The prognostic and predictive value of Her2/neu and the hormone receptors in patient with primary or metastatic breast cancer is essential for a favorable outcome of treatment. We have been experiencing increasing requests to test cytologic specimens for these markers in patients with metastatic breast carcinoma. A recent study threw some doubts on the validity of such testing using cell blocks. In this study we compared our immunohistochemical Her2/neu, ER and PR testing performed on 42 formalin-fixed, paraffin-embedded cell blocks from 27 fine needle aspirations (FNA) and 15 serous effusions of 42 patients with metastatic (n = 38) and primary (n = 4) breast carcinoma to the test results obtained on tissue sections. In seven cases the Her2/neu immunohistochemistry (IHC) results on cell blocks were also compared with Her2/neu fluorescence in situ hybridization (FISH) on tissue or cell block. The study revealed 100% correlation for positive and negative Her2/neu results. For ER testing the results showed 85.7% sensitivity, 100% specificity, 100% positive predictive value (PPV), and 85.7% negative predictive value (NPV). For PR testing the results showed 80% sensitivity, 100% specificity, 100% PPV, and 88.8% NPV respectively. In conclusion, IHC for Her2/neu, ER and PR performed on formalin-fixed, paraffin-embedded cell blocks prepared from fresh FNA and serous fluid is reliable in predicting the expression of these markers when correlated with IHC and FISH performed on the corresponding tumor tissue.

Background: SARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear.Method: We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to create in vitro lung models of COVID-19.Results: Infected ALO-monolayers best recapitulated the transcriptomic signatures in diverse cohorts of COVID-19 patient-derived respiratory samples. The airway (proximal) cells were critical for sustained viral infection, whereas distal alveolar differentiation (AT2→AT1) was critical for mounting the overzealous host immune response in fatal disease; ALO monolayers with well-mixed proximodistal airway components recapitulated both.Conclusions: Findings validate a human lung model of COVID-19, which can be immediately utilized to investigate COVID-19 pathogenesis and vet new therapies and vaccines.Funding: This work was supported by the National Institutes for Health (NIH) grants 1R01DK107585-01A1, 3R01DK107585-05S1 (to SD); R01-AI141630, CA100768 and CA160911 (to PG) and R01-AI 155696 (to PG, DS and SD); R00-CA151673 and R01-GM138385 (to DS), R01- HL32225 (to PT), UCOP-R00RG2642 (to SD and PG), UCOP-R01RG3780 (to P.G. and D.S) and a pilot award from the Sanford Stem Cell Clinical Center at UC San Diego Health (P.G, S.D, D.S). GDK was supported through The American Association of Immunologists Intersect Fellowship Program for Computational Scientists and Immunologists. L.C.A's salary was supported in part by the VA San Diego Healthcare System. This manuscript includes data generated at the UC San Diego Institute of Genomic Medicine (IGC) using an Illumina NovaSeq 6000 that was purchased with funding from a National Institutes of Health SIG grant (#S10 OD026929).

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SARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear. We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to create in vitro lung models of COVID-19. Infected ALO-monolayers best recapitulated the transcriptomic signatures in diverse cohorts of COVID-19 patient-derived respiratory samples. The airway (proximal) cells were critical for sustained viral infection whereas distal alveolar differentiation (AT2→AT1) was critical for mounting the overzealous host immune response in fatal disease; ALO monolayers with well-mixed proximodistal airway components recapitulated both. Findings validate a human lung model of COVID-19 which can be immediately utilized to investigate COVID-19 pathogenesis, and vet new therapies and vaccines.

Histiocytic sarcoma (HS) is a rare, aggressive malignancy. Lesions previously called HS were typically non-Hodgkin lymphomas, not HS. As such, chemotherapy directed at lymphoid neoplasms was frequently successful, but it is unclear if these regimens are ideal for HS. We present a 33-year-old African gentleman who underwent sequential renal transplants for glomerulonephritis. He subsequently developed HS of the upper airway and multiple cutaneous sites. The patient received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) followed by salvage ifosfamide, carboplatin, and etoposide (ICE) but had continuous progression of cutaneous involvement. Cladribine, high-dose cytarabine, G-CSF, and mitoxantrone (CLAG-M) yielded a partial response with near resolution of disease. Ultimately, the patient achieved a complete remission after myeloablative allogeneic hematopoietic stem cell transplant. HS occurring after solid organ transplant raises the possibility of HS as a potential posttransplant malignancy. The use of CLAG-M has not been reported in HS. In this case, histiocyte-directed chemotherapy with CLAG-M was superior to lymphoma-directed regimens.