Abstract
Background
Endoscopic sinus surgery has become the mainstay in surgical treatment of sinusitis and nasal polyps. While rare, diagnostic discrepancies or pathological contamination during routine specimen analysis has been described. Thus, an accurate diagnosis and indication for surgery are mandatory before proceeding with surgical intervention.
Methods
We present the case of a 40-year-old female patient who underwent endoscopic sinus surgery (ESS) for chronic sinusitis without nasal polyposis and fragments of squamous cell carcinoma (SCC) were found in the pathology specimen.
Results
We propose an algorithm to help guide physicians presented with a tissue diagnosis that does not match the clinical scenario. Moreover, we discuss strategies to help prevent medical errors and the importance of DNA genetic analysis in this situation.
Conclusion
When an unexpected diagnosis occurs, the pathology slides should be reviewed for a second opinion. If the unexpected diagnosis is confirmed, the tissue should undergo STR genetic analysis to ensure against tissue contamination.
1
Background
Sinonasal cancers are rare and make up roughly 3% of all tumors arising from the upper digestive tract . Furthermore, they constitute 5% of all head and neck cancers and less than 1% of malignancies overall . They are often a challenge to diagnose because the presenting symptoms and their appearance are similar to those found in benign, inflammatory and even autoimmune processes. Sinonasal malignancies can be asymptomatic as well, adding to their diagnostic difficulty. Treatment of sinonasal malignancies varies based on multiple variables including histology, size, and location. Strategies often include a combination of surgery and radiotherapy that require precise location of the tumor to target therapy, maximize efficacy, and minimize morbidity.
Usually, the clinical assessment matches the described pathology and appropriate treatment ensues. However, occasionally the clinical picture does not match the histopathologic analysis even after careful microscopic evaluation. We present the case of a 40-year-old female patient who underwent endoscopic sinus surgery (ESS) for chronic sinusitis without nasal polyposis and fragments of squamous cell carcinoma (SCC) were found in the pathology specimen. We propose an algorithm to help guide physicians presented with a tissue diagnosis that does not match the clinical scenario. Moreover, we discuss strategies to help prevent medical errors and the importance of DNA genetic analysis in this situation.
2
Methods
A 40-year-old female with chronic sinusitis without nasal polyposis and turbinate hypertrophy continued to have symptoms despite medical therapy and underwent ESS and turbinate reduction in November 2012 by a referring physician. ( Fig. 1 ) A bilateral anterior ethmoidectomy, maxillary antrostomy and submucous resection of the inferior turbinates were performed. The procedure was uncomplicated and no suspicious lesions were encountered. The removed sinus contents were sent to pathology for routine histological analysis. Unfortunately, the right and left sinus contents were not separated as per the usual protocol. The pathology report identified “detached fragments of squamous cell carcinoma in situ arising in association with squamous dysplasia and chronic sinusitis.”
The patient was watched closely with serial endoscopies and a follow-up CT scan was performed 3 months post-operatively that did not identify an obvious sign of malignancy. Genetic analysis of the tissue was performed using short tandem repeat (STR) analysis based on the Combined DNA Index System (CODIS). This revealed the squamous cell carcinoma tissue was a contaminant from another patient. The patient ultimately underwent revision surgery for a maxillary sinus cyst associated with dental disease approximately 2 years later that did not reveal malignancy. ( Fig. 2 ).
2
Methods
A 40-year-old female with chronic sinusitis without nasal polyposis and turbinate hypertrophy continued to have symptoms despite medical therapy and underwent ESS and turbinate reduction in November 2012 by a referring physician. ( Fig. 1 ) A bilateral anterior ethmoidectomy, maxillary antrostomy and submucous resection of the inferior turbinates were performed. The procedure was uncomplicated and no suspicious lesions were encountered. The removed sinus contents were sent to pathology for routine histological analysis. Unfortunately, the right and left sinus contents were not separated as per the usual protocol. The pathology report identified “detached fragments of squamous cell carcinoma in situ arising in association with squamous dysplasia and chronic sinusitis.”
The patient was watched closely with serial endoscopies and a follow-up CT scan was performed 3 months post-operatively that did not identify an obvious sign of malignancy. Genetic analysis of the tissue was performed using short tandem repeat (STR) analysis based on the Combined DNA Index System (CODIS). This revealed the squamous cell carcinoma tissue was a contaminant from another patient. The patient ultimately underwent revision surgery for a maxillary sinus cyst associated with dental disease approximately 2 years later that did not reveal malignancy. ( Fig. 2 ).
3
Results
The clinical judgment of the surgeon is an essential component to obtaining an accurate diagnosis and directing treatment. This begins with a careful history and physical examination. In patients with sinonasal complaints, this usually includes office nasal endoscopy that has video recording capabilities, which may prove useful for future review. Additional diagnostic modalities such as radiographic or nuclear imaging, serum laboratory tests, and preoperative tissue samples help compliment the history and physical examination. Careful documentation of medical management, surgical indications, and interpretations of pre-operative testing is important for both patient safety and legal protection. Ideally, the findings on work-up are congruent, but the physician should be careful for inconsistencies throughout the care of the patient.
Intra-operative measures that prevent medical errors begin with patient identification and a thorough pre-operative ‘time-out’. Patient films should be verified along with images used for stereotactic navigation. Intra-operative pictures and video recording may prove helpful for documentation that can be reviewed and shared with treating physicians. All specimens should be carefully reviewed and labeled as either right or left before leaving the operating room. A consensus exists that suspicious sinonasal lesions should be biopsied and sent for histopathologic review. Findings suggestive of a suspicious lesion include but are not limited to unilateral nasal masses or polyps, cortical erosion or expansion beyond the paranasal sinuses on imaging, associated cranial neuropathies, septal perforation, a history of sinonasal malignancy or local radiation treatment. Histophathologic analysis can identify processes such as malignancy, either benign or malignant, or inflammatory conditions like sarcoid, Churg–Strauss, or granulomatosis with polyangitis. Alternatively, the routine examination of septal bone and cartilage along with turbinate tissue is likely not warranted or cost effective as the yield is exceedingly low .
However, a debate exists as to whether routine sinus specimens should be sent for pathologic analysis in the setting of bilateral chronic sinusitis. At one end of the spectrum, it has been suggested that routine pathologic examination of sinus contents yields few unexpected and management-changing diagnosis . Studies identify a rate of an unsuspected pathologic diagnosis between 0.23 and 1.1% for patients with chronic sinusitis . There is also the potential for contamination, like in this case, that may lead to unnecessary testing, surgery, and financial loss. However, sinonasal malignancy can masquerade as inflammatory disease both on examination and imaging. Studies identify high rates (~ 16%) of a change in diagnosis from an office biopsy and a completely analyzed pathologic specimen for a unilateral nasal mass . Moreover, most series analyzing the incidence of an occult diagnosis have inherent limitations and biases of a retrospective study and are written from experts in the field. Thus, community physicians who are not as experienced in deciphering between high and low risk patients likely have a higher rate of an unexpected diagnosis. If 257,000 outpatient sinus procedures were performed in the United States in 2006, then it could be postulated that the annual number of cases with an unsuspected diagnosis may be between 500 and 2500 . Moreover, cost analysis shows that litigation expenses from missing a malignancy outweigh the financial burden of excessive histopathologic costs . While sending tissue from patients with sinusitis may represent good clinical practice, the current body of literature is not strong enough to mandate the routine pathologic analysis for patients with bilateral chronic sinusitis as the standard of care.
Specimen identification problems happen when specimens are mislabeled and occur at an alarming rate of 6% of accessioned cases. Extraneous tissue contaminants are found in 0.67–2.9% of slides . In a prospective study, 30% of these contaminants were abnormal or neoplastic. Specimen problems can occur throughout the process either by specimen mix-ups, cross contamination, floaters, or carryover artifacts. Short tandem repeat (STR) analysis is a DNA-based test used for specimen identity testing. The Federal Bureau of Investigation (FBI) in the United States is the leader in developing DNA typing technology that includes the Combined DNA Index System (CODIS). The STR analysis using the CODIS loci is commercially available and has clinical applicability for resolution of specimen identification issues. A “DNA timeout” has been proposed to analyze STRs in pathologic specimens when an aggressive medical or surgical intervention is recommended based on the findings. In this case, DNA testing proved valuable in identifying the tissue as a contaminant.
Diagnostic discrepancy rates are another issue and have ranged from 1 to 53% for surgical pathology studies and from 17 to 60% for cytopathology studies . A study in 1999 by Kronz et al. investigated mandatory second opinion of outside pathology by the treating institution and found a high number of discordant diagnoses leading to altered therapeutic intervention . In response to this study, Time magazine wrote an article calling for mandatory second opinion pathology review on all malignant diagnoses . Epstein et al. showed that mandatory review of prostate biopsies before radical prostatectomy was cost effective and for every one dollar spent on pathological review, nearly two dollars was saved on reduced surgical intervention . This did not take into account cost savings from lost wages or potential litigation.
Second opinion pathology review may be sensible for head and neck malignancies given their high level of complexity and diversity. Numerous studies have implicated the head and neck region as an area of high-risk for diagnostic error and could benefit from second opinion . It is our opinion, as well as others, that before undertaking any major therapeutic endeavor, a second opinion for head and neck oncologic cases makes good clinical and risk management sense especially if it was performed at an outside facility .
We propose that patients who have an unsuspected diagnosis on pathologic analysis have the slides reviewed for a second opinion. If there is agreement between pathologists, then the tissue should undergo STR analysis for DNA identification. This would obviate the need for unnecessary testing, radiation exposure, surgery, financial loss, agony, and potential litigation associated with a specimen identification error. If DNA testing confirms an unsuspected lesion, then the patient should undergo the necessary work-up for the disease. For example, if a tumor such as an inverted papilloma is identified in the specimen, then serial endoscopies with long-term surveillance and repeat imaging are indicated. Directed biopsies or completion sinus surgery is another option for aggressive or malignant lesions. Unfortunately, the precise location of the lesion is often hard to identify in cases of malignancy. These patients require close surveillance along with the appropriate work-up and definitive treatment. This may include serial examinations with endoscopy, imaging, potentially revision/completion surgery with directed biopsies, and even radiation or chemotherapy. Studies are limited with good recommendations in this scenario and are disease specific. ( Fig. 3 ).
