Can we tell the site of origin of metastatic squamous cell carcinoma? An immunohistochemical tissue microarray study of 194 cases.

To the workup of metastatic squamous cell carcinoma (SCC) of unknown primary, we studied an immunohistochemical panel including thyroid transcription factor (TTF-1), napsin A, villin, CDX-2, K903, CK5/6, p63, p16, CK7, and CK20. Using tissue microarray, we compared 194 SCC cases from the following sites: 35 lung, 34 skin, 14 cervix, 4 vagina, 16 vulva, 8 penis, 9 anus, 3 rectum, 10 esophagus, 4 bladder/urethra, and 57 SCC from various head and neck sites. p63 and K903 stained positively in 100% of cases, and CK5/6 in nearly 100% of cases, with the exception of 1 lung. CK7 was positive in 31.6% of all cases, with varying positivity according to the site. CK20 was negative in all cases except 1 lung. Napsin A was positive in 25.8% of lung, 7.7% of skin, 37.5% of penis, and 13.3% of tongue, and negative in all other sites. TTF-1 was positive only in 1 lung. p16 positivity ranged from 21.43% in vulva, to 75% in vagina and anus, and it was negative in lung, penis, bladder/urethra, and some head and neck. CDX-2 was negative in all cases except 1 vulva. Villin was negative in all cases. We conclude that immunohistochemistry has very limited value in determining the primary site of metastatic SCC. If lung is in the differential versus head and neck, esophagus, anorectal, or genital SCC, a panel including TTF-1, napsin A and p16 may be helpful, since positive TTF-1 and/or napsin A would favor lung primary, and positive p16 would favor an extrapulmonary site.

Comparison of EUS-guided FNA and Trucut biopsy for diagnosing and staging abdominal and mediastinal neoplasms.

The objective of this study was to evaluate endoscopic ultrasound Trucut biopsy (TCB) specimens and compare these findings to fine needle aspiration (FNA) specimens for the diagnosis of neoplasia. FNA and TCB specimens were reviewed in blinded fashion by a cytopathologist from patients (N = 93) who had EUS-guided FNA and TCB specimens collected between July 2000 and January 2005. Specimens were categorized as nondiagnostic, negative, suspicious for stromal neoplasm, suspicious for malignancy, positive for stromal neoplasm, or positive for malignancy. Standard final diagnosis based on clinical and/or pathologic follow-up was available for 86 of 93 patients. The final diagnoses comprised malignancy (n = 55), stromal neoplasm (n = 19), and benign findings (n = 12). The combination of FNA and TCB results combined were significantly (P < 0.001) more sensitive that FNA alone for the detection of both malignancy (78% vs. 55%) and stromal neoplasia (79% vs. 19%) without a significant change in overall specificity (92% vs. 100%, P = 1.00). A positive FNA specimen with a negative/nondiagnostic TCB result was established in seven patients with malignancy. A positive TCB diagnosis with a negative/nondiagnostic FNA result was noted in five patients with malignancy. A suspicious FNA result was upgraded to positive in conjunction with TCB specimen evaluation in eight patients with malignancy. The results of this study suggest that TCB is a useful adjunctive technique when used in tandem with FNA for malignancy and stromal neoplasia detection. Additional data are needed to firmly establish practice guidelines for the use of EUS-guided TCB specimens in clinical practice.

A multi-institutional survey of critical diagnoses (critical values) in surgical pathology and cytology.

Critical values (CVs) are well established in clinical pathology, and an analogous concept has recently been suggested in anatomic pathology, with the terminology of critical values, or, alternatively, critical diagnoses (CDs). To better identify anatomic pathology CVs, a survey was sent to 225 members of the Association of Directors of Anatomic and Surgical Pathology (ADASP) for grading 17 possible surgical pathology and 18 possible cytology CVs. There were 73 responses for surgical pathology and 57 for cytology. The majority of the respondents believed in the concept of CVs in anatomic pathology. There was good agreement concerning most of the possible CVs, although there were differences of opinion for some diagnoses. Several additional CVs were suggested, and there was discussion of the best terminology for CVs, degree of urgency, and appropriate notification documentation. A few respondents expressed concern about medicolegal implications. Based on the results of this survey, an ADASP committee has developed national guidelines for CDs (CVs) in surgical pathology and cytology.

Diagnostic and prognostic utility of molecular markers in synchronous bilateral breast carcinoma.

Histologic criteria have a limited role in determining whether the synchronous bilateral breast carcinomas represent two primaries or a metastasis to the contralateral breast. We studied the molecular analysis of synchronous bilateral breast carcinoma and whether they are originating from a single or different clone. We examined 17 patients with breast carcinoma, including 12 patients with synchronous bilateral carcinomas and control group of 5 infiltrating ductal carcinomas with regional lymph node metastases. Mutations were quantitatively determined to detect loss of heterozygosity (LOH) and microsatellite size alterations for a broad panel of 15 markers, involving 10 chromosomes using polymerase chain reaction. The carcinomas were classified as de novo or metastasis based on three levels of concordance: (1) marker-affected tumors were considered concordant if 50% or more of the same markers were mutated, (2) same gene copy affected, and (3) temporal sequence of mutation acquisition. In synchronous bilateral breast carcinoma patients, molecular analysis showed discordant mutations in all cases, supporting the diagnosis of de novo bilateral primary breast carcinomas. In patients with lymph node metastases, the primary breast carcinoma and metastases shared the same mutations, revealing a metastatic lesion. In conclusion, the application of molecular technology may play an important role for the differential diagnosis of dual primary carcinomas vs a metastatic breast cancer to contralateral breast. In this study, synchronous bilateral breast cancers represent two independent primaries rather than metastatic events.

The diagnosis of malignancy in effusion cytology: a pattern recognition approach.

This review presents a pattern recognition approach for the diagnosis of malignant effusions. The cytomorphologic features of reactive mesothelial proliferation, mesothelioma and metastatic carcinoma are presented. In addition, the role of ancillary studies in challenging cases and the importance of integrating clinical findings are stressed. An algorithmic approach to the workup of serous effusions as well as pitfalls for false-positive diagnosis are discussed.

Critical diagnoses (critical values) in anatomic pathology.

Similar to critical values in clinical pathology, occasional diagnoses in surgical pathology and cytology may require urgent contact of the physician to facilitate rapid intervention or treatment. However, there are no established critical value (critical diagnosis) guidelines in anatomic pathology. As discussed herein, the Association of Directors of Anatomic and Surgical Pathology (ADASP) believes that establishing anatomic pathology critical diagnosis guidelines represents a practice improvement and patient safety initiative. The ADASP also recognizes that a generic anatomic pathology critical diagnosis guideline such as this should only be used as a template because the list needs to be customized at each individual hospital after consultation with relevant clinical services. Based on surveys of the membership of the ADASP, this document provides examples of possible critical diagnoses in anatomic pathology.

Critical values in cytology.

The concept of critical values (CVs) is well established in clinical pathology, and has only recently been suggested in surgical pathology. To evaluate CVs in cytology, we reviewed 2,000 cytology reports at two large academic medical centers. Cases considered CV included unexpected malignancy, disagreement between immediate interpretation and final diagnosis in fine-needle aspirations (FNAs), and evidence of microorganisms in non-gynecology (non-GYN) and FNA specimens. We identified 52 CV cases (2.6%), including 0.25% (1/400) GYN, 1.88% (15/800) non-GYN, and 4.5% (36/800) FNA. Most of these (42 cases) were unexpected malignancies. Documentation of physician notification was present in 30 out of 52 cases. We also did a survey with 22 cytopathologists and 13 clinicians at large academic medical centers. The participants were asked to rate 18 different possible CVs from 1 to 3 as follows: (1) no phone call necessary, (2) phone call within 24 hr, (3) phone call as soon as possible (ASAP). Participants could also list additional diagnoses they believed constituted a CV. Most respondents agreed on the need for a phone call ASAP in many situations, and important additional CV cases were suggested. We suggest that a consensus conference of leaders in anatomic pathology and clinicians might prove useful to propose guidelines for CVs in cytology.

Critical values in anatomic pathology.

Similar to critical values (CVs) in clinical pathology, occasional diagnoses in surgical pathology and cytology could require immediate notification of the physician to rapidly initiate treatment. However, there are no established CV guidelines in anatomic pathology. A retrospective review of surgical pathology reports was recently conducted to study the incidence of CVs in surgical pathology and to survey the perceptions of pathologists and clinicians about CVs in surgical pathology, with a similar analysis of CVs performed in cytology. The results indicated that CVs in surgical pathology and cytology are uncommon but not rare and that there is a wide range of opinion among pathologists and between pathologists and clinicians about the need for an immediate telephone call and about the degree of urgency. It was obvious from the study that there is a lack of consensus in identifying what constitutes surgical pathology and cytology CV cases. Since the Institute of Medicine's report on medical errors, there has been an increasing number of initiatives to improve patient safety. Having guidelines for anatomic pathology CVs could enhance patient safety, in contrast to the current practice in which CV cases are managed based on common sense and on personal experience. Therefore, a discussion involving the pathology community might prove useful in an attempt to establish anatomic pathology CV guidelines that could represent a practice improvement.

Solitary pulmonary metastasis presenting 20 years after primary resection of Wilms tumor.

Wilms tumor is the most common renal malignancy of childhood. Relapse occurs most often within 4 years of initial diagnosis, and the most common site of metastasis is the lung. We describe a 22-year-old man who presented with hemoptysis and a solitary pulmonary lesion 20 years after primary resection of Wilms tumor. Computed tomography of the chest showed an indeterminate pulmonary mass of heterogeneous attenuation with no other intrathoracic abnormalities. Surgical resection revealed a solitary pulmonary metastasis from Wilms tumor. Further evaluation yielded no evidence of extrathoracic metastases. This case shows that late relapse in the form of a solitary pulmonary mass can occur in patients with Wilms tumor.

Critical values in surgical pathology.

Analogous to critical values (CVs) in clinical pathology, occasional diagnoses in surgical pathology could require immediate contact of the physician to rapidly initiate treatment. However, there are no established CV guidelines in surgical pathology. We studied the incidence of CVs in surgical pathology by retrospective review of 2,659 surgical pathology reports and surveyed the perceptions of 5 clinicians and 11 pathologists about CVs in surgical pathology. We identified 13 CV cases (0.49%); 4 of the 13 reports documented phone calls to the clinician (most at least 1 day before final sign-out), and in 2 other reports the requisition included clinical history that implied previous knowledge of the diagnosis. The survey results indicated that for most diagnoses there was a range of opinions about whether immediate treatment was necessary and the need for a stat phone call. CVs occur in surgical pathology, but often there is no documented phone call in the surgical pathology report. Because there is little agreement about which diagnoses require a phone call and the degree of urgency, a consensus conference might prove useful for establishing surgical pathology CV guidelines and could represent a practice improvement.