A 75-year-old male presented with 2 month history of right facial pain and jaw mass along the right angle of the mandible. Imaging studies showed a large, aggressive right superior nasal cavity mass with intracranial and orbital extension, measuring 7.9 x 6.6 x 3.0 cm. There was extensive enlargement of the right cervical lymph nodes and multiple bone lesions concerning for metastasis as well. Image-guided fine needle aspiration of the right cervical lymph node, level 2b, was successfully performed.

 

Authors

• Yodsuí Figueroa Hernández, MD. Cytopathology Fellow. Department of Pathology and Cell Biology. Columbia University Irving Medical Center. New York Presbyterian Hospital, New York, NY.
  
  
• Arash Lahoutiharahdashti, MD. Associate Professor of Pathology and Cell Biology. Department of Pathology and Cell Biology. Columbia University Irving Medical Center. New York Presbyterian Hospital, New York, NY.

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Figure 1	Figure 2	Figure 3
Figure 4	Figure 5	Figure 6

Images 1-6:

• Figure 1: FNA material, smear, Diff-Quik stain, 40x magnification
• Figure 2: FNA material, smear, Diff-Quik stain, 40x magnification
• Figure 3: Cell block, H&E stain, 40x magnification
• Figure 4: Cell block, INSM1 immunohistochemical stain, 40x magnification
• Figure 5: Cell block, synaptophysin immunohistochemical stain, 40x magnification
• Figure 6: Cell block, SSTR2A immunohistochemical stain, 60x magnification

Questions:

1. Based on the cytomorphology, architecture, and clinical information, what is the most likely diagnosis for this patient?
   
   
   1. High grade lymphoma
   2. Olfactory neuroblastoma
   3. Small cell carcinoma
   4. Metastatic Ewing sarcoma
   5. Merkel cell carcinoma
      
      
2. When evaluating a cytology smear from this tumor, which of the following best describes the characteristic cytologic findings?
   
   
   1. Stripped nuclei, single cells with high N:C ratios, Homer Wright rosettes with fibrillary cytoplasm and central neuropil, finely granular chromatin, and inconspicuous nucleoli.
   2. Uniform small round cells with fine chromatin, scant cytoplasm, and occasional nucleoli
   3. Oval to elongated hyperchromatic nuclei, with nuclear molding, necrosis and apoptosis
   4. Small to medium sized cells with round/oval nuclei, stippled chromatin, inconspicuous nucleoli, and scant cytoplasm
   5. Mixture of small to large cells with angulated nuclei, and scattered large cells with vesicular chromatin and prominent nucleoli
      
      
3. Which of the following immunohistochemical panels is most helpful in supporting the diagnosis?
   
   
   1. CD5, CD10, CD19, CD20, CD15, CD30
   2. GATA-3, TRPS-1, GCDFP-15, ALK, ER, PR
   3. Synaptophysin, chromogranin, INSM1, S100, Ki-67, SSTR2
   4. Desmin, Vimentin, MDM2, p16, Rb, E-cadherin
   5. CK20, Synaptophysin, Chromogranin, Cam5.2, NSE, MCPyV (nuclear)
      
      
4. Which anatomical site does this tumor originate from?
   
   
   1. Skin
   2. Lymph node/soft tissue
   3. Bone
   4. Cribriform plate of nasal cavity
   5. Retroperitoneum

Answers:

Question 1: Correct answer is B

Cytologic preparations show a highly cellular specimen composed of intermediate sized cells with scant cytoplasm and chromatin smearing. In image 1, in the 12 o’clock position, a glassy and opaque paranuclear blue body can be seen. Vaguely rosetting architectural arrangements can be appreciated on both smears. The main differential diagnoses for olfactory neuroblastoma, based on the cytomorphology, are other “small round blue cell” tumors, including small cell carcinoma, Merkel cell carcinoma, Ewing sarcoma, and small cell forms of non-Hodkin lymphoma. Without the presence of both rosetting, which by itself is non-specific, and fibrillar neuropil, which may be extremely hard to find in cytologic preparations, it is impossible to discern olfactory neuroblastoma from other entities within the differential diagnosis without the aid of immunohistochemical stains. Additionally helpful is consideration of the anatomic distribution of disease and the clinical context, both of which vary widely for entities within the above-listed differential diagnosis. Olfactory neuroblastoma is generally anatomically confined to the cribriform plate and upper nasal vault of patients of any age.

Question 2: Correct answer is A

Stripped nuclei, single cells with high N:C ratios, Homer Wright rosettes with fibrillary cytoplasm and central neuropil, finely granular chromatin, and inconspicuous nucleoli are the typical cytomorphologic findings in olfactory neuroblastoma. Cytology smears typically show hypercellularity, single forms and cell clusters, stripped nuclei, a variable number of Homer Wright rosettes with fibrillary cytoplasm. The nuclei are round with smooth nuclear membranes, finely granular chromatin, and inconspicuous nucleoli. Additionally, paranuclear “blue bodies” might be seen.
 
Question 3: Correct answer is C

Synaptophysin, chromogranin, INSM1, S100, Ki-67, and SSTR2 is the most helpful panel. The immunohistochemical profile of olfactory neuroblastoma generally shows diffuse staining for neuroendocrine markers. One third of olfactory neuroblastomas may react focally for pancytokeratin. Proliferation index, Ki-67, is variable and associated with tumor grade. Desmin or myogenin reactivity is seen in olfactory neuroblastoma with rhabdomyoblastic differentiation. Somatostatin receptor 2 (SSTR2) is expressed in olfactory neuroblastoma. SSTR2 is a G-protein coupled membrane receptor expressed in a variety of neural and neurosecretory tissue types. The dominant isoform in humans is SSTR2A. SSTR2 expression has been identified in a variety of endocrine-type tumors and is a favorable prognostic marker suggesting a role for somatostatin analogue–based imaging and therapy in this disease.

Question 4: Correct answer is D

Olfactory neuroblastomas originate from and are generally centered around the cribriform plate of the nasal cavity. The anatomical distribution of olfactory neuroblastoma is confined to the cribriform plate, superior turbinate (concha), and superior half of the nasal septum. Ectopic tumors within the paranasal sinuses (excluding the ethmoid) are rare, except in recurrent tumors.

References:

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