

Elevated proliferation rate

Elevated proliferation rate

Virtual slides

Images hosted on other servers:

Atypical lung tumor with focal necrosis

Cytology description
  • Cells and architecture similar to typical carcinoid tumors but can differ in several ways (Cibas: Cytology - Diagnostic Principles and Clinical Correlates, 4th edition, 2014)
    • Groups of cells tend to be looser, with more isolated cells; rosette structures might be seen
    • Population of tumor cells can be less uniform with slight pleomorphism
    • Focal necrosis can be seen
    • Mitoses can be seen but should be rare
    • Even though the diagnosis can be suggested, a thorough examination of the surgical resection remains necessary to classify the tumor
Cytology images
Positive stains
Negative stains
Molecular / cytogenetics description
  • Mutations in the chromatin remodeling genes, including MEN1 and SWI/SNF complex (Transl Lung Cancer Res 2017;6:513)
  • RB1 and TP53 are uncommon
  • Low number of chromosomal imbalances
Sample pathology report
  • Right lung, superior lobe, transbronchial biopsy:
    • Carcinoid tumor, not further classified (see comment)
    • Comment: The presence of focal necrosis or increased mitotic activity on this biopsy combined with the classic morphology of a carcinoid tumor favors a diagnosis of atypical carcinoid. However, the definitive diagnosis will be made on the resection specimen.
Differential diagnosis
Board review style question #1

    A patient undergoes a lobectomy for a well circumscribed nodule. On H&E slide, the tumor exhibits a well differentiated neuroendocrine morphology and you observe the histologic features presented in the image. Which of the following statements is true?

  1. A Ki67 proliferation rate of > 10% is diagnostic
  2. It is defined as a well differentiated neuroendocrine tumor with 2 - 10 mitoses per 2 mm² or foci of necrosis
  3. It is defined as a well differentiated neuroendocrine tumor with 2 - 10 mitoses in 1 high power field or foci of necrosis
  4. This diagnosis can be made with certainty on small samples (biopsies and cytology)
Board review style answer #1
B. It is defined as a well differentiated neuroendocrine tumor with 2 - 10 mitoses per 2 mm² or foci of necrosis. The picture shows a carcinoid lung tumor with a classical neuroendocrine morphology and 2 mitoses in 1 high power field. Even though the whole tumor is not presented here, the presence of 2 mitoses is sufficient for an atypical carcinoid diagnosis.

While Ki67 proliferation rate is frequently > 10% in atypical carcinoids, this feature is not part of the diagnosis (A). C is nearly exact but mitotic count is not made on 1 high power field. Finally, the diagnosis can be suggested on small samples but a thorough examination of a resection specimen is necessary to confirm an atypical carcinoid diagnosis (D).

Comment Here

Reference: Atypical carcinoid
Board review style question #2

    Regarding pulmonary atypical carcinoids, which of the following statements is true?

  1. Differentiating them from typical carcinoid is crucial as they have a poorer prognosis and are more likely to metastasize
  2. Neuroendocrine immunohistochemical markers (chromogranin, synaptophysin and CD56) are systematically positive
  3. They are less likely to be peripherally located than typical carcinoids
  4. They frequently harbor ALK-ELM4 fusions
Board review style answer #2
A. Differentiating them from typical carcinoid is crucial as they have a poorer prognosis and are more likely to metastasize. Neuroendocrine immunohistochemical markers are not always positive and can be completely negative in a small subset of atypical carcinoids (B). Regarding their location, atypical carcinoids are more frequently peripherally located and typical carcinoids are more frequently central (C). ALK-EML4 fusions are not found in atypical carcinoids (D).

Comment Here

Reference: Atypical carcinoid
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