Amphophilic cytoplasm

• Nonepithelial, neural crest derived neuroendocrine neoplasms arising from the adrenal medulla (pheochromocytoma) and extra-adrenal paraganglia • Composed of paraneuronal peptide hormone secreting neuroendocrine cells • Histologically similar, regardless of location • 2 categories: • Parasympathetic: arises predominately in the head and neck • Sympathetic: arises in the retroperitoneum, thorax and pelvis • Nonepithelial neuroendocrine tumors producing dopamine, epinephrine, norepinephrine and other peptide hormones • Occuring at almost any location, except within the brain and bones • All tumors have metastatic potential; they are referred to as metastatic or nonmetastatic instead of benign or malignant • Because of frequency of multifocal primary tumors, metastatic deposits should only routinely be considered as such at sites where normal chromaffin tissue is not present, including bone, brain and lymph node; however, metastatic disease can involve any organ • Regrowth or recurrence in the surgical bed should not be identified as metastatic pheochromocytoma / paraganglioma • At least 20% are multiple (bilateral or multicentric) • Tumor with highest degree of heritability among all human neoplasms • Hereditary predisposition due to germline mutation present in almost 40% of tumors (see • Associated with various syndromes and familial conditions, known as familial pheochromocytoma and paraganglioma syndromes, including: • SDHx related syndromes ( SDHB, SDHD, SDHA, SDHC and...

Differential Diagnosis • • • • • • • • • • • • CD23 85% 2% 8% 0-30% on immunohistology but up to 60% weak positive on flow 0-25% CD5 80% 80% 0% 5% 0% bcl1 2% 85% 0% 0% 0% CD10 0% 2% 2% 3% 85% CD43 80% 85% 35% 10-30% 7% bcl2 95% 95% 65-90% >50% 90% • CD23 staining refers to lymphoid staining • Follicular dendritic cells stain in many processes • bcl1 • Blastic mantle cell lymphoma 100% • Hairy cell leukemia 41% • CD43 stains only 2% of splenic marginal zone lymphoma Irregular nuclear membranes Round nuclei Residual germinal centers may be prominent Proliferation centers present Expanded mantle zone around germinal centers variably present No mantle zone pattern Scattered histiocytes Histiocytes not prominent bcl1 85% bcl1 2% CD23 2% CD23 85% Blastic transformation Large cell transformation Some mantle cell lymphomas have been reported to have proliferation centers; these are better considered as SLL/CLL Proliferation centers absent Proliferation centers frequent Plasmacytoid differentiation marked Plasmacytoid differentiation variable CD5 5% CD5 80% CD23 0-30% on immunohistology but up to 60% weak positive on flow CD23 85% Enlarged marginal zone Diffuse effacement Pale monocytoid cells Small round lymphocytes May have residual germinal centers Proliferation centers frequent CD23 8% CD23 85% CD5 negative CD5 80% CD43 35% (Splenic 2%) CD43 80% Both may involve the GI tract and other mucosal sites Distinct nodular pattern Vague proliferation centers Nodules composed of cleaved...

Histologically, cerebellar folia were separated consistently by thick sheets of neoplastic cells, which were round, 10-20 pm in diameter, with a small amount of well-defined eosinophilic to amphophilic cytoplasm and round or cleaved nuclei with clumped chromatin and inconspicuous nucleoli (Figs 1A, 1B).

Contents • 1 Pathology simplified • 1.1 Blue & pink • 1.2 Three questions • 2 Terms • 2.1 Staining • 2.2 Morphologic patterns • 2.3 Nuclear destruction words • 2.4 Erosions and ulcers • 2.4.1 Microscopic - erosion • 3 The general differential diagnosis • 3.1 Features of malignancy • 3.1.1 Cytologic features of malignancy • 3.1.2 Other features • 3.2 General differential diagnosis of malignant lesion • 3.3 A general clinico-histomorphologically motivated differential diagnosis of malignancy • 3.3.1 Morphologic categorization • 3.3.1.1 Factors to consider • 3.3.1.1.1 Types of cells • 3.3.1.1.2 Dyscohesive versus cohesive • 3.3.1.2 Probable category by morphology • 3.4 A practical histomorphologic differential diagnosis of malignancy • 3.4.1 General morphologic DDx of malignancy • 3.4.2 Modified general morphologic DDx of malignancy • 4 Differential diagnosis by site • 5 Finding the elements • 5.1 Mitoses • 5.1.1 Images • 5.1.2 Phases of mitosis • 5.2 Neutrophils • 5.3 Lymph node metastasis • 5.4 Signet ring cell carcinoma • 5.4.1 Images • 5.5 Necrosis • 6 Granulomas • 7 Common morphologic problems • 7.1 DDx of pink stuff (on H&E) • 7.1.1 Images • 7.1.2 Smooth muscle cells (SMCs) vs. fibrous tissue • 7.2 Pigmented material • 7.2.1 Stains that can help sort it out • 8 Staining • 9 Immunohistochemistry • 10 Food and pathology • 11 Tumour remaining • 12 Clinician talk • 12.1 Performance status • 13 Pathology & pathologists • 13.1 Fixation & lifestyle • 13.2 Malignancy & inflamma...

Cutaneous soft tissue tumors with epithelioid features present a diagnostic challenge given that many entities in this category are rare, and they show morphologic overlap with significantly more common cutaneous epithelial and melanocytic neoplasms. The challenge is compounded by overlapping expression of epithelial or melanocytic markers in some of these entities. A broad spectrum of primary cutaneous epithelioid soft tissue tumors exists, including benign and malignant counterparts of tumors with various differentiation including melanocytic, peripheral nerve sheath, angiomatous, fibrohistiocytic, and myoid or myoepithelial, in addition to translocation-associated tumors lacking a derivative tissue type. Given this spectrum, an initial targeted immunohistochemical panel for epithelioid dermal and subcutaneous neoplasms is recommended, covering a broad spectrum of differentiation. In diagnostically challenging cases, select molecular studies can be employed to make critical distinctions between entities sharing morphologic and immunohistochemical properties. Due to sometimes marked differences in prognosis and treatment, knowledge and familiarity with epithelioid soft tissue tumors is key for any surgical pathologist who evaluates skin and subcutaneous biopsies and excision specimens. This concise review provides brief descriptions, key diagnostic features, and important modern ancillary studies for the diagnosis of non-epithelial, non-melanocytic cutaneous tumors that c...

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