October 2018 Case of the Month - Further Information

Submitted by Dr Alice Westwood

Clinical History:  A 77-year-old male presented with left facial nerve palsy and a history of a painless left parotid lump for 18 months and a recent increase in size. He had no systemic symptoms and no relevant past medical history. Ultrasound of the left parotid revealed a 2 x 3cm irregular mass with calcification and internal vascularity and fine needle aspiration (FNA) was performed.

 Macroscopic and Microscopic Description:  Cytology showed a cellular specimen predominantly composed of oncocytic, plasmacytoid and epithelioid myoepithelial cells, ductal epithelium and a small amount of chondro-mxyoid stroma. Some hyalinised material and necrotic debris was also seen. The majority of the myoepithelial and epithelial cells showed malignant features including marked cytological atypia with nuclear pleomorphism and occasional mitoses. These findings were consistent with carcinoma ex pleomorphic adenoma (PA). CT imaging showed no pulmonary lesions or evidence of metastatic spread. A repeat parotid FNA was performed that showed adenocarcinoma not otherwise specified (NOS); a radical parotidectomy and level II/III dissection was subsequently performed. Histology showed background benign PA with adjacent high-grade salivary duct carcinoma (SDC), showing typical cribiform growth pattern of epithelioid tumour cells and characteristic “Roman bridge formation”, which confirmed the diagnosis of carcinoma ex PA. There was prominent perineural spread, vascular invasion and resection margins were involved but lymph nodes showed no evidence of metastatic spread. Unfortunately the patient passed away 5 months following surgery.

Diagnosis:  

Discussion: Carcinoma ex PA is defined as an epithelial malignant neoplasm arising from a primary or recurrent PA. It accounts for 3.6% of all salivary gland neoplasms cases and approximately 12% of malignant salivary gland neoplasms1. The most common malignant component is a poorly differentiated adenocarcinoma, most frequently adenocarcinoma not otherwise specified (NOS) but sometimes salivary duct type, or an undifferentiated carcinoma2. Symptoms associated with malignant transformation of a PA include rapid growth of the parotid lump, pain, and facial nerve paralysis3; two of which were present in our case. Carcinoma ex PA represents a diagnostic challenge for cytopathologists and clinicians as patients may be asymptomatic or have clinical symptoms similar to that of a benign PA.

WHO sub-classifies carcinoma ex PA into: non-invasive; minimally invasive (≤1.5mm invasion beyond the capsule); and invasive (>1.5mm invasion beyond the capsule). Invasive carcinoma ex PA are extremely aggressive, have a poor prognosis and up to 70% of patients develop local or distant metastases. Those with SDC present with late stage disease and perineural spread, as in our case, is commonly seen2..

Histopathology is the gold standard for the diagnosis of carcinoma ex PA but early diagnosis and intervention can improve survival rates1. FNA cytology plays a vital role when used alongside radiological imaging and clinical assessment. FNA is easy to perform, cost effective and its use is widely accepted in diagnosing salivary gland lesions and differentiating between benign and malignant lesions3. However, its sensitivity in diagnosing carcinoma ex PA is low (ranging from 29% to 54%) thought mainly to be due to sampling error1, 4. This is highlighted in our case where initial FNA showed features of carcinoma ex PA but cytology of a subsequent sample showed adenocarcinoma NOS.

To diagnose carcinoma ex PA elements from both the benign PA and the malignant component need to be seen5. In cytology, cohesive clusters of benign ductal cells, a background of single myoepithelial cells, and a dense fibrillary stroma are essential for the diagnosis of background PA6. In combination with this, the presence of markedly atypical cells, an abnormal chromatin pattern, and necrosis are key in differentiating between a carcinoma ex PA and the possible differential of a PA with atypia3. Immunohistochemistry can be used in cases to confirm the diagnosis and to exclude other differentials including a metastatic lesion. In our case the combination of the clinical history, radiology and typical cytology findings led to a diagnosis of carcinoma ex PA and immunohistochemistry was not required. These findings were confirmed on histology and the malignant component identified as SDC.

Carcinoma ex PA is rare and it presents a diagnostic challenge for cytopathologists and clinicians. Our case highlights the importance of using cytology in conjunction with the clinical history and radiology to pre-operatively diagnose carcinoma ex PA and enable early surgical intervention. It is important to appreciate that cytology has its limitations and diagnostic pitfalls when diagnosing carcinoma ex PA and histopathology remains the gold standard for definitive diagnosis. 

Practice points

  • Carcinoma ex PA is rare, but early diagnosis and intervention is important as tumours are generally high-grade and patients have a poor prognosis.
  • Diagnosis of carcinoma ex PA by cytology is difficult and requires demonstration of benign and malignant components. Correlation with clinical and radiological findings is always necessary.
  • Pleomorphic adenoma can display mild atypia, however significant atypia, abnormal chromatin pattern and necrosis can help differentiate with carcinoma ex PA.

References

[1] Antony J, Gopalan V, Smith RA, Lam AK. Carcinoma ex pleomorphic adenoma: A comprehensive review of clinical, pathological and molecular data. Head Neck Pathol 2012; 6:1-9 [2] Barnes L, Eveson JW, Reichart P, Sidransky D, editors. World health organisation classification of tumours. Pathology and genetics of head and neck tumours. Lyon: IARC Press; 2005 [4] Klijanienko J, El-Naggar AK, Vielh P. Fine-needle sampling findings in 26 carcinoma ex pleomorphic adenomas: diagnostic pitfalls and clinical considerations. Diagn Cytopathol. 1999;21:163–166 [3] Singh K, Agarwal C, Pujani M, Verma P, Chauhan V. Carcinoma ex pleomorphic adenoma: A diagnostic challenge on cytology. Diagn Cytopathol. 2017; 45 (7):651-654 [5] Yamada S, Nabeshima A, Tabata T, Guo X, Tasaki T, Wang K-Y, Shimajiri S, Sasaguri Y. Invasive salivary duct carcinoma ex pleomorphic adenoma of the parotid gland: a teaching case giving rise to the genuine diagnostic difficulty on an inadequate cytology specimen. Diagnostic Pathology (2012); 7:61 [6] Gahine R, Sudarshan V, Hussain N, Krishnani C. Pleomorphic adenoma: A diagnostic pitfall in the diagnosis of salivary gland lesions on FNAC: Case reports with review of the literature. CytoJournal (2010);7:17

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