Actinomyces ductular dacryoadenitis resulting in a lacrimal gland abscess.

Lacrimal gland ductulitis is a rare infection of the lacrimal gland ductules. Individuals affected report a history of chronic mucopurulent conjunctivitis with "stringy" discharge. All patients are clinically noted to have an inflamed lacrimal gland ductule. Prior reports have suggested Actinomyces species as the "probable" etiology.We report the findings of a 42-year-old male found to have lacrimal gland ductulitis with a lacrimal gland abscess, confirmed by radiologic studies. Surgical drainage was necessitated and performed. Histopathologic analysis confirmed colonization by Actinomyces species, as well as the presence of sulfur granules. To our knowledge, this is the first report of Actinomyces lacrimal gland ductulitis resulting in a secondary lacrimal gland abscess.

Applying the Paris system for reporting urine cytology to challenging cytology cases.

BACKGROUND: Implementing the Paris system for reporting urine cytology (TPS) can substantiate atypical diagnosis while improving standardization and risk stratification. This study evaluates its performance and reproducibility in challenging cases and examines whether focused education of morphological features can improve outcomes. METHODS: In our prior study, urine cytology cases diagnosed as "atypical" with surgical follow-up were used. Cases showing poor agreement in that study were collected for this one. Representative photographs of each case were taken and distributed via online questionnaires. Participants were asked to render an initial diagnosis and evaluate the presence of several morphological features. Educational material was distributed, followed by additional questionnaires. RESULTS: Three participants evaluated 40 cases before and after educational materials. TPS diagnoses were significantly more specific (0.23 vs 0.59, P = 0.004) and more accurate (0.43 vs 0.66, P = 0.0125) than diagnoses made with our institutional system. Fewer overall cases were diagnosed as "atypical" with TPS. TPS education resulted in slightly, though not significantly, more specific diagnoses (0.25 vs 0.59, P = 0.083). Interobserver agreement decreased for nuclear-to-cytoplasmic (N/C) ratio, TPS diagnoses and initial diagnoses, and increased for all other features. TPS resulted in downgrading of cases with biopsy-proven low grade urothelial neoplasm (LGUN) from "atypical" to negative for high grade urothelial carcinoma (NHGUC) (P = 0.018). CONCLUSIONS: Use of TPS in challenging urine cytology cases can improve specificity, risk stratification, and diagnostic accuracy while decreasing the number of "atypical" diagnoses. Though training can help cytopathologists better apply these criteria, it is unclear how to effectively improve evaluation of N/C ratio.

Diagnosis of Lymphoma Using Fine-Needle Aspiration Biopsy and Core-Needle Biopsy: A Single-Institution Experience.

OBJECTIVE: The objective is to study the efficacy of fine-needle aspiration biopsy (FNAB) and core-needle biopsy (CNB) in the diagnosis of lymphoma in a single institution. STUDY DESIGN: We retrospectively reviewed 635 FNAB/CNB cases performed in our institution to rule out lymphoma during a 4-year period and collected the relevant clinical and pathological information for statistical analysis. RESULTS AND CONCLUSIONS: This cohort comprised 275 males and 360 females, with a median age of 57 years. Among the 593 cases with adequate diagnostic materials for lymphoma work-up, 226 were positive for lymphoma, 286 were negative for lymphoma, and 81 were nondiagnostic. Each case had an FNAB, and 191 cases also underwent a CNB. The subclassification rate according to the WHO (2008) was 67% overall, 81% for the FNAB with CNB group, and 40% for the FNAB group. In the FNAB with CNB group, the subclassification rates for cases with and without a history of lymphoma were not significantly different. A definitive diagnosis of lymphoma relied on ancillary studies, but was not affected by location, or the needle gauge of CNB. Follow-up data revealed a high diagnostic accuracy of FNAB with CNB. In conclusion, the use of FNAB and CNB with ancillary studies is effective in providing a definitive diagnosis of lymphoma in our experience at the Northwell Health System.

Amyloidoma of Stomach: A Case Report.

OBJECTIVE: Amyloidomas are tumor-like deposits of amyloid. Amyloidoma of the gastrointestinal tract is rare. To the best of our knowledge, this is the first instance of diagnosis of an amyloidoma in the gastrointestinal tract by fine needle aspiration (FNA). STUDY DESIGN: We report a case of a 64-year-old male with a history of ulcerative colitis and primary sclerosing cholangitis who was incidentally found to have a mass in the stomach wall. RESULTS: Initially thought to be gastrointestinal stromal tumor, FNA demonstrated the lesion to be amyloidoma with a prominent giant cell reaction. This was further confirmed by mass spectrometry. This is the only case report of diagnosis of a gastric amyloidoma by FNA. CONCLUSION: The presence of a florid giant cell reaction in the absence of ulceration or an inflammatory or neoplastic lesion should alert the pathologist to the possibility of an amyloidoma. This is the only case report of diagnosis of a gastric amyloidoma by FNA.

Analysis of the Cytomorphological Features in Atypical Urine Specimens following Application of The Paris System for Reporting Urinary Cytology.

BACKGROUND: This study investigates the use of The Paris System (TPS) for Reporting Urinary Cytopathology and examines the performance of individual and combined morphological features in atypical urine cytologies. METHODS: We reviewed 118 atypical cytologies with subsequent bladder biopsies for the presence of several morphological features and reclassified them into Paris System categories. The sensitivity and specificity of individual and combined features were calculated along with the risk of malignancy. RESULTS: An elevated nuclear-to-cytoplasmic ratio was only predictive of malignancy if seen in single cells, while irregular nuclear borders, hyperchromasia, and coarse granular chromatin were predictive in single cells and in groups. Identification of coarse chromatin alone yielded a malignancy risk comparable to 2-feature combinations. The use of TPS criteria identified the specimens at a higher risk of malignancy. CONCLUSION: Our findings support the use of TPS criteria, suggesting that the presence of coarse chromatin is more specific than other individual features, and confirming that cytologic atypia is more worrisome in single cells than in groups.

Mechanisms of progression of ductal carcinoma in situ of the breast to invasive cancer. A hypothesis.

Ductal carcinoma in situ (DCIS), a known precursor lesion of invasive cancer of the female breast, is surrounded by a thick basement membrane and a layer of myoepithelial cells. For DCIS to become invasive, both these barriers must be breached by cancer cells. It has been repeatedly suggested that proteolytic enzymes are somehow involved in this process but a direct proof of this event has never been provided. It is our hypothesis that invasion of the DCIS by capillary vessels derived from the periductal necklace of vessels is the most likely mechanism of breaching the basement membrane, providing an escape hatch for cancer cells. This hypothesis was initially tested on ten randomly selected cases of DCIS, with or without invasion. Capillary vessels were visualized by staining histologic sections with an antibody to CD 34 and, in three cases, by combined stain for CD 34 and collagen IV. In five of the 10 cases of DCIS, the presence of discrete capillary vessels invading DCIS could be documented. In two of these five cases, the vessels subdivided the cancerous ducts into territories of unequal sizes. Vascular invasion of DCIS is a plausible mechanism of breaching the basement membrane in DCIS as a prelude to invasion. This hypothesis must be further tested on a much larger number of cases. The hypothesis, if confirmed, may suggest that invasive cancer derived from DCIS may be prevented by antiangiogenic therapy.

Conjunctival Capillary Hemangioma.

Conjunctival hemangioma over the age of 60 is rare, with few cases reported in the literature. We present a unique case of a conjunctival capillary hemangioma, adding to the sparse literature of this uncommon vascular tumor. Here, we present an interesting case of spontaneous development of this tumor at age 68, without associated systemic disease process or cutaneous manifestations.

Utility of intraoperative frozen sections for thyroid nodules with prior fine needle aspiration cytology diagnosis.

INTRODUCTION: The objective of this study was to evaluate the role of intraoperative frozen section (IFS) in determining the course of surgery in thyroid nodules with a prior fine needle aspiration (FNA) biopsy diagnosis. In addition, reliability of FNA interpretation to guide surgical management without IFS was investigated. MATERIAL AND METHODS: This is a retrospective study of all patients who had a FNA biopsy, IFS, and final pathology performed on a thyroid nodule over a 9 month period. The extent of surgery at the time of the IFS was recorded. Subsequent change in surgical procedure following the IFS diagnosis was noted in each of the Bethesda diagnostic categories. RESULTS: 55% of the cases were deferred at IFS overall, with 68 and 86% in Bethesda III and IV categories, respectively. Overall, there was a change in management in 6% of cases. CONCLUSIONS: Our study does not support the use of IFS for nodules with prior FNA interpretation of Bethesda II, III, IV and VI as management was not significantly changed. IFS is of value for nodules with prior FNA diagnosis of Bethesda I for interpretation of nodule, and Bethesda V for planning surgery. A confirmatory diagnosis could not be rendered at IFS for lesions with follicular architecture, which comprised most of the cases in Bethesda III and IV.

How "suspicious" is that nodule? Review of "suspicious" Afirma gene expression classifier in high risk thyroid nodules.

BACKGROUND: The Afirma gene expression classifier (GEC) is being increasingly utilized to confirm the benign nature of indeterminate FNA cytology results thus avoiding unnecessary surgical procedures. However the "suspicious" result of the Afirma GEC does not classify these indeterminate nodules further in determining appropriate management. This study investigated the outcome of the thyroid nodules deemed to be "suspicious" by the Afirma GEC in a high risk population. METHODS: The pathology database was searched for all thyroid nodules with Afirma test results over a three year period, 2013-2015. All thyroid nodules with a "suspicious" Afirma GEC result were investigated. Patient medical records were retrospectively reviewed for clinical history, FNA results, radiologic findings, management and follow-up. RESULTS: Afirma result was suspicious in 69 cases. On cytologic evaluation 3.0% of the cases were non diagnostic (ND), 9% benign, 62% AUS, and 26% suspicious for neoplasm (SN). There was no follow up in 13% of cases and 87% were resected (50% lobectomies and 50% total thyroidectomies). On surgical resection 82% were benign, with 45% follicular adenoma (FA), and 37% nodular goiter (NG). The remaining 18% were malignant. CONCLUSION: The rate of malignancy in nodules suspicious by Afirma was 18.3% (11/60). The rate of malignancy in nodules suspicious for neoplasm (SN) on cytology interpretation was 31.2% (5/16). False positive rate of Afirma was 56% (32/57). We conclude that cytology interpretation has a higher rate of predicting malignancy, in nodules interpreted as SN, when compared with the Afirma test, by almost twofold Diagn. Cytopathol. 2017;45:308-311. © 2016 Wiley Periodicals, Inc.

Fine-needle aspiration biopsy of lytic bone lesions: An institution's experience.

OBJECTIVES: Fine needle aspiration (FNAB) is an effective, minimally-invasive, inexpensive, diagnostic technique. The objective of this study was to evaluate the accuracy of FNAB in the diagnosis of bone lesions. METHODS: FNABs of bone lesions diagnosed at our institution over a 2-year period were retrospectively analyzed. RESULTS: 241 samples were reviewed. Patients included 121 males and 120 females, with ages ranging from 4-95 years (mean = 66 years). Of these 241 cases, 43.2% had FNAB and 56.8% had FNAB with core needle biopsy (CNB). The cytologic diagnoses were categorized as nondiagnostic, benign, atypical, suspicious, and positive for malignant cells. Total of 84.3% of FNABs were diagnostic. Of the malignant cases, 78.5% were metastases from nonosseous primary sites, 17.1% were lymphoproliferative lesions, and 4.4% were primary bone tumors. The most common site of metastasis was the pelvic bones (43.5%) followed by the vertebral column (38.7%). Breast (21%), lung (12.7%), and prostate (11.3%) were the most common identifiable primary site in metastatic cases. FNA smears and cell blocks allowed identification of metastatic lesions in 94.3% cases with immunohistochemistry (IHC). Obtaining a concomitant CNB did not result in a statistically significant increase in overall diagnostic yields (P = .20), ascertaining presence of metastatic lesion (P = .96) or ability to identify site of primary tumor in cases of metastasis (P = .53) compared to FNAB alone. Diagnostic accuracy was improved by reviewing clinical history, performing cell block, and IHC. CONCLUSIONS: FNAB is a reliable tool for diagnosis of bone lesions with comparable diagnostic sensitivity to CNB.

Focal adhesion proteins as markers of malignant transformation and prognostic indicators in breast carcinoma.

Focal adhesion kinase (FAK) is one of the central signaling molecules found at focal adhesion sites, which are specific areas on the cell membrane where cells attach to extracellular matrix proteins. Focal adhesion kinase interacts with multiple signaling and adaptor molecules and effects several signaling pathways. Overexpression of FAK and its substrate c-Src has been implicated in malignant transformation and acquisition of an invasive tumor phenotype of different tissues. Overexpression of the multidomain protein paxillin, which is also a FAK ligand and a c-Src substrate, has been associated with less malignant tumor behavior. The purpose of this study was to analyze the involvement of integrin signaling molecules FAK, c-Src, and paxillin in malignant transformation of the breast epithelium. Using phosphospecific antibodies FAK-pY(397) and Src-pY(416), we demonstrated that neither activation of FAK nor activation of c-Src correlates with development of invasive tumor properties. However, activation of both FAK and c-Src correlates with malignant transformation. We further demonstrated that overexpression of paxillin also correlates with malignant transformation and is a marker of a less invasive tumor phenotype. Using tissue microarray, we demonstrated that expression and activation of paxillin inversely correlated with lymph node metastases and lymphovascular invasion, respectively. No correlation between paxillin expression and activation and tumor grade, estrogen, progesterone, and Her2/Neu receptor expression was found. In summary, focal adhesion proteins FAK and c-Src can be used as markers of malignant transformation in epithelial cells but not invasive phenotype, whereas expression and activation of paxillin may represent a good prognosticator in breast carcinoma.

Predicting histological subtypes of follicular variant of papillary thyroid carcinoma based on cytomorphology. Can cytomorphology optimize use of molecular testing?

INTRODUCTION: Follicular variant papillary thyroid carcinoma (FVPTC) can be further subclassified into one of 3 subtypes: non-invasive encapsulated FVPTC, invasive encapsulated FVPTC, and infiltrative FVPTC. Longitudinal and molecular studies have demonstrated that, in terms of both molecular profiles and prognosis, encapsulated FVPTC is comparable to follicular adenoma, invasive FVPTC to follicular carcinoma, and infiltrative FVPTC to classic PTC. To improve triaging and prevent overtreatment of patients with FVPTC, we sought to determine cytologic features likely to occur within each subtype. METHODS: A laboratory database search from 2010-2015 was conducted to identify patients with biopsy-proven FVPTC and prior fine-needle aspiration. Surgical specimens were reviewed to determine the appropriate subcategorization. Accompanying cytology reports were reviewed for features common in classic PTC and follicular neoplasms. RESULTS: Encapsulated variants were more likely to be graded as Bethesda category 4 compared with invasive or infiltrative variants. In contrast, infiltrative variants were more likely to be graded as Bethesda categories 5 and 6 compared with invasive or encapsulated variants. Compared with the encapsulated variant, infiltrative FVPTC was more likely to have nuclear pseudo-inclusions (31.82% versus 8.11%, P = 0.0468) and less likely to have microfollicular architecture (22.73% versus 54.05%, P = 0.0374). CONCLUSION: This study identified cytomorphologic differences between encapsulated and infiltrative FVPTC. With a higher threshold of suspicion for FVPTC, improved awareness of the differences between these subtypes and incorporation of molecular testing, it is likely that the Bethesda category can be revised and patient triaging can be significantly improved.

Two-tiered subdivision of atypia on urine cytology can improve patient follow-up and optimize the utility of UroVysion.

BACKGROUND: The annual incidence of urothelial carcinoma continues to increase, and it is projected that greater than 70,000 new cases will occur in the year 2015. However, as much as 23% of cytologic specimens will demonstrate some degree of atypia without meeting the criteria for urothelial carcinoma and thus will be reported as atypical. METHODS: The authors conducted 2 laboratory information searches and 1 survey. In total, 311 patients who had atypical cytology-biopsy pairs available were identified from the initial data search. The second data search identified 942 patients who had fluorescence in situ hybridization (FISH) results available. RESULTS: There was fair agreement between FISH results and cytology results (κ = 0.34; 95% confidence interval, 0.27-0.41). The analysis did not reveal any benefits of using additional atypical subcategories beyond the 2 suggested in the literature. It was determined that 2 strategies would provide an optimal balance: standardizing patient management and facilitating the adoption of universally recognized templates. CONCLUSIONS: When combining cytology and the 2-tiered atypical classification system with FISH testing, a marked increase in sensitivity and an accompanying decrease in specificity were observed compared with either test individually. Thus, highly sensitive FISH testing may help to identify high-risk patients among those in the group with uncertain atypical findings.

The impact of subdividing the "atypical" category for urinary cytology on patient management.

INTRODUCTION: The purpose of the study is to determine the impact of subdividing the "atypical" cytology interpretation into two groups: Atypical urothelial cells of uncertain significance (AUC-US) and Atypical urothelial cells suspicious for high-grade urothelial carcinoma (AUC-H/SHGUC), on management of patients with no prior history of UC. MATERIALS AND METHOD: This is a retrospective study of "atypical" urine cytology with subsequent tissue examination occurring within six months. Cytology reports with "atypical" interpretation were reclassified into AUS-UC and AUC-H based on morphologic features identified by the Johns Hopkins system and the Paris system for urine cytology. Follow-up and categorical outcomes were compared between the reclassified AUC-US and AUC-H groups. RESULTS: There was no significant difference (P < 0.4539) in the rate of cytology follow-up, the follow-up cytology result (P < 0.1845), or time between follow-up cytologies (P < 0.0869) between the reclassified atypical group of AUC-H and AUC-US. There was a significant association (P < 0.0001) of rate of malignancy with the reclassified AUC-H (87.18%) compared to the AUC-US (58.68%) groups. CONCLUSION: There was no difference in follow-up between the AUC-H and AUC-US, however there was a difference in the rates of malignancy in the two groups. The AUC-H group is similar to the SHGUC group of the Paris system and can be considered as such, whereas the AUC-US group should continue to be considered atypical. We conclude that reclassification of the "atypical" category into AUC-US and AUC-H/SHGUC can reduce the rate of atypia and help in focused follow-up and targeted management. Diagn. Cytopathol. 2016;44:477-482. © 2016 Wiley Periodicals, Inc.

Accuracy and risk of malignancy for diagnostic categories in urine cytology at a large tertiary institution.

BACKGROUND: At a high-volume center, it became necessary to provide benchmarks for the accuracy and risk of malignancy per urine cytology diagnostic category. The additive sensitivity for the determination of the residual risk of disease was calculated with the goal of determining the performance of cytology and optimal triage, including the number of urine samples, before the detection of malignancy in surveillance patients. METHODS: A 2-year laboratory information system-based search was conducted, and it yielded 587 subjects (695 biopsy and cytology pairs) with histological follow-up. The sensitivity and specificity of cytology for urothelial malignancy, the risk of malignancy per diagnostic category, the additive sensitivity, and the time for conversion from a negative initial cytology result to a positive cytology result were examined. RESULTS: The overall average sensitivity and specificity of cytology were 48.9% and 83.0%, respectively. The additive sensitivity increased with each subsequent cytology and peaked with the third cytology. A median conversion time of 22.2 months from a negative initial cytology result to a positive cytology result and a decline in predictive positive cytology after the fourth cytology were noted. Subcategorization of the atypical category failed to show statistical significance in predicting outcomes of biopsy. Surveillance subjects, as compared to primary subjects, showed a higher sensitivity for the detection of high and low grade cancers. CONCLUSIONS: The findings suggest that atypia favoring malignancy is being appropriately flagged. However, further definition of the atypical category is needed to increase specificity with a better qualitative or quantitative morphological algorithm. This study provides a risk of malignancy for each category for benchmarking and clinical triage. The data suggest that follow-up should include at least 4 consecutive urine specimens over a period of 22.2 months.

Biophysical and microscopic analysis of homologous dermal and fascial materials for facial aesthetic and reconstructive uses.

OBJECTIVES: To evaluate the microscopic structure and physical properties of homologous tissue grafts commonly used in aesthetic and reconstructive facial plastic surgery in order to determine specific properties of these materials that may affect their performance in vivo. METHODS: Two decellularized dermal materials (AlloDerm and DuraDerm) and 2 fascia lata tissue grafts (Tutoplast and cadaveric fascia lata) were examined by light microscopy (hematoxylin-eosin and Movat staining) and scanning electron microscopy. The physical properties of these materials were also examined for thickness, maximum sustainable load, strain, conformability, and elasticity. RESULTS: Significant differences in microscopic appearance existed between the 2 dermal materials and the 2 fascial materials. AlloDerm and Tutoplast fascia lata retained architecture closer to that of untreated tissue than did DuraDerm and cadaveric fascia lata, respectively. Tutoplast fascia lata and AlloDerm were also stronger than cadaveric fascia lata and DuraDerm, respectively. AlloDerm retained significantly more elasticity than DuraDerm. CONCLUSIONS: AlloDerm and Tutoplast fascia lata retain more natural architecture and physical properties than do DuraDerm and cadaveric fascia lata, respectively. These differences clearly show the effect of the specific processing of these materials. The alteration in architecture and the degradation of the physical properties of DuraDerm and cadaveric fascia lata may hinder the performance of these grafts in vivo. Further studies on these materials in humans are currently under way.

Malignant rhabdoid tumor of the kidney in a child: report of a case with recurrence in the contralateral kidney.

BACKGROUND: Malignant rhabdoid tumor (MRT) of the kidney is a rare and aggressive neoplasm with a controversial histogenesis. Although their immunohistochemistry may be diverse, the rhabdoid phenotype and mutations of the INI1 gene are consistently exhibited by MRTs regardless of their location. CASE: MRT recurred in the contralateral kidney in a 12-month-old child within 6 months after the initial histologic diagnosis, nephrectomy and autologous stem cell transplant. The presence of widespread metastases at the time of the recurrence precluded any further chemical and surgical diagnostic or therapeutic intervention. CONCLUSION: To the best of our knowledge, only a few cases describing the cytologic diagnosis of MRT of the kidney in a child have been reported. This case illustrates the usefulness of cytologic diagnosis in an MRT recurrence.

Laryngeal myxoma: a case report and review of the literature.

Myxomas are a rare benign neoplasm of uncertain mesenchymal cell origin, typically involving the heart. Laryngeal myxomas are uncommon, and are usually misdiagnosed as laryngeal polyp. To the best of our knowledge, there are only nine reported cases in the English literature. We report a case of a laryngeal myxoma presenting clinically as a left vocal cord polyp in a 77 year old male, and review the literature related to this rare entity.

Isolated adrenal cryptococcosis, diagnosed by fine-needle aspiration biopsy: a case report.

This report documents a case of isolated adrenal gland cryptococcosis without the often reported component of concomitant meningitis or Addison's disease in an immune competent patient. Furthermore, both the patient's lung cancer and adrenal infection with cryptococcus were incidentally discovered during work-up for syncope in the setting of hyponatremia. This case also underscores the diagnostic value of fine-needle aspiration biopsy in this unusual presentation.

Rosai-Dorfman disease. Report of a case presenting as a midline thyroid mass.

To the best of our knowledge, this is the only reported case of isolated involvement by Rosai-Dorfman disease (RDD) of small, anterior cervical-midline lymph nodes, clinically presenting as a thyroid mass. Thyroid parenchymal involvement by RDD has been reported in only 3 cases in the literature. The present case shows involvement of RDD of a pretracheal and thyroid isthmic lymph node in a 38-year-old woman. The progressively enlarging, anterior neck mass was diagnosed as "lymph node" on a fine-needle aspiration biopsy specimen and subsequently interpreted to be an isthmic cyst on ultrasonography. A magnetic resonance imaging scan revealed foci of nodularity in the thyroid isthmus and pretracheal lymph node. Excisional biopsy of the 2 masses revealed typical features of sinus histiocytosis with massive lymphadenopathy in the lymph node. Review of the patient's previous fine-needle aspiration biopsy specimens also revealed the presence of similar features. Currently, the patient is well and has no other manifestation or recurrence of RDD.