Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course that can arise de novo or from a low-grade B-cell lymphoma. In particular, chronic lymphocytic ...leukemia/small lymphocytic lymphoma is a very common malignancy in the Western hemisphere, and most cases of chronic lymphocytic leukemia/small lymphocytic lymphoma have an indolent course and behavior. However, 2% to 8% of chronic lymphocytic leukemia/small lymphocytic lymphoma cases transform. Histiocytic sarcomatous transformation is rare and portends poor prognosis.
To review the clinical features, morphology, and key points related to the differential diagnosis for histiocytic sarcoma. We discuss recent understanding of the biology underlying transformation.
University of Michigan case and review of pertinent literature about histiocytic sarcoma and morphologic differential diagnosis.
Histiocytic sarcoma is a rare histiocytic neoplasm that can arise as a result of transdifferentiation from low-grade B-cell lymphomas, and has a wide differential diagnosis including other histiocytic/dendritic cell neoplasms, myeloid neoplasms, lymphomas, melanoma, and carcinoma. However, some key morphologic and immunohistochemical features allow for accurate classification.
Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC) is an uncommon disorder with germline-inactivating mutations in the fumarate hydratase ( FH) gene. The kidney cancers that develop ...in patients with HLRCC are often unilateral and solitary, with a potentially aggressive clinical course; morphologic identification of suspicious cases is of the utmost importance.
To review classic morphologic features of HLRCC-associated renal cell carcinoma, the reported morphologic spectrum of these tumors and their mimics, and the evidence for use of immunohistochemistry and molecular testing in diagnosis of these tumors.
University of Michigan cases and review of pertinent literature about HLRCC and the morphologic spectrum of HLRCC-associated renal cell carcinoma.
Histologic features, such as prominent nucleoli with perinucleolar halos and multiple architectural patterns within one tumor, are suggestive of HLRCC-associated renal cell carcinoma. However, the morphologic spectrum is broad. Appropriate use of FH immunohistochemistry and referral to genetic counseling is important for detection of this syndrome.
A variety of uncommon malignant endometrial tumors can be challenging to diagnose because of overlapping morphology with more common entities. In some cases, immunohistochemical stains and/or ...molecular testing allow for more definitive diagnosis or prognostication.
To review classic morphologic features of uncommon endometrial tumors, pathologic features of these tumors and their mimics, and the evidence for use of immunohistochemistry and molecular testing in the diagnosis of these tumors.
University of Michigan (Ann Arbor) cases and review of pertinent literature about each entity.
Although each of these uncommon endometrial tumors has morphologic mimics, key histologic features, immunohistochemical stains, and molecular testing allow for accurate classification.
Renal cell carcinomas (RCCs) are a heterogeneous group of neoplasms. Recent sequencing studies revealed various molecular features associated with histologic RCC subtypes, including chromophobe renal ...cell carcinoma (ChRCC).
To characterize the gene expression and biomarker signatures associated with ChRCC.
We performed integrative analysis on RNA sequencing data available from 1049 RCC specimens from The Cancer Genome Atlas and in-house studies. Our workflow identified genes relatively enriched in ChRCC, including Forkhead box I1 (FOXI1), Rh family C glycoprotein (RHCG), and LINC01187. We assessed the expression pattern of FOXI1 and RHCG protein by immunohistochemistry (IHC) and LINC01187 mRNA by RNA in situ hybridization (RNA-ISH) in whole tissue sections representing a cohort of 197 RCC cases, including both primary and metastatic tumors.
The FOXI1 and RHCG IHC staining, as well as the LINC01187 RNA-ISH staining, was evaluated in each case for intensity, pattern, and localization of expression.
All primary and metastatic classic ChRCCs demonstrated homogeneous positive labeling for FOXI1, RHCG proteins, and LINC01187 transcript. Unclassified RCC with oncocytic features, oncocytoma, and hybrid oncocytic tumor, as well as all but two cases of eosinophilic ChRCC also stained positive. Importantly, metastatic and primary RCC of all other subtypes did not demonstrate any unequivocal staining for FOXI1, RHCG, or LINC01187. In normal kidney, FOXI1, RHCG, and LINC01187 were detected in the distal nephron segment, specifically in intercalated cells. Two cases of eosinophilic ChRCC with focal expression of FOXI1 and LINC01187, and Golgi-like RHCG staining were found to contain MTOR gene mutations upon DNA sequencing.
We demonstrate a pipeline for the identification and validation of RCC subtype–specific biomarkers that can aid in the confirmation of cell of origin and may facilitate accurate classification and diagnosis of renal tumors.
FOXI1, RHCG, and LINC01187 are lineage-specific signature genes for chromophobe renal cell carcinoma.
We performed integrative RNA sequencing analysis from >1000 renal cell carcinoma (RCC) specimens, identified genes enriched in chromophobe RCC, experimentally validated the expression pattern of the top three genes (FOXI1, RHCG, and LINC01187), and revealed that the cell of origin of chromophobe RCC is intercalated cells.
Primary Cutaneous Follicle Center Lymphoma Skala, Stephanie L; Hristov, Boris; Hristov, Alexandra C
Archives of pathology & laboratory medicine (1976),
11/2018, Letnik:
142, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Primary cutaneous follicle center lymphoma is a low-grade B-cell lymphoma that is limited to the skin at diagnosis. It has a differential diagnosis that includes systemic/nodal follicular lymphoma ...secondarily involving the skin; primary cutaneous diffuse large B-cell lymphoma leg type; reactive lymphoid hyperplasia; and primary cutaneous marginal zone lymphoma.
To review the clinical, morphologic, immunophenotypic, and genetic features of primary cutaneous follicle center lymphoma; its differential diagnosis; and the evidence that supports use of immunohistochemistry and genetic testing in the diagnosis and prognosis of this entity.
Pertinent literature regarding cutaneous B-cell lymphomas is summarized and University of Michigan cases are used to highlight characteristics of primary cutaneous follicle center lymphoma.
Primary cutaneous follicle center lymphoma is a low-grade B-cell lymphoma with distinctive features, although some cases may have elements that overlap with other lymphomas, complicating interpretation.
Aims
Distinction between well‐differentiated endometrial carcinoma (EMCA) with microglandular/mucinous features and benign endocervical microglandular hyperplasia (MGH) can be a diagnostic challenge, ...especially when tissue is limited. The immunostains used to distinguish endocervical and endometrial carcinoma are less useful when the differential diagnosis is MGH. Here, we investigate the utility of p63 and phosphatase and tensin homologue (PTEN) to aid accurate classification.
Methods and results
Cases obtained from our pathology archives included 25 EMCA with mucinous/microglandular features, 26 MGH and nine atypical microglandular proliferations. Cases were assessed for glandular architecture, presence of mucinous and/or eosinophilic luminal secretions, subnuclear vacuoles, foamy histiocytes, inflammation, squamous metaplasia, cytological atypia and mitotic activity. The presence and pattern of immunohistochemical staining for p63 and PTEN was recorded. Microglandular proliferations with cytological atypia, mitotic activity, foamy histiocytes and complex glandular architecture were more commonly seen in EMCA, while small glands, bland nuclei and subnuclear vacuoles were enriched in MGH. All MGH cases displayed p63‐positive subcolumnar reserve cells and retained PTEN expression. Four EMCA cases showed non‐specific focal p63 staining either at the surface of the tumour or in areas of squamous differentiation. p63 and PTEN immunostains accurately predicted the final diagnosis for 3 atypical microglandular proliferation cases with follow‐up.
Conclusions
While there are morphological characteristics that differentiate EMCA and MGH, there is frequent overlap between these entities. Nonetheless, the pattern and extent of p63 and PTEN can aid accurate classification. Consistent p63‐positive subcolumnar reserve cells were seen only in MGH.
Based on a study of 25 endometrial endometrioid carcinomas (EMCA, A) with microglandular and/or mucinous features and 26 microglandular hyperplasia (MGH, C) samples, the pattern of p63 immunohistochemical staining is often useful for distinction between these entities. EMCA was typically negative for p63 (B). Subcolumnar p63 staining of cervical reserve cells was seen in all MGH cases (D), while focal nonspecific p63 staining was seen in 4 EMCA cases.
•“Type 2 papillary RCC” likely represents a heterogeneous group of entities•RCC diagnosis increasingly requires exclusion of molecularly-defined tumors•New pathology guidelines suggest against ...subtyping papillary RCC•Additional changes to classification schemata are expected
Although papillary renal cell carcinoma has historically been classified as either type 1 or type 2, data from The Cancer Genome Atlas (TCGA) has demonstrated significant genomic heterogeneity in tumors classified as “type 2 papillary renal cell carcinoma” (T2PRCC). Papillary renal cell carcinoma is expected to have a favorable clinical course compared to clear cell renal cell carcinoma (CCRCC). However, tumors with poor outcome more similar to CCRCC were included in the T2PRCC cohort studied by the TCGA. The differential diagnosis for T2PRCC includes a variety of other renal tumors, including aggressive entities such as TFE3 translocation-associated renal cell carcinoma, TFEB-amplified renal cell carcinoma, fumarate hydratase-deficient renal cell carcinoma, high-grade CCRCC, and collecting duct carcinoma. Accurate classification of these tumors is important for prognostication and selection of therapy.
While most ovarian follicle cysts are <8 cm in greatest dimension, much larger follicle cysts (up to 18.5 cm) have been reported. To our knowledge, the FOXL2 mutation status of such cases has not ...been documented in the literature. Here, we report the features of a 14 cm ovarian cyst with no FOXL2 mutation detected by targeted next-generation sequencing. While adult granulosa cell tumor was the chief entity in our differential diagnosis, the absence of convincing nuclear grooves, lack of architectural variability, presence of a theca layer, and absence of FOXL2 mutation were consistent with a diagnosis of ovarian follicle cyst.
Differentiated vulvar intraepithelial neoplasia (dVIN) is a human papillomavirus-independent lesion with the potential for rapid progression to invasive squamous cell carcinoma (SCC). The ...histopathologic features of dVIN are diverse, have overlapping characteristics with lichen sclerosus (LS) and lichen simplex chronicus (LSC), and may be diagnosed by dermatopathologists or gynecologic pathologists because of the vulva's anatomic location.
To identify the salient histopathologic features of dVIN, particularly those that predict progression to SCC, and to evaluate interobserver agreement in diagnosing dVIN within the same subspecialty and across subspecialties.
One general surgical pathologist, 2 pathology-trained dermatopathologists, and 1 gynecologic pathologist blinded to the final diagnoses were asked to record 20 histopathologic features and to provide their final interpretations on cases of dVIN (n = 65), LS (n = 126), LSC (n = 112), and LS with LSC (n = 6).
Interobserver agreement for the 4 diagnoses and 10 histopathologic features was moderate. Logistic regression analysis indicated that keratin pearls, basal pleomorphism, and basal layer disarray were independent variables for diagnosing dVIN (coefficients 1.95, 1.97, and 0.91, respectively; P < .001) and progression to SCC (coefficients 1.96, 1.20, and 1.08, respectively; P < .001).
There is no single histopathologic feature pathognomonic for dVIN; however, the presence of keratin pearls, basal pleomorphism, and basal layer disarray should raise high suspicion for dVIN and concurrent SCC. Expertise in both dermatologic and gynecologic pathology is beneficial for diagnosing dVIN.
Recent studies have provided molecular confirmation that a subset of yolk sac tumors is somatically derived. Somatically derived yolk sac tumors are typically diagnosed in older women and are often ...seen adjacent to epithelial proliferations (such as endometriosis or endometrioid carcinoma) with which they share mutations. Here, we present a case of a postmenopausal woman with a yolk sac tumor and endometriosis in the right ovary, endometriosis with glandular crowding and reactive changes in the left ovary, endometrial endometrioid carcinoma, and yolk sac tumor involving the serosa of the colon. Targeted next-generation sequencing of these five tumor components demonstrated identical mutations in PTEN (p.R130G), PIK3CA (p.G1049S), FGFR2 (p.S252W), and FBXW7 (p.R689Q), suggesting that all components arose from a common precursor. The endometrial endometrioid carcinoma harbored additional exclusive mutations involving PIK3CA (p.H1048R) and CTNNB1 (p.S37F).
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