BACKGROUND: Homeobox C6 (HOXC6) is a gene that encodes for a transcription factor involved in various cellular processes, including development and differentiation, and regulates cancer progression. However, the carcinogenesis and effect of HOXC6 in lung adenocarcinoma (LUAD) still need further investigation.
METHODS: The differential HOXC6 expression levels at the mRNA and protein level were explored in multiple public datasets, including The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) dataset. Gene Expression Omnibus (GSE31210), International Cancer Genome Consortium (ICGC) datasets and the LUAD sample from Affiliated Hospital of Guangxi Medical University. We also investigated the relation between HOXC6 expression and clinicopathologic indexes. Furthermore, the correlation of immune infiltration, drug responsiveness and HOXC6 were explored.
RESULTS: The upregulated HOXC6 expressions at mRNA and protein levels were found in LUAD tissues compared to the normal lung tissues. Besides, the relatively shorter overall survival time, worse T and N stages, and lower immune scores were found in the high-expression HOXC6 subgroup. Notably, T cells regulatory (Tregs), Macrophages M0, and Plasma cells had the higher infiltration levels in the high-HOXC6 expression subgroup, while NK cells activated, Monocytes, Dendritic cells resting, and Mast cells resting had the lower infiltration levels. In drug sensitivity analysis, we revealed that LUAD patients with high-HOXC6 expression may be more susceptible to Camptothecin, Cytarabine, Docetaxel, Elesclomol, Rapamycin, Sorafinib, Temsirolimus, and Vorinostat.
CONCLUSIONS: Taken together, there is a great potential for HOXC6 to become a prognosis biomarker and contribute to develop treatment strategies for LUAD patients. Further mechanism exploration and drug development for HOXC6 are needed.

BACKGROUND: There is a lack of documentation regarding cytopathology of renal neuroendocrine neoplasms (NENs) due to their rarity.
METHODS: Five cytology cases were gathered from 3 institutes.
RESULTS: Cohort consisted of 4 females and 1 male. Fine needle aspiration biopsy and touch preparation slides of core needle biopsy revealed cellular samples, composed of round, plasmacytoid, or columnar cells. Tumor cells were present in nested, acinar, 3D cluster, and individual cell patterns. Tumor cells in 3 cases exhibited uniformly round to oval small nuclei with inconspicuous nucleoli, finely granular chromatin, and smooth nuclear membranes, whereas 2 other cases showed pleomorphic nuclei with conspicuous nucleoli, nuclear molding, and irregular nuclear membranes. Tumor cells displayed pale or granular cytoplasm, with 1 case showing small vacuoles. Examination of cores and cell blocks demonstrated tumor cells in sheets, nests, or acini. All tumor cells were positive for neuroendocrine immunomarkers. Based on mitotic count, Ki-67 index and morphology, 3 tumors were graded as well-differentiated neuroendocrine tumor (WDNET) (1 grade [G] 3, 1 G2, 1 G1) and 2 as large cell neuroendocrine carcinoma. Deletion of 7q, 10q, and 19q was detected in WDNETs. Two patients with large cell neuroendocrine carcinoma and 1 with WDNET G3 underwent chemotherapy due to aggressiveness, whereas nephrectomy was performed for patients with WDNET G1 and 2 without metastasis.
CONCLUSIONS: Cytopathological characteristics of renal NENs closely resemble those affecting other organs. Despite its rarity, renal NENs should be kept in mind when confronted with morphological resemblances to NENs, to prevent misdiagnosis and inappropriate therapeutic interventions.

BACKGROUND: To investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC.
METHODS: HCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging.
RESULTS: The average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from - 29.03% to 34.78%.
CONCLUSIONS: CTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.

(1) Background: Various cutaneous adverse drug reactions (ADRs) are observed with the implementation of mRNA COVID-19 vaccines. To gain insight into the clinicopathologic features, we analyzed the correlation of histological and clinical data in 48 patients with these ADRs. (2) Methods: Single-center retrospective study in patients with ADRs after mRNA COVID-19 vaccination (mRNA-1273 and BNT162b2 vaccines). (3) Results: Distant generalized ADRs prevailed (91%), often appearing clinically as spongiotic dermatitis or maculopapular exanthema. Histopathological analysis revealed spongiotic changes (46%) and dermal superficial perivascular predominantly lymphocytic infiltrates (17%). Eosinophils were found in 66% of biopsies, neutrophils in 29%, and plasma cells only in 8% of biopsies. Most ADRs occurred after the second vaccine dose (44%). Histologically spongiotic changes were associated with clinical features of spongiotic dermatitis in only 50% of patients and maculopapular exanthema in the remaining patients. ADRs represented an aggravation of preexisting skin disease in 23% of patients. ADRs regressed within 28 days or less in 53% of patients and persisted beyond a month in the remaining patients. (4) Conclusions: Our study demonstrates a diverse spectrum of generalized ADRs, revealing correlations between histology and clinical features but also instances of divergence. Interestingly, in about half of our patients, ADRs were self-limited, whereas ADRs extended beyond a month in the other half.

OBJECTIVE: Cutaneous diseases that disproportionately affect patients with darker pigmentation and their histologic features are historically understudied and undertreated. This review article aims to highlight the key clinical features, histopathology, and diagnostic pearls of several cutaneous diseases that commonly present in patients with darker pigmentation.
METHODS: A literature search was conducted, and a list of cutaneous diseases that frequently affect patients with darker pigmentation was compiled. A group of experts expounded upon those that were most common or misdiagnosed according to scientific evidence and clinical practice.
RESULTS: The diseases were divided into hypopigmented disorders, hyperpigmented disorders, scarring disorders, and alopecic disorders. Within each category, the etiology, clinical features, histopathology, and key histologic differential diagnoses are described and discussed.
CONCLUSIONS: As many clinicians are taught that there are no effective treatment options or that these diseases are considered \"cosmetic\" in nature, patients often do not get a thorough medical workup or skin biopsy. This article aims to decrease the knowledge gap and serve as a resource for anyone involved in the care of patients with these cutaneous conditions.

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UNASSIGNED: Tumor metastases to the retina are a relatively rare occurrence. We report a unique case of retinal metastasis of a systemic malignancy with clinical and histopathologic correlations.
UNASSIGNED: A 62-year-old female with a history of stage IV small cell carcinoma of the lung (SCC, status post chemotherapy and maintenance immunotherapy) presented with hand motions vision and vitreous hemorrhage, status post prior vitrectomy and biopsy that was non-diagnostic. She was found to have unilateral retinal metastatic tumor and underwent a repeat vitrector-assisted biopsy which confirmed the diagnosis. The eye became blind and painful due to recurrent non-clearing vitreous hemorrhage and ghost cell glaucoma and was enucleated. Detailed histopathologic analysis of the globe confirmed small cell carcinoma metastatic to the retina and vitreous cavity and sparing the choroid.
UNASSIGNED: This case demonstrates the importance of maintaining a high index of suspicion for metastasis in patients with a known history of malignancy who present with new vitreoretinal lesions.

Pathologic processes affecting the oral and maxillofacial region include a heterogenous group of diseases with widely variable biologic behaviors. Proper patient management begins with the establishment of an accurate diagnosis, which often relies on histopathologic interpretation of small tissue samples from oral lesions. While confident diagnosis of small oral biopsies can be challenging, an understanding of oral and maxillofacial disease and consistent clinicopathologic correlation can help pathologists recognize inflammatory confounders and overcome common errors in specimen management, including insufficient sample size and non-representative biopsy samples.

It may be challenging to diagnose metastatic prostatic carcinoma (PC). This study focused on clinicopathologic correlation, and pitfalls of cytomorphology and immunostains of metastatic PCs. A total of 146 metastatic PCs including 134 (92%) PC without neuroendocrine differentiation-prostatic adenocarcinoma (PAC) and 12 (8%) with neuroendocrine differentiation (PC-NED) were retrieved. Triplicate tissue microarrays (TMA) of 54 surgically excised PCs were constructed for immunostains. Most cases showed Gleason 4 or 5 patterns. Nine percent of cases did not have a prior history of PC and 7% had 2 or more primary malignancies. PAC metastasized more commonly to lymph nodes (49%), and PC-NED metastasized more commonly to liver (58%). Cytologically, metastatic PCs show acini, cribriform, nest, and solid clusters. Most PACs showed conspicuous or prominent nucleoli. PC-NEDs showed typical cytologic features of low-grade or high-grade neuroendocrine neoplasm, or small cell carcinoma features. PACs could be immunoreactive to CDX2 (25%), CK20 (11%), NKX3.1 (99%), PSA (88%), PSAP (78%), and PSMA (92%). PC-NEDs were immunoreactive to neuroendocrine immunomarkers (CD56 [100%], chromogranin [67%], and synaptophysin [100%]) and p63 (25%), and lost expression of prostate-specific markers (NKX3.1, PSA, PSAP, and PSMA). Both PACs and PC-NEDs might be immunoreactive to CK7 (18% versus 33%), GATA3 (4% versus 0%), PAX8 (2% versus 50%, P < .05), and TTF1 (3% versus 57%, P < .05). It is critical to recognize these cytologic features and abbreviation of immunomarkers of metastatic PCs to avoid misinterpretation as metastatic carcinoma from nonprostate organs and inappropriate treatment. In addition, NED may be seen after hormone and chemoradiation treatment.

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