David Klingman on LinkedIn: #histology #pathology (2024)

David Klingman

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2024.08.29 #histology for #pathology studytoday I'd like to focus on benign cystic salivary tumors and highlight 3 elements of their morphology:first, a careful examination of nuclear features to distinguish these from malignant counterpartssecond, a short discussion of malignant counterparts that may mimic these tumorsthird, as we'll see in the fourth case, a careful examination of the stoma to exclude malignancy--images 1-2, signed out as cystadenoma; the morphology is reminiscent of respiratory type mucosa [but variants may demonstrate squamous, cuboidal and other morphologic features]other cystic salivary tumors and developmental cysts that may mimic this lesion (with the histologic features in this case) include bronchogenic cyst and respiratory metaplasia in salivary duct cysts--images 3-4, signed out as oncocytic papillary cystadenoma; I draw your attention to this case to show the similarity to the first case and to highlight that perhaps these are not distinct lesions and that a number of adjectives can be used to describe these cases for academic purposes but that these distinctions likely do not have clinical significanceof note: given that mucoepidermoid carcinoma (MEC) has been reported to have an oncocytic variant, immunohistochemical stains and special stains may be considered [mucicarmine, PAS with diastase, p63] and the characteristic MAML2 gene rearrangement may help distinguish MEC in challenging cases that may be lacking mucocytes--images 5-6, signed out as oncocytic papillary cystadenoma with lymphoid stroma this may be considered equivalent to Warthin tumor of the parotid gland; however in this case the lesion was present beneath the oral buccal mucosa, sparking debate between our residency program director and the chief resident, who was me at the time [I did not win the debate] suggesting that we could include the term Warthin tumor based on its location outside the parotid gland--images 7-9, signed out [without debate, as this case was from the parotid gland] as Warthin tumor/oncocytic papillary cystadenoma with lymphoid stromathe characteristic histologic features are all present: a bilayer of cuboidal to columnar oncocytic cells [and in this case image 8 highlights a more squamous appearance toward the lower right, which is not uncommon] and a stroma with abundant lymphocytes often (and in this case) forming well developed lymphoid follicles with well-developed mantle zonesexamination of the stroma, as I mentioned, is important; lymphoma has been reported to arise in these cases, so I've included image 9 to highlight the well developed follicle (complete with more optically clear tingible body macrophages) and mantle zone

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    2024.09.02 #histology for #pathology studyas I will be sharing cases for the next four days that I consider outside my scope of expertise, I will preface by saying the following:I will be very cursory in the review and highlight just a few features, just a few immunohistochemical stains, and a few major cytogenetic findingsI recommend in any of these cases encountered in real life to have a hematopathologist or general pathologist with skill manage or at least review and counter sign the casestissue management is important; fresh and/or frozen tissue should be set aside for flow cytometry and genetic analysis--images 1-4, plasmablastic lymphoma [often extranodal, often associated with immunosuppression, often associated with EBV]morphology is typically plasmablastic or immunoblastic phenotypeIHC: CD138, CD38, MUM1, CD79a, EBER, high proliferation indexcytogenetics: myc rearrangements image 2 highlights the plasmablastic phenotype, image 3 highlights areas of necrosis, image 4 highlights areas of crush artifact often identified in biopsy specimens of lymphoproliferative disorders --images 5-8, Burkitt lymphoma [often extranodal, often associated with EBV]morphology consists of monotonous intermediate sized cells with interspersed tingible body macrophages imparting the so-called "starry sky" appearance IHC: reactive for CD45, B cell markers, myc, with high proliferation index [often 100%]cytogenetics: t(8;22) IgH-myc rearrangementsimage 6 highlights the presence of tingibke body macrophages, image 7 highlights areas of necrosis, image 8 highlights invasion and destruction of bone [this case Had an intraosseous component]

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    #pathology #radiology

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    #mentorship #education #dentistry

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    2024.09.01 #histology for #pathology studyfor this last week, I will present a cursory review of lymphomas, starting with a comparison of hyperplastic oropharyngeal tonsil and extranodal marginal zone lymphoma (MZL)before showing the cases, I will comment and advise students who encounter potential or actual lymphomas, to consider engaging the expertise of a hematopathologist or a general pathologist with skills in this area --images 1-4 highlight the features of hyperplastic oropharyngeal tonsil: multiple crypts and well-developed underlying lymphoid follicles with polarized mantle zones [image 1], unremarkable stratified squamous epithelium at the mucosal surface [image 2] and 'reticulated' epithelium with lymphocytes (antigen presenting cells) percolating into the epithelium that serve to communicate the environment to the immune system [image 3]; image 4 is a 400x view of a lymphoid follicle highlighting the germinal center at the lower left and the mantle zone crossing diagonally through the center of the imagealthough not present in this case, bacterial colonies are often identified; these represent what often become calcified concretions that clinically may develop into tonsillolithsimages 5-6 represent adenoid or what may be referred to as nasopharyngeal tonsil; I included these images to highlight the respiratory type (pseudostratified ciliated columnar) epithelium at the surface and as for oropharyngeal tonsil the numerous well developed lymphoid follicles with polarized mantle zones--images 7-9 represent what was signed out by a general pathologist as extranodal marginal lymphoma; in this case, context is important since the specimen was from a reported mass at the base of the tonguemy admission is that earlier in my career, I may have identified what appeared to be an epithelial-lined cyst [larger tissue fragment in image 7] and been drawn to a diagnosis of lymphoepithelial cyst; as I reviewed more and more cases from the oropharynx, I began to engage the general pathologists I worked with whenever I saw anything unusual or an absence of well-developed lymphoid folliclesimage 8 highlights the importance of examining the epithelium; in this case there were no concerning features for carcinomaimage 9 highlights diffuse population of small lymphocytes without follicle and germinal center formation; there is also some amorphous background material representing amyloid--this will my first opportunity to highlight the importance of 3 elements in the diagnosis of lymphoma:tissue management, including collection of fresh tissue for flow cytometry and/or cytogenetic analysis; communication with the pathologist/laboratory is importantthe use of immunohistochemistry [MZL such as this case is nonreactive for many of the markers identified in other lymphomas]flow cytometry for identification of cytogenetics [MZLs typically harbor t(14;18) IgH-bcl2 rearrangements]

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  • David Klingman

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    2024.08.31 #histology for #pathology studytoday I'll present a comparison between cervical lymphoepithelial cyst and a cystic lymph node of the neck representing metastasis of oropharyngeal carcinoma--image 1 is a 'whole slide' photograph of a case signed out as "cervical lymphoepithelial cyst"images 2 and 3, 20x views of the cyst; the highlight feature is that the cyst is surrounded by lymphoid stromaimage 4, 400x, highlights the cyst lining consisting of stratified squamous epithelium with a well developed basal layer; a surrounding lymphoid stroma is evident--image 5 is a 'whole slide' photograph of a case signed out as "squamous cell carcinoma, non-keratinizing, p16 reactive"images 6-7, 20x views of the lymph node sampled; at this magnification, the histologic features are similar to those of the first caseimage 8, 400x, highlights a cyst-like lining consisting of round to ovoid epithelial cells without normal maturation from a basal layer; in this case there was concern for metastasis, so p16 [a specific and sensitive surrogate for HPV infection] was performed and was reactive throughout the epithelial layer [PET scan revealed a PET avid (metabolically active) lesion in the oropharynx which turned out to be non-keratinizing p16 reactive squamous cell carcinoma--image 9 is presented to demonstrate the features of HPV-related non-keratinizing squamous cell carcinoma of the oropharynx; though not identical to the histologic features in images 4-8, the nuclear features are somewhat similar (round to ovoid/elongated nuclei, hyperchromatism) and there are multiple mitotic figures; p16 was reactive in both the nuclei and cytoplasm--for the final series of teaching cases over the next few days, I will transition first to a comparison of hyperplastic oropharyngeal tonsil vs marginal zone lymphoma, followed by a 4-day examination of lymphomas to complete the entire series on 5 September

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  • David Klingman

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    2024.08.30 #histology for #pathology studya cursory examination of mixed tumor (pleomorphic adenoma) of the salivary glands [a complete examination could take several posts, so I'm just going to highlight a few things and hopefully help distinguish benign salivary gland tumors from malignant salivary gland tumors]a few things to consider, some of which I will highlight in the images:myoepithelial cells may different in more morphology [including spindle, epithelioid, plasmacytoid and squamous]the stroma may be myxoid, chondroid, or collagenous and may contain tyrosine crystals, fat, or bonethe presence of ducts and duct-like structures is common [and as I will show in one of the cases may distinguish mixed tumor from myoepithelioma] and as a so-called 'biphasic' tumor, the ducts may present as separate duct and myoepithelial cell layers [and resemble the morphological structures seen in epithelial-myoepithelial carcinoma, potentially providing some challenge if carcinoma ex mixed tumor is a concern]carcinoma ex mixed tumor should be considered if abnormalities or pleomorphism are noted, or if there is extension of tumor beyond a capsule [the literature tends to report up to 8mm of extracapsular invasion as a delineator for absence or presence of metastasis]immunohistochemistry may be helpful [generally differential cytokeratins and S100 will be reactive and markers for other tumors (such as p63/p40, DOG1, mammaglobin) will help distinguish mixed tumors from a number of malignancies]PLAG1 and HMGA2 mutations may be identified in both mixed tumor and carcinoma ex mixed tumor; TP53 mutations may help distinguish malignancy--images 1-2, signed out as mixed tumor; I selected these images to highlight the myxoid stroma and somewhat squamous appearance to the intervening myoepithelial cellsimages 3-4, signed out as mixed tumor; I selected these images to highlight myxoid to chondroid stroma, epithelioid to plasmacytoid myoepithelial cells, and tumor seeding [which may occur as a complication of surgery and should not necessarily lead immediately to a malignant diagnosis]images 5-6, signed out as mixed tumor I selected these images to highlight the presence of ducts and duct like structures with clearly defined luminal and basal myoepithelial cells [which could raise suspicion for epithelial-myoepithelial carcinoma ex mixed tumor]images 7-8, signed out as myoepithelioma; I selected these images to highlight the absence of ducts and duct like structures and the common nesting and nest like structures present in this tumor; the morphology may also bring into consideration other tumors with nesting [such as paraganglioma] and the utility of using IHC

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  • David Klingman

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    reflecting on the value of my time; many of my mentors, colleagues and friends suggest balancing my time with its potential dollar value:when a friend or colleague is asking for my advice interpreting a biopsy report [especially when it's something malignant and there's going to be oncologic therapy involved] I'll take the time to answer the questions; this tends to alleviate anxiety among people who may not have a complete understanding of #pathologywhen students, interns and residents are preparing for in-service and specialty certification exams, I'll prepare study materials for them [and I release them for general consumption to improve success and improve the quality of practice]when I'm asked to speak at a professional conference [most typically for #dentistry and #medicine] I will ask for an honorarium, registration for the conference at no charge, and travel expenses

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