Journal of Cytology
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Year : 2012  |  Volume : 29  |  Issue : 2  |  Page : 131-132
Skull metastasis as initial presentation in atypical pulmonary carcinoid

Department of Pathology, The Gujarat Cancer and Research Institute, Ahmedabad, India

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Date of Web Publication12-Jun-2012

How to cite this article:
Gupta A, Gupta M, Shah M, Patel T, Trivedi P, Shah M. Skull metastasis as initial presentation in atypical pulmonary carcinoid. J Cytol 2012;29:131-2

How to cite this URL:
Gupta A, Gupta M, Shah M, Patel T, Trivedi P, Shah M. Skull metastasis as initial presentation in atypical pulmonary carcinoid. J Cytol [serial online] 2012 [cited 2022 Jun 28];29:131-2. Available from:

Atypical carcinoid tumors constitute a very rare source of metastasis to skull and orbit and even rarer is their initial manifestation as bone metastasis. We share our experience of a rare morphological feature and an even rarer clinical presentation of an atypical pulmonary carcinoid. Role of MIB- 1 in differentiating the spectrum of neuroendocrine tumors (NET) is highlighted.

A 60-year-old male with a past history of smoking was referred to our hospital with complaints of left orbital proptosis, blurring of vision and diffuse swelling in left parietal region for past two months. Patient also complained of chest pain, breathlessness and cough for past 15 days. No history of diarrhea or flushing was present. Contrast enhanced computed tomography (CECT) of the brain revealed a lesion involving left temporal bone with enhancing intra-cranial, extra-cranial and intra-orbital soft-tissue component. Fine needle aspiration cytology (FNAC) from the lesion was done using 22 gauge needles. Smears were prepared on glass slide, fixed in 100% methanol and stained with Papanicolaou stain. FNAC revealed cellular smears composed of small round cells lying discretely as well as in loose aggregates in a clean background. Cells displayed mild pleomorphism, had salt and pepper chromatin, inconspicuous nucleoli and moderate amount of pale eosinophilic cytoplasm. Mitoses were present. An interesting and prominent finding was the presence of variable sized intranuclear inclusions. Few of the inclusions were large enough to impart an appearance of signet ring cells [Figure 1]. A differential diagnosis of metastatic low-grade carcinoma or metastatic neuroendocrine carcinoma was offered. To search the source of secondary tumor, CECT scan of thorax was done which revealed left-sided small endobronchial lesion with distal collapse, mediastinal nodal mass and liver metastasis. Image guided biopsy from the lesions in lung and liver was done which revealed an atypical carcinoid tumor. Immunohistochemical stains revealed strong positivity for synaptophysin, chromogranin, epithelial membrane antigen and thyroid transcription factor-1 (TTF- 1). MIB-1 labeling index was low (5%) [Figure 2]. Positivity for neuroendocrine markers and TTF-1 proved a well differentiated NET of pulmonary origin.
Figure 1: (a) Tumor cells showing mitoses (Pap stain, ×400) (b) Tumor cells showing intranuclear inclusions (Pap stain, ×400) (c) Inset shows intranuclear inclusions (Pap stain, ×1000)

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Figure 2: Photomicrograph showing (a) strong positive immunohistochemical staining TTF-1 (IHC, ×100) and (b) low MIB-1 LI (IHC, ×400)

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Differential diagnosis included metastatic low grade adenocarcinoma. FNAC of the skull lesion displayed a neuroendocrine morphology (discretely lying cells with loose aggregates, salt and pepper chromatin) but the predominance of intranuclear inclusions led to confusion. Some inclusions were so large so as to give an impression of signet ring cell. This is a rare finding in NET and has been described infrequently in the literature.[1] The diagnostic difficulty was further confounded by the unusual clinical presentation. Cytological features described in our case apart from the intranuclear inclusions are similar to those described in literature.[2] TTF-1 is expressed in well-differentiated pulmonary NETs including atypical carcinoids. This is an important marker in differentiating them from extrapulmonary well differentiated NETs as the latter rarely express it.[3] According to several studies, MIB-1 LI is an important ancillary tool in differentiating the spectrum of NETs particularly in small biopsy specimens. MIB-1 LI is less than 2% in typical carcinoid (TC), less than 20% in atypical carcinoid (AC) and is significantly higher than 20% in small cell lung carcinoma and large cell neuroendocrine carcinoma.[4] In our case total excision of the pulmonary mass was not done as the patient had wide spread metastases. A single mitosis was identified in the biopsy and frequent mitoses were identified in the cytology smears. As the MIB-1 LI was low (5%) and in presence of other supportive histological and immunohistochemical features, the diagnosis of AC was established.

In a large study, 11 out of 90 patients (1.2%) of metastasized carcinoid tumor had a symptomatic bone metastasis predominantly located in axial skeleton. The interval between diagnosis of a carcinoid tumor and the appearance of bone metastasis showed a wide range and only two patients had bone metastasis at the time of diagnosis of carcinoid tumor. [5] Only a single case of a 19-year-old man presenting with skull metastasis as an initial manifestation in an atypical pulmonary carcinoid has been described in the literature.[6]

In conclusion, we share our experience of a rare morphological feature (intranuclear inclusions) and an even rarer clinical presentation of an atypical pulmonary carcinoid. Role of MIB-1 in differentiating the spectrum of NET is highlighted. Presence of intranuclear inclusions can be misleading. Merely the presence of intranuclear inclusions in presence of other supportive cytological features like loose aggregates along with singly lying cells, salt and pepper chromatin should not alter the correct diagnosis.

   References Top

1.Crapanzano JP. Cytology of low-grade endocrine neoplasm involving liver: a series of 24 specimens, including 4 with hepatoid or glandular features. Diagn Cytopathol 2004;30:31-8.  Back to cited text no. 1
2.Nicholson SA, Ryan MR. A review of cytologic findings in neuroendocrine carcinomas including carcinoid tumors with histologic correlation. Cancer 2000;90:148-61.  Back to cited text no. 2
3.Agoff SN, Lamps LW, Philip AT, Amin MB, Schmidt RA, True LD, et al. Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine tumors. Mod Pathol 2000;13:238-42.  Back to cited text no. 3
4.Rekhtman N. Neuroendocrine tumors of the lung: an update. Arch Pathol Lab Med 2010;134:1628-38.  Back to cited text no. 4
5.Meijer WG, van der Veer E, Jager PL, van der Jagt EJ, Piers BA, Kema IP, et al. Bone metastases in carcinoid tumors: clinical features, imaging characteristics, and markers of bone metabolism. J Nucl Med 2003;44:184-91.  Back to cited text no. 5
6.Isaka T, Maruno M, Suzuki T, Sato M, Yoshimine T. Skull metastases from atypical pulmonary carcinoid tumor in a 19-year-old man. Neurol Med Chir (Tokyo) 2006;46:609-13  Back to cited text no. 6

Correspondence Address:
Anuja Gupta
Junior Lecturer, Department of Pathology, GCRI, Ahmedabad
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9371.97156

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