Telma C. Pereira

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.

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.

Rectal Pulse Granuloma

Pulse granuloma is a rare benign entity, most likely representing a foreign body reaction to vegetable particles. We report a case of a pulse granuloma involving the rectum. The patient presented with a submucosal and intramuscular mass lesion found at routine rectal examination and subsequent colonoscopy. The mass was excised and the microscopic examination revealed acute and chronic inflammatory cells, foreign-body giant cells, vegetable matter, and convoluted hyaline rings and scattered circular structures containing basophilic granules, consistent with pulse granuloma. There are a few reports in the literature of pulse granulomas, with most occurring in the oral cavity or lungs. To the best of our knowledge, this is the first reported example of pulse granuloma in the rectum. Although rare, familiarity with this entitys distinctive histopathologic features may avoid a delay in diagnosis and prevent the expense of distinguishing it from its histologic lookalikes.

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.

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.

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 Medicines 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.

Pathologic quiz case : Elderly man with bright red blood per rectum

71-year-old white man with no prior history of malignancy and a 2-week history of obstipation, increasing abdominal girth, and abdominal cramping sought medical attention after he began passing bright red blood per rectum. He underwent colonoscopy, which revealed a fungating and hemorrhagic rectosigmoid mass lesion. Shortly after colonoscopy, the patient experienced a rapid decrease in oxygen saturation and required intubation with mechanical respiration. During the next several days, he developed acute renal failure leading to multiple organ system failure and eventually death. Before he died, the patient was sent for computed tomographic scans of the chest, abdomen, and pelvis, which revealed extensive ‘‘metastatic disease’’ involving the lungs, liver, and multiple bony sites. While in radiology, a computed tomographic scan‐guided needle biopsy of a tumor nodule in the bony pelvis was conducted. The needle aspiration slides were relatively hypocellular and contained a mixture of discohesive cells. Some of these cells displayed overt cytologic features of malignancy, including large irregular nuclei and prominent eosinophilic nucleoli (Figure 1). Osteoclast-type giant cells were admixed with the malignant cells. The core biopsy demonstrated a sheetlike expanse of the same malignant cells, some of which possessed long, tapering cytoplasm. A smattering