Person:

Mark, Eugene

Background: Pulmonary capillary hemangiomatosis (PCH) is a rare disease, especially in infancy. Four infants have been reported up to the age of 12 months. So far, no familial patients are observed at this age. Patients: We report three siblings, two female newborns and a foetus of 15-week gestation of unrelated, healthy parents suffering from histologically proven PCH. The first girl presented with increased O2 requirements shortly after birth and patent ductus arteriosus (PDA). She subsequently developed progressive respiratory failure and pulmonary hypertension and died at the age of five months. The second girl presented with clinical signs of bronchial obstruction at the age of three months. The work-up showed a PDA—which was surgically closed—pulmonary hypertension, and bronchial wall instability with stenosis of the left main bronchus. Transient oxygen therapy was required with viral infections. The girl is now six years old and clinically stable without additional O2 requirements. Failure to thrive during infancy and a somewhat delayed development may be the consequence of the disease itself but also could be attributed to repeated episodes of respiratory failure and a long-term systemic steroid therapy. The third pregnancy ended as spontaneous abortion. The foetus showed histological signs of PCH. Conclusion: Despite the differences in clinical course, the trias of PCH, PDA, and pulmonary hypertension in the two life born girls suggests a genetic background.

Background:: One of the goals for a Whole Slide Imaging (WSI) system is implementation in the clinical practice of pathology. One of the unresolved problems in accomplishing this goal is the speed of the entire process, i.e., from viewing the slides through making the final diagnosis. Most users are not satisfied with the correct viewing speeds of available systems. We have evaluated a new WSI viewing station and tool that focuses on speed. Method: A prototype WSI viewer based on PlayStation®3 with wireless controllers was evaluated at the Department of Pathology at MGH for the following reasons: 1. For the simulation of signing-out cases; 2. Enabling discussion at a consensus conference; and 3. Use at slide seminars during a Continuing Medical Education course. Results:: Pathologists were being able to use the system comfortably after 0–15 min training. There were no complaints regarding speed. Most pathologists were satisfied with the functionality, usability and speed of the system. The most difficult situation was simulating diagnostic sign-out. Conclusion:: The preliminary results of adapting the Sony PlayStation®3 (PS3®) as an ultra-high speed WSI viewing system were promising. The achieved speed is consistent with what would be needed to use WSI in daily practice.

Context.—Whole-slide imaging technology offers promise for rapid, Internet-based telepathology consultations between institutions. Before implementation, technical issues, pathologist adaptability, and morphologic pitfalls must be well characterized. Objective.—To determine whether interpretation of whole-slide images differed from glass-slide interpretation in difficult surgical pathology cases. Design.—Diagnostically challenging pathology slides from a variety of anatomic sites from an outside laboratory were scanned into whole digital format. Digital and glass slides were independently diagnosed by 2 subspecialty pathologists. Reference, digital, and glass-slide interpretations were compared. Operator comments on technical issues were gathered. Results.—Fifty-three case pairs were analyzed. There was agreement among digital, glass, and reference diagnoses in 45 cases (85%) and between digital and glass diagnoses in 48 (91%) cases. There were 5 digital cases (9%) discordant with both reference and glass diagnoses. Further review of each of these cases indicated an incorrect digital whole-slide interpretation. Neoplastic cases showed better correlation (93%) than did cases of nonneoplastic disease (88%). Comments on discordant cases related to digital whole technology focused on issues such as fine resolution and navigating ability at high magnification. Conclusions.—Overall concordance between digital whole-slide and standard glass-slide interpretations was good at 91%. Adjustments in technology, case selection, and technology familiarization should improve performance, making digital whole-slide review feasible for broader telepathology subspecialty consultation applications.

While squamous cell carcinoma (SCC) is the most common tracheal malignancy, few reports describe the pathologic considerations that may guide intraoperative decisions and prognostic assessment. We reviewed 59 tracheal SCC treated between 1985 and 2008 by segmental resection of the trachea, including resection of the carina in 24% and inferior larynx in 14%. We classified these tumors by grading histologic differentiation and microscopic features used in SCC of other sites. Of 59 tumors, 24% (14 of 59) were well differentiated, 49% (29 of 59) were moderately differentiated, and 27% (16 of 59) were poorly differentiated. Unfavorable prognostic factors were tumor extension into the thyroid gland (all of five so-afflicted patients died of tumor progression within 3 years) and lymphatic invasion (mean survival 4.6 versus 7.6 years). Keratinization, dyskeratosis, acantholysis, necrosis, and tumor thickness did not predict prognosis. As surgical resection is the only curative treatment; the surgeon should establish clean lines of resection using, as appropriate, intraoperative frozen section. The pathologist can provide additional important prognostic information, including tumor differentiation and extent, invasion of surgical margins, and extension into the thyroid.

Purpose Approximately 5% of lung adenocarcinomas harbor an EML4-ALK gene fusion and define a unique tumor group that may be responsive to targeted therapy. However ALK-rearranged lung adenocarcinomas are difficult to detect by either standard fluorescence in-situ hybridization (FISH) or immunohistochemical (IHC) assays. In the present study we used novel antibodies to compare ALK protein expression in genetically defined lung cancers and anaplastic large cell lymphomas (ALCL).

Experimental Design We analyzed 174 tumors with one standard, and two novel monoclonal antibodies recognizing the ALK protein. Immunostained tissue sections were assessed for the level of tumor-specific ALK expression by objective quantitative image analysis and independently by three pathologists.

Results ALK protein is invariably and exclusively expressed in ALK-rearranged lung adenocarcinomas but at much lower levels than in the prototypic ALK-rearranged tumor, anaplastic large cell lymphoma, and as a result, often not detected by conventional IHC. We further validate a novel IHC that shows excellent sensitivity and specificity (100% and 99%, respectively) for the detection of ALK-rearranged lung adenocarcinomas in biopsy specimens with excellent interobserver agreement between pathologists (kappa statistic, 0.94).

Conclusions Low levels of ALK protein expression is a characteristic feature of ALK-rearranged lung adenocarcinomas. However a novel, highly sensitive IHC assay reliably detects lung adenocarcinomas with ALK rearrangements and obviates the need for FISH analysis for the majority of cases and therefore could be routinely applicable in clinical practice to detect lung cancers that may be responsive to ALK inhibitors.

Purpose The anaplastic large cell kinase gene (ALK) is rearranged in approximately 5% of lung adenocarcinomas within the Asian population. We evaluated the incidence and the characteristics of ALK-rearranged lung adenocarcinomas within the Western population and the optimal diagnostic modality to detect ALK rearrangements in routine clinical practice.

Experimental Design We tested 358 lung adenocarcinomas from three institutions for ALK rearrangements by fluorescent in-situ hybridization (FISH) and immunohistochemistry (IHC) with and without tyramide amplification (TA). The clinicopathologic characteristics of tumors with and without ALK rearrangements were compared.

Results We identified 20 lung adenocarcinomas (5.6%) with ALK rearrangements within our cohort of Western patients. ALK rearrangement was associated with younger age (P = 0.0002), never smoking (P < 0.0001), advanced clinical stage (P = 0.0001), and a solid histology with signet-ring cells (P < 0.0001). ALK rearrangement was identified by FISH in 95% of cases, IHC with and without TA in 80% and 40% of cases, respectively, but neither FISH nor IHC alone detected all cases with ALK rearrangement on initial screening. None of the ALK-rearranged tumors harbored coexisting EGFR mutations.

Conclusions Lung adenocarcinomas with ALK rearrangements are uncommon in the Western population and represent a distinct entity of carcinomas with unique characteristics. For suspected cases dual diagnostic testing, with FISH and IHC, should be considered to accurately identify lung adenocarcinomas with ALK rearrangement.