Sanjay Mukhopadhyay

1. Introducing a new thread: super basic lung pathology for PGY1s, with arrows. If you are a PGY1, leave a comment and I will tag you in a future post. A hamartoma is a disorganized mix of overgrown normal tissues (in their normal location) that creates a mass. Good news: they are benign! #pathology #pulmpath #tweetorial #pathtweetorial #sblppgy1

@rovingatuscap @Mvgs1706 @LaraHarikMD @h_alahmadie @drmehrarohit @LJTafeMD @01sth02 @sza_jhcyto @Sara_Jiang @KMirza Rochester, NY

Mornings in the Midground #NYC 5.15.2026 #urbanpalette 🎨

10/ No!! (Cryptococcosis)

9/ NO!!! (Aspiration of food and other particulate matter) Reference: pubmed.ncbi.nlm.nih.gov/17460460/

New thread: is it consistent with sarcoidosis? 1/ Yes!

Palate. What is your diagnosis? 🔎 Poll below 🗳️👇 #PathPuzzle 🕵️‍♂️ @UMichPath #Pathology #PathX #PathTwitter

@GuannanTiffany @JHUPath #PathTweetAward

🧩 Lost in the body maze — testis riddle I’m in the testis… but am I really testis? 🤔 A little embryology. Where am I? #DxMindMap #Testistumor #GUPath #PathTwitter @JHUpath

@grok @grok I mean there is also interest in POU2F3, both these immunos were introduced recently.

POU-domain TFs (like POU4F3/Brn-3c) are master regulators of Merkel cell differentiation, acting downstream of ATOH1 to activate late genes for maturation. MCC retains this exact transcriptional program, so tumor cells show strong nuclear expression—making it an excellent IHC marker (98%+ sensitive/specific per recent validation). Not sudden: transcriptomics flagged it, new antibodies + studies (Karpinski Mod Pathol 2025) made it practical now. Like TTF1 or CDX2 before it.

@grok this is salt-and-pepper nuclear chromatin. Tell us more about this

@grok @grok why are POU domain transcription factors being used in immunohistochemistry all of a sudden? Is there an easy explanation?

POU4F3 (BRN3C) is a POU-domain transcription factor essential for normal Merkel cell differentiation and maturation. It functions downstream of ATOH1 as a pioneer factor, activating late-stage genes (e.g., KRT20, Piezo2) in epidermal progenitors that give rise to Merkel cells. MCC recapitulates this lineage, so tumor cells retain strong nuclear expression—independent of MCPyV status—explaining its high sensitivity as an IHC marker.

@grok @grok why is this marker positive in Merkel cell carcinoma?

POU4F3 (BRN3C) is a nuclear transcription factor recently shown to be a highly sensitive/specific IHC marker for Merkel cell carcinoma (MCC). Karpinski et al. (Mod Pathol 2025): 98.7% sensitivity (151/153 MCCs, both MCPyV+ & -) and 98.3% specificity vs mimics (only 3/180 non-MCCs weakly+ , mostly rare SCLC). Strong nuclear staining; very useful for SLN mets detection—even single cells. Pairs well with CK20/synaptophysin.

@grok @grok tell me more about POU4F3 as a marker of Merkel cell carcinoma

One novel immunostain for Merkel cell carcinoma is **INSM1** (insulinoma-associated protein 1). It shows strong nuclear positivity in MCC and other neuroendocrine tumors, often more sensitive and easier to interpret than traditional markers like synaptophysin or chromogranin—especially useful in CK20-negative or cytologic cases like this. Another emerging marker is POU4F3 (recently described as highly sensitive/specific).

@grok name a novel immunostain for Merkel cell carcinoma @grok

Salt-and-pepper nuclear chromatin describes the finely stippled, granular appearance of nuclei under the microscope—small clumps of heterochromatin scattered like salt and pepper grains. It's a hallmark of neuroendocrine differentiation, classically seen in: - Small cell carcinomas (esp. lung) - Carcinoid tumors - Merkel cell carcinoma - Some medullary thyroid carcinomas In cytologic preps like this one, the nuclei often show molding, scant cytoplasm, and inconspicuous nucleoli. Great example!

@RazaHoda #PathTweetAward

Pagetoid Spread of DCIS ⛏️👷‍♂️🔬 Atypical ductal epithelial cells undermining the ductal epithelium of large ducts in a pagetoid distribution. #PathX #PathTwitter #breastpath