Processing the entire capsule in thyroid follicular lesions improves diagnostic accuracy.

BACKGROUND: There is contradictory evidence in literature with respect to diagnosis and management of follicular lesions of the thyroid gland. From surgical pathology stand point, pathologists require submission and processing of entire capsule for microscopic evaluation. This can be extremely challenging especially in larger lesions. METHOD: We studied the impact of submitting entire capsule on final pathologic diagnosis in cases on which only representative sections were submitted initially and entire capsule was submitted subsequently. RESULTS: A total of 80 specimens were identified. Mean size of the nodule in these cases was 4.4 ±â€¯1.9 cm. Mean initial tissue sections submitted were 11.6 ±â€¯3.6. Entire capsule was submitted subsequently in an additional 12.6 ±â€¯13.3 sections. Submission of entire capsule contributed to final diagnosis in 3 (3.8%) cases whereby foci of capsular microinvasion were identified. There was no significant difference in the requirement of subsequent sections in specimens grossed by residents compared to those grossed by pathologist assistants (10.4 ±â€¯10.8 vs. 14.4 ±â€¯14.9, p = 0.18). The processing cost of additional sections of capsule was $ 4143 in these cases. CONCLUSION: Processing of entire capsule in thyroid follicular lesions has a definitive yield that comes at a high cost. Thin slicing and looking for areas of gross abnormality such as mushrooming may be more practical especially in larger lesions.

Incidence of Extraprostatic Extension at Radical Prostatectomy with Pure Gleason Score 3 + 3 = 6 (Grade Group 1) Cancer: Implications for Whether Gleason Score 6 Prostate Cancer Should be Renamed "Not Cancer" and for Selection Criteria for Active Surveillance.

PURPOSE: We assessed the risk of locally aggressive behavior in pure Gleason score 6 (Grade Group 1) prostate cancer using contemporary grading criteria. To our knowledge this has been studied in only 1 prior cohort. MATERIALS AND METHODS: We evaluated consecutive radical prostatectomy specimens from an academic institution, including those from 3,291 men with Gleason score 6 and 4,202 with Gleason score 3 + 4 = 7 (Grade Group 2) disease between 2005 and 2016. For dichotomous variables the Pearson chi-square test was used. RESULTS: Of the 3,288 Gleason score 6 cancer cases 128 (3.9%) showed focal extraprostatic extension compared to 593 of the 4,202 (14.1%) with Gleason score 3 + 4 = 7 (p <0.0001). Of the 3,288 Gleason score 6 cancer cases 79 (2.4%) showed nonfocal extraprostatic extension compared to 639 of the 4,202 (15.2%) with Gleason score 3 + 4 = 7 (p <0.0001). The incidence of focal extraprostatic extension with Gleason score 3 + 4 = 7 with less than 5% Gleason pattern 4 was 129 of 1,147 cases (11.2%), which was between Gleason scores 6 and 3 + 4 = 7 with greater than 5% Gleason pattern 4. The incidence of nonfocal extraprostatic extension in Gleason score 3 + 4 = 7 with less than 5% Gleason pattern 4 was 96 of 1,147 cases (8.4%), which was between Gleason scores 6 and 3 + 4 = 7 with greater than 5% Gleason pattern 4. One of the 3,290 Gleason score 6 cases (0.03%) showed seminal vesicle invasion compared to 93 of the 4,202 (2.2%) of Gleason score 3 + 4 = 7 (p <0.0001). A limitation of our study was its retrospective design. CONCLUSIONS: It is not rare for pure Gleason score 6 prostate cancer to locally extend out of the prostate 3.9% focally and 2.4% nonfocally. In extremely rare cases Gleason score 6 can be associated with seminal vesicle invasion and yet not lymph node metastases. Our overall findings support the argument for continuing to use the term cancer for these tumors.

Atypical glandular cells (AGC): Cytology of glandular lesions of the uterine cervix.

The Pap smear is a well-known screening tool for squamous lesions of the uterine cervix. However, its screening role in glandular lesions is less effective. The incidence of squamous cell carcinoma of the cervix has dramatically decreased with the advent of Pap smear and recent understanding related to HPV carcinogenesis of cervical cancers including the advent of HPV vaccines. However, in recent years, the incidence of glandular abnormalities, diagnosed on Pap smears, has increased with greater sensitivity and precision. The incidence of atypical glandular cells (AGC) is approximately 0.18-0.74% of all cervical smears with a reported prevalence of 2.5% among all Pap smears. A high degree of suspicion, good clinical history, and the presence of diagnostic cytomorphological findings are essential for the proper interpretation of glandular cell abnormalities. A methodical approach to evaluate Pap smear greatly helps interpretation and avoids the diagnostic pitfalls. The Bethesda System for reporting cervical cytology has categorized glandular cell abnormalities into various categories as follows: Endocervical adenocarcinoma in situ (AIS)Atypical glandular cells (AGCs) Endocervical cells: a1 NOS or specify in comments; a2 Favor neoplasticEndometrial cells: NOS or specify in comments Adenocarcinoma (AdCa) EndocervicalEndometrialExtrauterineNOS Subtle differences in quantitative and qualitative cytologic features are essential for distinguishing one category from another. In this chapter, we highlight an organized approach for the interpretation of glandular abnormalities in Pap smear for our readers. This is an overview of the Bethesda categories, the reason for classification, and differential diagnosis with key characteristic features. An approach to the methodical evaluation of hyperchromatic crowded groups is discussed with key cytomorphologic differences. An algorithmic approach is suggested to facilitate the interpretation of various AGC categories.

Cell-blocks and hematolymphoid lesions.

Cell-blocks are an important component for evaluation for hematolymphoid lesions. They are especially critical for immunocharacterization of the lymphoid population especially when flow cytometry is not available or cannot be performed. In addition, cell-blocks allow various molecular pathology tests including gene rearrangement studies and FISH, proteomics analysis, and microbiology/histochemical special stains. Fine-needle aspiration (FNA) for mass lesions, lymphadenopathy, and effusion fluids are common cytopathology specimens which are frequently cell-blocked. The differential diagnosis of enlarged lymph nodes (LNs) and mass lesions is broad and includes reactive processes, granulomatous lesions and malignancies including solid tumor metastases and various types of hematological malignancies, of which lymphoma would be most common. Depending on the patient population, most lymphomas may be diagnosed with immunocharacterization on cell-block or/and flow cytometry in concert with excellent cytomorphology in Diff-Quik stained FNA aspirate smears. However, a proportion of lymphoma cases (up to 12-30%) may still require an excisional LN biopsy to evaluate architectural parameters. Similarly, various effusion fluids suspicious for lymphoma can be immunocharacterized by immunostaining of cell-block sections (or/and by flow cytometry). Availability of quantitatively and qualitatively optimum cell-blocks of specimens to be evaluated for hematolymphoid processes is critical for immunohistochemistry, polymerase chain reaction, in situ hybridization (FISH), and gene expression profiling studies.

Squamous intraepithelial lesions (SIL: LSIL, HSIL, ASCUS, ASC-H, LSIL-H) of Uterine Cervix and Bethesda System.

For every 100,000 women in the United States, eight new cervical cancer cases and two deaths are reported as per the most recent (2017) Center of Disease Control and Prevention statistics. Of all the gynecologic cancers (ovary, uterus, cervix, vagina, and vulva), only cervical cancer has a screening test. Cervical Pap test (or Pap smear) is the best screening method for cervical precancerous lesions and is best reported using a unified and a well-established reporting system like The Bethesda System. In this system, "Epithelial cell abnormality: Squamous" includes squamous intraepithelial lesion (SIL) category which encompasses a spectrum of squamous cell lesions starting from the precancerous lesions of low-grade SIL (LSIL) to high-grade SIL (HSIL), and ultimately invasive squamous cell carcinoma. However, depending on the qualitative and quantitative limitations with the specimen, some equivocal morphological features suggestive of squamous cell abnormality may fall under equivocal category: "Atypical Squamous Cells" (ASCs), which are subdivided into two categories; "Atypical Squamous Cells of Undetermined Significance" (ASC-US) or "Atypical Squamous Cells, HSIL cannot be excluded" (ASC-H), based on the suspected underlying lesion LSIL versus HSIL, respectively. This review provides the key cytologic features that distinguish Bethesda squamous categories from other important entities, using algorithmic approach and illustrations of common cytomorphologic patterns for clear identification of those entities in practice. The important mimickers which may be considered during the differential interpretation of SIL are discussed and presented here in a brief cytomorphologic review.

Metastatic Testicular Choriocarcinoma: An Unusual Cause of Upper Gastrointestinal Bleed.

Testicular cancer is the most common neoplasia in men between the ages of 15 to 44 years. Choriocarcinoma represents less than 2% of testicular tumors. It is usually characterized by an early hematogenous spread to the lungs and brain. Metastases to the gastrointestinal (GI) tract are extremely rare. Most metastatic lesions in the GI tract are seen in the small bowel. We present a 30-year-old African American male with a past medical history significant for stage III non-seminomatous germ cell testicular cancer. The patient was initially started on chemotherapy; however, he was not compliant with his treatment. One year following his diagnosis, he presented to the hospital with shortness of breath and chest pain. CT angiography of the chest was done and showed multiple masses scattered in all lung fields. The lesions were believed to be metastatic in nature. Laboratory testing showed a human chorionic gonadotropin beta level of 40,453 IU/L, LDH 258 IUnits/L, and alfa-fetoprotein 8.9 ng/mL. His hospital stay was complicated with melena and a drop in his hemoglobin from a baseline of 12 to 7 gm/dL. An esophagogastroduodenoscopy (EGD) showed three erythematous friable nodules in the gastric body. Biopsy results came back consistent with metastatic choriocarcinoma. The patient was offered salvage chemotherapy; however, he refused treatment and elected to proceed with suppurative measures. Testicular choriocarcinomas are the most aggressive and rapidly arising germ cell tumors. By the time they are diagnosed, large subsets of cases have already metastasized. Patients usually present with symptoms of hemorrhage in metastatic sites due to the high level of vascularization of those lesions. Gastrointestinal metastases from choriocarcinomas are very rare which account for 5% of all metastatic lesions with around 1% affecting the stomach. The presenting symptoms of stomach metastases are melena and/or hematemesis along with anemia. Although extremely rare, gastric metastases of choriocarcinoma should be kept in mind as part of the differential diagnosis for young patients with upper GI bleeding.

Factors affecting the concordance of radiologic and pathologic tumor size in breast carcinoma.

BACKGROUND: Radiologic assessment of tumor size is an integral part of the work-up for breast carcinoma. With improved radiologic equipment, surgical decision relies profoundly upon radiologic/clinical stage. We wanted to see the concordance between radiologic and pathologic tumor size to infer how accurate radiologic/clinical staging is. MATERIALS AND METHODS: The surgical pathology and ultrasonography reports of patients with breast carcinoma were reviewed. Data were collected for 406 cases. Concordance was defined as a size difference within ±2 mm. RESULTS: The difference between radiologic and pathologic tumor size was within ±2 mm in 40.4% cases. The mean radiologic size was 1.73 ± 1.06 cm. The mean pathologic size was 1.84 ± 1.24 cm. A paired t-test showed a significant mean difference between radiologic and pathologic measurements (0.12 ± 1.03 cm, p = 0.03). Despite the size difference, stage classification was the same in 59.9% of cases. Radiologic size overestimated stage in 14.5% of cases and underestimated stage in 25.6% of cases. The concordance rate was significantly higher for tumors ≤2 cm (pT1) (51.1%) as compared to those greater than 2 cm (≥pT2) (19.7%) (p < 0.0001). Significantly more lumpectomy specimens (47.5%) had concordance when compared to mastectomy specimens (29.8%) (p < 0.0001). Invasive ductal carcinoma had better concordance compared to other tumors (p = 0.02). CONCLUSION: Mean pathologic tumor size was significantly different from mean radiologic tumor size. Concordance was in just over 40% of cases and the stage classification was the same in about 60% of cases only. Therefore, surgical decision of lumpectomy versus mastectomy based on radiologic tumor size may not always be accurate.

Utility of Additional Tissue Sections in Surgical Pathology.

BACKGROUND: To avoid diagnostic errors such as missed diagnosis and errors in staging tumors due to inadequate tissue sampling, pathologists submit additional sections (AS). OBJECTIVE: This study assessed frequency, diagnostic yield, distribution, and cost of AS. METHOD: Among 1542 AS cases, we calculated mean AS per case; fraction of AS that altered diagnosis or stage; AS variation by tissue, malignant versus benign lesions, presence or absence of neoadjuvant therapy, mass, margin, lymph nodes, or other source, resident versus pathologist assistant (PA) dissector; and AS cost per case. RESULTS: Overall 9.2 ± 8.8 AS were collected per case. In only 3.8% (58/1542) of cases AS altered diagnosis or stage. Urinary bladder cases provoked the most AS: 19.5 ± 15.1 per case. Significantly more AS came from malignant versus benign lesions (10.8 ± 9.7 vs 7.6 ± 7.5, P = <.0001) and from specimens treated with neoadjuvant therapy versus malignant lesions not so treated (12.3 ± 9.4 vs 10.3 ± 9.8, P = .02). Lymph nodes were sampled more heavily compared with mass, margin, and other sites combined (11.8 ± 11.4 vs 8.9 ± 8.4, P = .003), but in 78.4% (1209/1542) of cases, AS were from mass. Of diagnosis or stage altering AS cases, two thirds (38/58) were from masses, one fifth (11/58) from lymph nodes, a 10th (6/58) from margins, and a 20th (3/58) from other specimen sites. Resident versus pathologist assistant dissection caused no significant AS difference. AS contributed 40% cost per case. CONCLUSIONS: AS per case ranged widely; their diagnostic yield was low; they were highest in urinary bladder specimens, in malignant and particularly neoadjuvant-treated lesions. Although lymph nodes were most heavily sampled, most AS were from masses. Resident dissection did not increase AS and cost of AS was high.

Role of "Second Look" Lymph Node Search in Harvesting Optimal Number of Lymph Nodes for Staging of Colorectal Carcinoma.

As with other malignancies, lymph node metastasis is an important staging element and prognostic factor in colorectal carcinomas. The number of involved lymph nodes is directly related to decreased 5-year overall survival for all pT stages according to United States Surveillance, Epidemiology, and End Results (SEER) cancer registry database. The National Quality Forum specifies that the presence of at least 12 lymph nodes in a surgical resection is one of the key quality measures for the evaluation of colorectal cancer. Therefore, the harvesting of a minimum of twelve lymph nodes is the most widely accepted standard for evaluating colorectal cancer. Since this is an accepted quality standard, a second attempt at lymph node dissection in the gross specimen is often performed when the initial lymph node count is less than 12, incurring a delay in reporting and additional expense. However, this is an arbitrary number and not based on any hard scientific evidence. We decided to investigate whether the additional effort and expense of submitting additional lymph nodes had any effect on pathologic lymph node staging (pN). We identified a total of 99 colectomies for colorectal cancer in which the prosector subsequently submitted additional lymph nodes following initial review. The mean lymph node count increased from 8.3 ± 7.5 on initial search to 14.6 ± 8.0 following submission of additional sections. The number of cases meeting the target of 12 lymph nodes increased from 14 to 69. Examination of the additional lymph nodes resulted in pathologic upstaging (pN) of five cases. Gross reexamination and submission of additional lymph nodes may provide more accurate staging in a limited number of cases. Whether exhaustive submission of mesenteric fat or fat-clearing methods is justified will need to be further investigated.

Tumor Size in Breast Carcinoma: Gross Measurement Is Important!

INTRODUCTION: The staging of breast carcinoma is mainly dependent on tumor size and lymph node status. Small increments in tumor size upstage the patient. An accurate determination of the tumor size is therefore critically important. Although the final staging is based on microscopic size, pathologists rely on gross measurements in a considerable number of cases. METHODS: We investigated the concordance between gross and microscopic measurements of breast carcinoma as well as factors affecting this concordance. This study is a retrospective review of surgical pathology reports of invasive breast carcinomas. Data were collected for 411 cases. Concordance was defined as a size difference within ±2 mm. RESULTS: Gross and microscopic sizes were identical in 33.1% of cases. Gross and microscopic size difference was within ±2 mm in 56% of cases. Despite the size difference, stage classification ended up being the same in 68.6% of cases. Tumor stage was over estimated by gross measurement in 17.0% of cases and underestimated in 14.4% of cases. The concordance was significantly higher for those tumors in which final pathologic tumor (pT) size was greater than 2 cm (≥pT2) as compared with those less than or equal to 2 cm (≤pT1; P < .0001). A higher proportion of mastectomy specimens (61.4%) were concordant as compared with lumpectomy specimens (52.1%). CONCLUSION: Gross and microscopic tumor sizes were concordant in 56% of cases. Stage classification based on gross and microscopic tumor size was different in nearly one third (31.4%) of cases. Gross tumor size is critically important in accurate staging at least in cases where tumor size cannot be confirmed microscopically.

Autoimmune Hepatitis: A Risk Factor for Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a very aggressive and lethal tumor, which arises from the epithelial cells of bile ducts. CCA comprises about 3% of all gastrointestinal malignancies and its incidence is on the rise in the recent years. Anatomically, it is classified into intrahepatic, perihilar, or extrahepatic (distal) CCA. There are a number of risk factors associated with CCA including primary sclerosing cholangitis, fibropolycystic liver disease, parasitic infection, viral hepatitis, chronic liver disease, and genetic disorders like Lynch syndrome. Autoimmune hepatitis is also recently reported to have an association with development of CCA. We report an interesting case of perihilar CCA in the setting of autoimmune hepatitis along with a literature review. This case highlights the importance of early treatment and close clinical follow-up of patients with autoimmune hepatitis for development of CCA.

Cisplatin-Induced Nephrotoxicity and HIV Associated Nephropathy: Mimickers of Myeloma-Like Cast Nephropathy.

Myeloma cast nephropathy is an obstructing disorder of renal tubules, caused by precipitation of Bence Jones proteins. Myeloma-like cast nephropathy (MLCN) has been reported in the literature to occur in various primary renal and nonrenal diseases. We present a series of three rare cases of cast nephropathy, two of which are HIV patients, and the third patient is receiving cisplatin-based chemotherapy. However, in all three patients plasma cell dyscrasia has been ruled out. A 30-year-old male was admitted to the hospital with facial cellulitis. The second patient is a 31-year-old male who presented with Pneumocystis jiroveci pneumonia. The third patient was treated with cisplatin-based chemotherapy for carcinoma. First two cases revealed foci of diffuse tubular dilatation containing hyaline casts and interstitial inflammatory infiltrate, in addition to globally sclerotic glomeruli with ultrastructural foot process fusion and mesangium expansion. The third case showed acute tubular injury and cast formation of irregular casts composed of amorphous or granular material of low density admixed with scattered high electron-dense globules. Myeloma-like cast nephropathy and true myeloma cast nephropathy pose similar destructive effects on renal parenchyma. This new pattern of HIV-related nephropathy should be considered in HIV patients with MLCN, once monoclonal gammopathy is ruled out.

Pulmonary placental transmogrification associated with adenocarcinoma of the lung: a case report with a comprehensive review of the literature.

Pulmonary placental transmogrification (PT) is a rare entity with less than 40 cases reported in the literature. Most reported cases are associated with either bullous emphysema or with pulmonary fibrochondromatous hamartomas. We present only the second case of PT associated with adenocarcinoma of the lung. A 67-year-old female with multiple chronic medical ailments presented with shortness of breath and was found to have a 6-cm mass in the upper lobe of her right lung. A computed tomography (CT) guided core biopsy was performed that showed a well-differentiated adenocarcinoma. Interestingly the normal lung tissue showed placental villous architecture. A unique feature of our case is that the diagnosis was made on a needle core biopsy, unlike all the other cases in the literature. We also provide a comprehensive review of this rare entity.

Pulmonary placental transmogrification associated with adenocarcinoma of the lung: a case report with a comprehensive review of the literature

Pulmonary placental transmogrification (PT) is a rare entity with less than 40 cases reported in the literature. Most reported cases are associated with either bullous emphysema or with pulmonary fibrochondromatous hamartomas. We present only the second case of PT associated with adenocarcinoma of the lung. A 67-year-old female with multiple chronic medical ailments presented with shortness of breath and was found to have a 6-cm mass in the upper lobe of her right lung. A computed tomography (CT) guided core biopsy was performed that showed a well-differentiated adenocarcinoma. Interestingly the normal lung tissue showed placental villous architecture. A unique feature of our case is that the diagnosis was made on a needle core biopsy, unlike all the other cases in the literature. We also provide a comprehensive review of this rare entity.