Papillary microcarcinoma of the thyroid.
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Carcinoma, Papillary↗
Biomedical subjects
Ashok R Shaha
Publications and source records attributed to Ashok R Shaha.
FDG-PET detected thyroid incidentalomas: need for further investigation?
BACKGROUND: Incidental thyroid abnormalities are increasingly detected in patients undergoing PET scans. The aim of this study was to review our experience with the management of PET detected thyroid incidentalomas in a large single institution series. METHODS: All PET scans performed from May 2003 to July 2005 were reviewed and patients with incidental thyroid abnormalities were identified. From this group, patients that underwent further investigation were analyzed. Data relating to PET scan findings, FNA diagnoses, operative details, and histopathology was reviewed. RESULTS: In 8,800 patients, 16,300 PET scans were performed of whom 263 patients (2.9% of patients and 1.6% of PET scans) had findings positive for thyroid abnormality. Thyroid malignancy was noted in 42% (24 patients) of the 57 patients that underwent FNA. In the group of 27 patients that were subjected to operative intervention, 74% (20 patients) were noted to have a malignant diagnosis. The final histopathology revealed primary thyroid carcinoma in all these 20 patients (19 patients with papillary carcinoma and one patient with primary thyroid lymphoma). The factors that correlated with an increased risk of malignancy were the presence of physical finding (p = 0.01) and focal (p < 0.01) or unilateral uptake (p < 0.01) on PET scan. The average SUV was not useful in differentiating benign (9.2) from malignant lesions (8.2, p = 0.7). CONCLUSIONS: PET detected incidental thyroid abnormalities are rare. In patients with positive PET scan findings and suspicious features, the incidence of primary thyroid malignancy is very high. These patients warrant further investigation followed by possible operative intervention.
Biopsy, Fine-Needle↗
Options for salvage after failed initial treatment of anterior vocal commissure squamous carcinoma.
Persistence or recurrent cancer in the anterior commissure (AC) after primary radiotherapy may remain localized to its pretreatment anatomical site. If so, endoscopic CO(2) laser excision, in experienced hands, may achieve complete tumor excision and result in cure for many patients. Occasionally, second and third recurrences may be similarly salvaged by further endoscopic surgery. The use of the vertical hemilaryngectomy is an alternative treatment for similar localized lesions, with a higher first time surgical tumor eradication rate, but with a more protracted hospitalization and a less satisfactory voice and swallowing outcome. In both types of such surgical salvage, CT scanning must demonstrate no evidence of cartilage invasion or destruction. When there is evidence of minimal thyroid cartilage invasion, then the supracricoid partial laryngectomy is an alternative conservation option, and is likely to result in a cure, with the retention of a voicing larynx without a stoma. When the tumor has increased in size from the original pretreatment dimension and/or site, then imaging must be used to identify possible cartilage invasion, in which case the likelihood of tumor eradication by endoscopic or external vertical partial laryngectomy is highly unlikely. The indications for the routine use of total laryngectomy for the treatment of recurrent or persistent cancer involving the AC must be reviewed; there is current evidence that cure can be achieved by a less radical procedure. However, total laryngectomy may remain the only treatment option for advanced or aggressive first time recurrence, or in patients who develop subsequent recurrence following previous less aggressive surgery (endoscopic or external).
Carcinoma, Squamous Cell↗
Primary treatment of the anterior vocal commissure squamous carcinoma.
Squamous cell carcinoma may involve the anterior commissure (AC) area of the laryngeal glottis, and can be grouped morphologically into four groups; (1) tumor confined to the AC, (2) tumor involving one cord and the AC, (3) tumor involving the AC and a portion of both vocal cords, and (4) tumor involving a greater part of one cord and crossing over to involve a variable length of the other cord. Some of these patients when evaluated by imaging, either CT and/or MRI, may demonstrate thyroid cartilage erosion or involvement, thereby upstaging a T1a, T1b into a T3 or a T4 glottic cancer. The majority of patients treated by radiotherapy have only been staged clinically, and hence a failure or recurrence rate of 15%. In patients treated surgically by endoscopic or external surgery, the local recurrence rates are similar at 15%. Therefore, future reporting of patients treated with AC involvement should be staged radiologically, to include CT or MRI, and documentation of the treatment results be reported in subgroups, according to whether there is no cartilage involvement, inner-table cartilage erosion, or through-and-through cartilage invasion. Should endoscopic cordectomy be used, then the type of surgery performed should be based on the classification as suggested by the European Laryngological Society. The use of the above recommendations would allow for more meaningful results to be reported and for cause specific analysis of failure of treatment techniques applied.
Carcinoma, Squamous Cell↗
Neck dissection: then and now.
The significance of metastatic disease in the lymph nodes of the neck as a critical independent prognostic factor in head and neck cancer has long been appreciated. Although 19th century surgeons attempted to remove involved cervical lymph nodes at the time of resection of the primary cancer, a systematic approach to en bloc removal of cervical lymph node disease, described in detail by Jawdyński in 1888 and popularized and illustrated by Crile in the early 20th century, provided consistent and more effective treatment, and forms the basis of our current techniques. During the first half of the 20th century, developments included preservation of the accessory nerve in selected cases, elective neck dissection performed in association with resection of various primary tumors, bilateral neck dissection and limited neck dissection. The greatest impetus to the status of radical neck dissection came from Martin, whose technique consisted of resection of all lymph nodes from level I-V together with the accessory nerve, internal jugular vein, sternocleidomastoid muscle and various other structures in a single block of resected tissue. Martin's technical precepts were followed until the latter part of the 20th century when modifications in technique began to find general acceptance. The first description of an effective technique of modified radical neck dissection was published in Spanish by Suárez, in 1963. This technique, which preserves important structures, such as the internal jugular vein, sternocleidomastoid muscle and accessory nerve, was refined and popularized by various authors who published their results in the English language literature during the period from 1964 through 1990 and beyond. Modified or "functional" neck dissection avoids much of the morbidity of radical neck dissection while achieving equivalent degrees of control of regional disease in properly selected cases. By the late 20th century, the concept of selective neck dissection, consisting of resection of only the nodal groups at greatest risk for metastasis from a given primary site, was studied and developed. These limited dissections are now widely employed for elective, and in properly selected cases, therapeutic treatment and staging of the neck, and have been proposed for limited cervical recurrences after various chemoradiation protocols. Prospective studies have demonstrated similar rates of neck recurrence and survival after elective selective neck dissection compared to elective modified radical neck dissection. Other modifications and factors applied to treatment of cervical lymph node disease include the use of adjuvant and neo-adjuvant radiation and chemotherapy, a revised system for classification of neck dissections, the identification of various adverse prognostic factors such as extracapsular spread and extranodal soft tissue deposits, application of sentinel lymph node biopsy to staging of the neck, the use of immunohistochemical and molecular techniques for identification of lymph node metastases not detectable by light microscopy, and the possibility of endoscopic neck dissection. The authors conclude that neck dissection, as evolved over the past century, is a fundamental tool in management of patients with head and neck cancer, but is still a work in progress.
Head and Neck Neoplasms↗
Tumours of familial origin in the head and neck.
Individuals with inherited cancer syndromes are at significant risk of developing both benign and malignant tumours as a result of a germline mutation in a specific tumour suppressor gene. Tumours of familial origin are a rare event in the head and neck but despite this, they deserve a growing interest. Familial paragangliomas are most of the time limited to the paraganglionar system, but also may be part of different syndromic associations. Since early detection of paragangliomas reduces the incidence of morbidity and mortality, genotypic analysis in the search of SDHB, SDHC and SDHD mutations in families of affected patients plays a front-line diagnostic role, leading to more efficient patient management. Multiple endocrine neoplasias type 1 are characterized by the simultaneous occurrence of at least two of the three main related endocrine tumours: parathyroid, enteropancreatic and anterior pituitary. These tumours arise from inactivating germline mutations in the MEN-1 gene. No clear correlation of MEN-1 genotype with genotype has emerged to date, and MEN-1 mutation testing in tumours is not used clinically because it have not implications for tumour staging. Multiple endocrine neoplasia type 2 is due to a germline mutation in the RET proto-oncogene. Hallmarks of MEN-2A (the commonest phenotypic variant) include medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. The most central clinical difference with MEN-1 is that the associated cancer can be prevented or cured by early thyroidectomy in mutation carriers. Individuals with neurofibomatosis type 1 present early in life with pigmentary abnormalities, skinfold freckling and iris hamartomas, as result of NF1 gene mutation. Neurofibromatosis 2 is caused by inactivating mutations of the NF2 gene, and is characterized by the development of nervous system tumours (mainly bilateral vestibular schwannomas), ocular abnormalities, and skin tumours. The molecular genetic basis of nasopharyngeal carcinomas remains unknown, but there is evidence for the linkage of these tumours to chromosome 3p. Finally, the high rate of p16 mutations in squamous cell carcinomas and the association of p16 with familial melanoma propose p16 as an ideal candidate gene predisposing to familial squamous cell carcinomas. The elucidation of the cellular processes affected by dysfunction in familial tumours of the head and neck may serve to identify potential targets for future therapeutic interventions.
Carcinoma, Squamous Cell↗
Sentinel Lymph Node Biopsy for Cutaneous Head and Neck Melanoma: Mapping the Parotid Gland.
BACKGROUND: Sentinel lymph node biopsy (SLNB) for primary cutaneous head and neck melanoma (CHNM) has been shown to be successful and is the current standard of care for intermediate-thickness melanoma. We evaluated our experience with CHNM associated with SLNB mapping to the region of the parotid gland. METHODS: Retrospective review of a prospectively collected melanoma database identified 1014 CHNMs. Two-hundred twenty-three patients underwent SLNB, and 72 (32%) had mapping in the region of the parotid gland between May 1995 and June 2003. RESULTS: The mean number of SLNs per patient was 2.5. A sentinel lymph node (SLN) was successfully identified in 94% of patients, and in 12%, the SLN was positive for metastatic disease. Biopsy of intraparotid SLNs was performed in 51.4% and of periparotid SLNs in 26.4%, and a superficial parotidectomy was performed in 22.2%. Ten patients were found to have lymph nodes in the parotid region with metastatic disease (eight identified by SLNB), and two (20%) patients developed intraparotid lymph node recurrence in the setting of a negative SLNB. Same-basin recurrence in SLN-negative patients was 3.3% with a median follow-up of 26 months. Facial nerve dysfunction was identified in seven (10%) patients. Facial nerve function returned to preoperative status in all patients. CONCLUSIONS: SLNB for patients with primary CHNM mapping to the parotid gland can be performed with a high degree of accuracy and a low morbidity consisting of temporary facial nerve paresis.
Adolescent↗
Opening the "gift box": a systematic approach to expose the thyroid and superior thyroid vessels in complicated thyroid surgery.
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Humans↗
Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm.
PURPOSE: Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor. Cetuximab has activity in squamous cell carcinoma and enhances both chemotherapy and radiotherapy. We conducted a pilot phase II study of a new combined-modality paradigm of targeted therapy (cetuximab) with chemoradiotherapy. PATIENTS AND METHODS: Eligible patients had stage III or IV, M0, squamous cell head and neck cancer. Treatment included concomitant boost radiotherapy (1.8 Gy/d weeks 1 to 6; boost: 1.6 Gy 4 to 6 hours later weeks 5 to 6; 70 Gy total to gross disease), cisplatin (100 mg/m2 intravenously weeks 1 and 4), and cetuximab (400 mg/m2 intravenously week 1, followed by 250 mg/m2 weeks 2 to 10). RESULTS: Twenty-two patients were enrolled (median age, 57 years; range, 41 to 72 years; median Karnofsky status, 90%; range, 70% to 90%; oropharynx primary tumor, 59% of patients; T4, 36%; N2/3, 77%; stage IV disease, 86%). One patient did not receive study treatment because of an ineligible diagnosis. The severity of expected, acute toxicities was typical of concurrent cisplatin and radiotherapy alone. Grade 3 or 4 cetuximab-related toxicities included acne-like rash (10%) and hypersensitivity (5%). However, the study was closed for significant adverse events, including two deaths (one pneumonia and one unknown cause), one myocardial infarction, one bacteremia, and one atrial fibrillation. With a median follow-up of 52 months, the 3-year overall survival rate is 76%, the 3-year progression-free survival rate is 56%, and the 3-year locoregional control rate is 71%. CONCLUSION: This regimen is not currently recommended outside of the clinical trial setting. Further investigation of its safety profile is needed. However, preliminary efficacy is encouraging, and further development of this targeted combined-modality paradigm is warranted.
Adult↗
Anaplastic thyroid carcinoma: biology, pathogenesis, prognostic factors, and treatment approaches.
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors known to affect humans and carries a dismal prognosis. Our primary aim was to review its epidemiology, biology, risk factors, and prognostic indicators. We also reviewed the individual and combined roles of surgery, radiotherapy, chemotherapy, and newer therapeutic options in the management of ATC. METHODS: An extensive literature review was conducted to include all published reports on ATC. The changing trends in the management of anaplastic thyroid cancer were analyzed to summarize the current practice of management of ATC. RESULTS: Although ATC is rare, there has been a decline in its incidence worldwide. ATC accounts for more than half of the 1200 deaths per year attributed to thyroid cancer. Long-term survivors are rare, with >75% and 50% of patients harboring cervical nodal disease and metastatic disease, respectively, at presentation. ATC can arise de novo or from preexisting well-differentiated thyroid cancer. Surgical management has shifted from tracheostomy only for palliation to curative resection when possible. Tracheostomy is performed for impending obstruction rather than for prophylaxis. Radiotherapy has evolved from postoperative administration only to preoperative treatment, combining preoperative and postoperative treatment and using higher doses, along with hyperfractionating and accelerating dose schedules. Chemotherapy has changed from monotherapy to combination therapy, and newer drugs such as paclitaxel show promise. Similarly, novel angiogenesis-inhibiting agents are currently being used, with early reports of some benefit. CONCLUSIONS: Despite multimodality approaches, ATC still carries a dismal prognosis. This should provoke innovative strategies beyond conventional methods to tackle this uniformly lethal disease.
Carcinoma↗
Results of surgical salvage after failure of definitive radiation therapy for early-stage squamous cell carcinoma of the glottic larynx.
OBJECTIVE: To report the outcome of surgical salvage performed for early-stage squamous cell carcinoma of the glottic larynx that recurred or progressed after definitive radiotherapy. DESIGN: Retrospective outcome analysis. SETTING: Tertiary referral center specializing in head and neck cancer. PATIENTS: Forty-three patients who underwent salvage surgery after definitive radiation therapy for early-stage (T1-T2) glottic cancer were identified from a preexisting database of 662 patients with squamous cell carcinoma of the larynx treated at Memorial Sloan-Kettering Cancer Center between the years 1984 and 1998. The T stage at initial presentation was T1 in 20 (18%) and T2 in 23 (32%). Twenty-one patients (49%) were amenable to salvage partial laryngectomy (SPL), but 22 (51%) required salvage total laryngectomy (STL). Details on patient characteristics, tumor characteristics, postoperative complications, and survival outcome were extracted from the database. MAIN OUTCOME MEASURES: Overall survival, disease-specific survival, neck recurrence-free survival, and distant recurrence-free survival. RESULTS: No postoperative death occurred following salvage surgery. The overall incidence of complications was 21%, with no difference between the SPL and STL groups. Patients who required STL had poorer overall survival and disease-specific survival compared with patients who required SPL (overall survival, 50% vs 89%; P = .003; disease-specific survival, 51% vs 93%; P = .002). This difference in survival was associated with a poorer neck recurrence-free survival and distant recurrence-free survival in the STL group compared with the SPL group (neck recurrence-free survival, 80% vs 100%; P = .04; distant recurrence-free survival, 71% vs 93%; P = .06). Univariate analysis showed that age and clinical T stage at recurrence were predictors of overall survival, disease-specific survival, and distant recurrence-free survival. CONCLUSIONS: Careful selection of patients with early-stage glottic tumors that recur or progress after radiation allows patients to be successfully treated by partial laryngectomy with excellent survival outcome. However, despite an aggressive policy of performing partial laryngectomy when feasible, up to 50% of patients will require a total laryngectomy owing to progression of disease. These patients have poorer survival outcomes manifested by local, regional, and distant disease progression.
Adult↗
Planned neck dissection following chemoradiotherapy for advanced head and neck cancer: is it necessary for all?
In the absence of large-scale randomized trials evaluating dissection versus observation of the involved neck after neoadjuvant chemoradiotherapy, there is a need to collect data that will either support or ultimately refute a role for planned posttreatment neck dissection. A significant percentage of patients with extensive (N2 or N3) neck disease who demonstrate a complete response to chemoradiation therapy may harbor residual occult metastases, and identification of this subset of patients remains a clinical challenge. Because surgical salvage rates are greatly diminished when occult nodal disease becomes clinically manifest, planned posttreatment neck dissection is advocated but may not be necessary in all patients. The role of positron emission tomography chemoradiotherapy (PET-CT) in this scenario remains unproven but holds promise in being able to identify which patients may be harboring residual disease in the neck after chemoradiotherapy. The implementation of as yet unidentified molecular tumor markers in combination with PET-CT may ultimately prove to be effective in identifying patients who will best benefit from posttherapy neck dissection. Correlation of imaging results and pathologic node status will be important in determining the accuracy and, therefore, the value of this imaging modality for predicting the presence or absence of residual disease.
Carcinoma, Squamous Cell↗
Clinical curiosity: cribriform-morular variant of papillary thyroid carcinoma.
BACKGROUND: There is an increasing awareness of the association of papillary thyroid carcinoma and familial adenomatous polyposis (FAP). Although the incidence is rare, most tend to occur in women. Several authors have described a distinctive histologic variant of papillary thyroid carcinoma, the cribriform-morular variant, which is associated with FAP but also may be encountered in patients with non-FAP. This diagnosis may precede the symptoms of colorectal polyposis. METHODS: A healthy 36-year-old woman was seen with a left thyroid nodule, and a 34-year-old woman with FAP was seen with a right thyroid nodule; both masses were suspicious for papillary thyroid carcinoma. Both patients underwent total thyroidectomy. RESULTS: Pathologic examination of both specimens revealed papillary thyroid carcinoma, cribriform-morular variant. The first patient subsequently underwent colonoscopy, which was negative for polyposis. CONCLUSIONS: Patients diagnosed with the cribriform-morular variant of papillary thyroid cancer should be screened for the presence of FAP.
Adenomatous Polyposis Coli↗
Molecular diagnostic methods in the diagnosis and follow-up of well-differentiated thyroid carcinoma.
Thyroid cancers are the most common endocrine malignancies and are being diagnosed with increased frequency in modern clinical practice. Among other diagnostic modalities, fine-needle aspiration (FNA) biopsy of clinically suspicious thyroid nodules is becoming increasingly popular. Preliminary investigations have suggested that molecular diagnostic assays using tumor-specific markers may improve the sensitivity and accuracy of FNA and so may be expected to reduce the frequency of open surgical procedures by identifying those patients with demonstrably benign lesions who do not require definitive surgical excision of their lesions for diagnosis. At the same time, thyroid-specific mRNA assays (especially thyroglobulin mRNA testing) have been used by investigators in the postoperative follow-up of patients with thyroid cancer as a potential means of detecting tumor recurrence in the peripheral blood. Although these studies have not all reported unqualified successes--indeed, some problems based on both technical and biologic limitations have been identified-these assays still hold out the possibility that potentially important new advances in the management of patients with well-differentiated thyroid cancer may be offered by these and other molecular diagnostic methods.
Biomarkers, Tumor↗
Invited commentary: Vocal cord evaluation in thyroid surgery.
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Humans↗
Late-onset medullary carcinoma of the thyroid: need for genetic testing and prophylactic thyroidectomy in adult family members.
OBJECTIVE: Sporadic late-onset medullary carcinoma of the thyroid is quite rare. Usually, the patient presents with a thyroid mass or neck node metastasis along with high levels of calcitonin and preoperative fine needle aspiration biopsy suggestive of medullary carcinoma of the thyroid. The role of genetic testing in such individuals, along with testing of other family members, remains somewhat unclear at this stage, especially in patients presenting with familial medullary thyroid carcinoma. Genetic testing with RET proto-oncogene mutational studies is very popular in familial medullary thyroid carcinoma, especially in children, with routine prophylactic thyroidectomy. However, its indications in adults remain unclear at this time. CASE STUDY: Recently, a 69-year-old woman presented with a thyroid mass and underwent total thyroidectomy and central compartment dissection. She was found to have medullary carcinoma of the thyroid. The patient had four children, three of whom were found to have a RET mutation similar to their mother's, V804M. In view of the RET mutation, the three children were offered prophylactic thyroidectomy at ages 42, 45, and 47. The patient's son was noted to have extensive C-cell hyperplasia in both lobes of the thyroid. The other two individuals had benign pathology with no evidence of C-cell hyperplasia. CONCLUSIONS: There is no definite consensus of opinion about the need for prophylactic total thyroidectomy in adults with RET mutation. The rarely reported 804 mutation is, however, a predictor of medullary carcinoma of the thyroid. One individual in this group had extensive C-cell hyperplasia, suggesting that he would have developed medullary carcinoma of the thyroid in the future. Prophylactic thyroidectomy should be recommended in patients with RET mutation and a family history of medullary carcinoma of the thyroid; however, its role in adult family members needs to be evaluated with larger registry of prophylactic thyroidectomy. Whether these adults with rare 804-mutation could be observed and followed with serial calcitonin, ultrasound, or calcitonin stimulation tests remains to be studied.
Adult↗
Poorly differentiated and anaplastic thyroid cancer.
BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic (undifferentiated) thyroid carcinoma (ATC) comprise a small subset of thyroid tumors that are associated with a poor prognosis and account for a significant portion of the morbidity and mortality related to thyroid cancer. Since management strategies vary between these two entities, it is important for clinicians to be able to differentiate PDTC from ATC. METHODS: We reviewed the literature on PDTC and ATC and compared clinical and histopathologic features important in defining the disease process. RESULTS: Both PDTC and ATC display aggressive behavior with increased locoregional and distant disease. In most cases, patients are older and have large, locally advanced tumors. PDTC may represent an intermediate entity in the progression of well-differentiated thyroid carcinoma to ATC. The use of surgical management may be curative or palliative and differs between PDTC and ATC. The roles of radiotherapy and chemotherapy have not been well described. CONCLUSIONS: PDTC and ATC are rare diseases that carry a poor prognosis. Recognition of their different clinicopathologic features is important to the optimal management of these tumors.
Carcinoma↗