Neuroendocrine carcinoma of the uterine cervix with extensive pagetoid spread pattern.

There have been no reported cases of neuroendocrine carcinoma (NEC) of the cervix with pagetoid spread (Pag-S). A 44-year-old woman came to our department because of abnormal cytology that persisted immediately after a radical hysterectomy for NEC of the cervix. A mapping biopsy in a large area from the vaginal wall to the vulva revealed that synaptophysin/Ki-67-positive tumor cells were scattered within the epithelium in multiple areas, suggesting a wide Pag-S of NEC. Because tumor cells were found beyond the vaginal wall, the anterior pelvic exenteration was performed. Since we could pathologically confirm the complete resection and no distant metastases were detected, no adjuvant therapy was performed. Four years have passed since the initial treatment without any tumor recurrence. It is known that the prognosis of NEC of the cervix that invades beyond the cervix is poor; however, if there is a Pag-S pattern, a radical surgical treatment can be considered.

A review of 14 cases of perianal Paget's disease: characteristics of anorectal cancer with pagetoid spread.

BACKGROUND: Perianal Paget's disease (PPD) is an intraepithelial invasion of the perianal skin and is frequently associated with underlying anorectal carcinoma. The relatively rare nature of this disease has made it difficult to develop treatment recommendations. This study aims to analyze the clinical and pathological features of perianal Paget's disease (PPD) and to explore rational treatment options and follow-up for this disease. METHODS: The National Cancer Center Hospital database was searched for all cases of perianal Paget's disease diagnosed between 2006 and 2021. In the 14 patients identified, we reviewed the diagnosis, management, and outcomes of adenocarcinoma with pagetoid spread, including suspected or recurrent cases. RESULTS: All 14 cases met the inclusion criteria. The median follow-up period after diagnosis was 4.5 (range, 0.1-13.0) years. Pagetoid spread before initial treatment was suspected in 12 cases (85.7%). Underlying rectal cancer was identified in 6 cases, and no primary tumor was detected in the other 6 cases. Seven patients had recurrent disease, with the median time to recurrence of 34.6 (range, 19.2-81.7) months. The time to the first relapse was 3 months, and that to the second relapse was 6 months. The overall 5-year survival rate was 90.0%. CONCLUSIONS: Endoscopic and radiologic evaluation, as well as immunohistologic examination, should be performed. is to differentiate PPD with and without underlying anorectal carcinoma. The time to first recurrence varies widely, and long-term and regular follow-up for more than 5 years is considered necessary for local recurrence and distant metastasis.

Pulmonary squamous cell carcinoma with a lepidic-pagetoid growth pattern.

We report a rare case of a peripheral squamous cell carcinoma (SCC) of the lung in which most of the tumor displayed a "lepidic" growth pattern. The tumor cells also appeared to grow along the alveolar walls between the overlying pneumocytes and underlying basement membrane, a form reminiscent of the "pagetoid" mode of spread. The neoplastic cells were positive for the squamous markers p63 and p40. TTF-1 and CK7 highlighted residual non-neoplastic pneumocytes, which either covered the lepidic tumor cells or lined pseudoglandular formations created by the filling of alveolar spaces by the tumor. CK7 also stained the tumor cells, albeit focally and weakly, a not uncommon finding in peripheral lung SCC. The tumor cells were negative for TTF-1 (clone 8G7G3/1), but did show focal weak reactivity with the less specific clone SPT24. The invasive area measured 2.5 mm while the overall size of the tumor including the lepidic-pagetoid component was 9.0 mm. Even though the invasive component was < 0.5 cm, the only option according to existing staging criteria was to stage it as pT1a. Since the current staging system does not account for the non-invasive lepidic component of pulmonary SCC, the increasing awareness of this variant may require its inclusion within the classification and pathological staging of lung carcinoma.

Pagetoid involvement of bronchioles by metastatic breast carcinoma.

We report a case of a 36-year-old female with endobronchiolar spread of breast carcinoma in the lung. The patient had recently been diagnosed with invasive ductal breast carcinoma and imaging of the lungs revealed bilateral lung nodules. She then underwent a wedge resection of a lung nodule. The biopsy revealed a subpleural metastatic nodule of invasive ductal carcinoma with an intra-alveolar pattern of spread at its advancing edge. Several smaller foci of intra-alveolar tumor were noted as well as pagetoid spread of tumor cells along a 0.9 mm wide bronchiole. The neoplastic cells were TTF-1 negative, GATA3 positive and ER positive. This is the third reported case of pagetoid spread of metastatic breast carcinoma along the bronchial tree. This case emphasizes the importance of examining not only bronchi but also bronchioles to detect this unusual pattern of spread of metastatic breast carcinoma in lung resection specimens.

Juvenile melanocytic acral nevus: A comparative study between MANIAC and non-MANIAC nevus and its clinicopathological characteristics.

BACKGROUND: Melanocytic acral nevi have a series of distinguishing features, including their location, patient age at onset, clinical progression, and histological findings. In particular, histopathological analysis often reveals a melanocytic acral nevus with intraepidermal ascent of cells (MANIAC nevus), which in some cases can be mistaken for atypia or malignancy. AIM: This study describes the clinicopathological characteristics of acral nevi in patients under 18 years old and contrasts the clinical and histological features between MANIAC vs non-MANIAC nevi. METHODS: This was a retrospective observational study, performed in our department in the decade between January 2007 and January 2017. We included patients younger than 18 years of age who were subjected to the removal of melanocytic acral nevi. RESULTS: A total of 70 patients were studied. 54.2% (38/70) were females and 45.8% (32/70) were males. With regard to the type of nevus, 34 were compound, 27 were junctional, and 9 were predominantly intradermal lesions. We identified a total of 41 MANIAC nevi and 29 non-MANIAC nevi. Statistically significant differences between these two groups were identified in nevus size (larger in MANIAC) and the frequency of compound nevi (higher in the MANIAC group), but not in the remainder of the histological parameters studied.

Clinicopathological features of considerable reduction in androgen receptor expression in sebaceous gland carcinoma of the eyelid.

PURPOSE: This study aimed to evaluate the relationships between androgen receptor (AR) expression and clinicopathologic features of sebaceous gland carcinoma (SGC) of the eyelid. METHODS: AR expression was evaluated via immunohistochemistry analysis of surgically derived samples from 11 patients with SGC of the eyelid. RESULTS: The expression of AR was evident in 9 of 11 patients (82%). We divided patients into high AR (7 patients) and low AR (4 patients: 2 patients with low expression and 2 patients with no expression) groups. The low AR group showed significantly greater progression than the high AR group with regard to T category and exhibited a lower grade of differentiation. CONCLUSION: In patients with SGC of the eyelid, a marked decrease in AR expression may be associated with a poor prognosis. AR may be a prognostic factor and a potential therapeutic target in cases of SGC of the eyelid.

A case of anal canal carcinoma with pagetoid spread that was curatively resected by multiple endoscopic and surgical treatments.

A 57-year-old woman with no significant medical history was referred after a colonoscopy for abdominal distension, which revealed a tumor in the lower rectum. Pre-operative colonoscopy showed the tumor was 12 mm in size, located from the anorectal junction to beyond the dentate line, and was diagnosed as high-grade intramucosal neoplasia or shallow submucosal invasive cancer. Endoscopic submucosal dissection was performed, and the lesion was resected en bloc. Pathological examination revealed moderately differentiated tubular adenocarcinoma with tubulovillous adenoma. The stratified squamous epithelium adjacent to the anal side of the lesion showed pagetoid spread of atypical cells with positive horizontal margins. We referred her to a surgeon for radical treatment. The mucosa surrounding the endoscopic submucosal dissection scar was normal on narrow-band imaging magnification. We marked its oral side endoscopically as the resected boundary. Transanal local excision was performed. The horizontal margins were positive because atypical cells had spread into the stratified squamous epithelium of the anorectal side of the lesion. The patient was followed on an outpatient basis. Sixty days postoperatively, residual tumor growth was observed. The second local resection was performed after mapping biopsy. All resection margins were negative, there was no lymphovascular invasion. One year after surgery, no recurrence was observed. Regarding endoscopic findings, there are no reports of endoscopic findings of the rectal mucosa, or the squamous epithelium of the anus of pagetoid spread. Here, we report a review of perianal Paget's Disease that resulted in difficulties in borderline diagnosis of pagetoid spread, resulting in multiple therapeutic interventions.

Nonmass-forming type anorectal cancer with pagetoid spread: A report of two cases.

Pagetoid spread (PS) of anorectal cancer is relatively rare and associated with poor prognosis. While a primary tumorous lesion is usually obvious in most PS cases, we experienced two cases of nonmass-forming type anorectal cancer with PS. It remains challenging to decide strategies. In both cases, histological findings of a perianal skin biopsy showed proliferation of atypical cells that were positive for cytokeratin (CK) 7, CK20, and caudal type homeobox 2 and negative for Gross cystic disease fluid protein 15, suggesting PS. Abdominoperineal resection (APR) with extensive anal skin resection was performed in both patients. The pathological diagnosis in each was nonmass-forming type anorectal cancer with PS. Neither has experienced recurrence in postoperative courses. Even nonmass-forming type anorectal cancer with PS could have high malignant potentials. APR with lymph nodes dissection and wide skin excision and regular surveillance might be necessary.

[Fluorescence detection to diagnose melanoma : An alternative objective method for dermatohistology]. / Fluoreszenzbasierte Melanomdiagnostik : Eine flankierende objektive Methode zur Dermatohistologie.

BACKGROUND: Dermatohistological assessment is the gold standard in the diagnosis of melanoma. As a subjective method, this depends, among other things, on the expertise of the examiner. AIM: A new objective method of investigation-dermatohistofluoroscopy-aims to improve the diagnostic reliability of melanoma diagnosis. MATERIALS AND METHODS: The ultra-weak spectrally resolved fluorescence of melanin of pigment-bearing skin cells is a reliable indicator of the malignancy of the tissue to be diagnosed. Using a special laser spectroscopic method, this fluorescence can be measured on histological specimen (and also on tissue in vivo and on excidate). RESULTS AND DISCUSSION: Melanocytes from normally pigmented skin, nevomelanocytes from benign and dysplastic nevi, and melanoma cells each show characteristic, different fluorescence spectra. If these cell types are shown spatially resolved in different colors on the preparation to be diagnosed, they give the histologist an objective basis for the diagnosis, even in difficult cases, e.g., the so-called stumbling blocks of melanoma diagnosis such as Spitzoid tumors. Currently, the method can only be used for Fitzpatrick skin types 1 and 2. In addition, a separate second measurement signal at 400 nm can be used to identify tumor breakthrough through the basement membrane. This signal is collagen bound, so it also appears in amelanotic melanomas, to which the method is otherwise inherently inapplicable.

Clinical features of pagetoid spread: Analysis of perianal lesions associated with anal canal adenocarcinoma and perianal primary extramammary Paget disease.

Secondary extramammary Paget disease (s-EMPD) represents anal canal and rectal, bladder, and gynecological cancers, which horizontally extend within the epidermis of the anal and vulvar skin. It is necessary to distinguish this condition from primary extramammary Paget disease (p-EMPD), which occurs primarily in genital and perianal areas. This study aimed to investigate the clinical and histopathological features of these two conditions in the perianal skin and to identify useful features for differentiation. We retrospectively analyzed 16 patients who visited Shinshu University Hospital from 2009 to 2022 and presented with perianal skin lesions and suspected EMPD. Six patients had p-EMPD and 10 had s-EMPD derived from anal canal adenocarcinoma. Regarding clinical features, nine of 10 (90%) of the s-EMPD cases had symmetric skin lesions, whereas all of the p-EMPD cases had asymmetrical lesions (p = 0.0004). Furthermore, assessment of symmetry around the anus showed that s-EMPD had a significantly smaller coefficient of variation than p-EMPD (0.35 and 0.62, respectively; p = 0.048), suggesting that s-EMPD was more symmetric around the anus. The frequency of raised lesions, such as foci or nodules, was nine of 10 (90%) for s-EMPD and one of six (16%) for p-EMPD (p = 0.003). Well-defined tumor borders on the lateral margins were identified in s-EMPD (5/10, 50%); however, they were not identified in p-EMPD (0/6, 0%). The borders tended to be clearer in s-EMPD; however, the difference was not significant (p = 0.078). Based on these findings, we recommend consideration of s-EMPD when anal skin lesions are symmetrical, well-defined, or raised.

A Case of Prostatic Signet-Ring Cell-like Carcinoma with Pagetoid Spread and Intraductal Carcinoma and Long-Term Survival: PD-L1 and Mismatch Repair System Proteins (MMR) Immunohistochemical Evaluation with Systematic Literature Review.

Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like adenocarcinoma (SRCC) is a very rare PA subtype, with around 200 cases reported in the English literature. Histologically, the tumor cells show a vacuole compressing the nucleus to the periphery. Pagetoid spread in acini and ducts is usually related to metastases from urothelial or colorectal carcinomas, less commonly associated with intraductal carcinoma (IC); histologically, the tumor cells grow between the acinar secretory and basal cell layers. To our knowledge, we report the first prostatic SRCC (Gleason score 10, stage pT3b) associated with IC and pagetoid spread to prostatic acini and seminal vesicles. To our systematic literature review (PRISMA guidelines), it is the first tested case for both PD-L1 (<1% of positive tumor cells, clone 22C3) and mismatch repair system proteins (MMR) (MLH1+/MSH2+/PMS2+/MSH6+). We found no SRCC previously tested for MMR, while only four previous cases showed high expression of another PD-L1 clone (28-8). Finally, we discussed the differential diagnoses of prostatic SRCC.

Case report: Recurrent urethral polyps, an atypical presentation of ductal prostate adenocarcinoma.

Prostate ductal adenocarcinoma is a rare subtype of prostate adenocarcinoma which can show aggressive features and have poor response to conventional treatment. Early diagnosis aids in shared patient decision making. We report an atypical presentation of this rare condition where a recurrent urethral polyp which showed pagetoid spread was diagnosed as ductal adenocarcinoma of the prostate, with emphasis on review of prior available histology.

Anal canal adenocarcinoma with pagetoid spread and inguinal lymph node metastasis treated with preoperative chemoradiotherapy: A case report.

Perianal Paget's disease is a rare condition, which is not usually accompanied by cancer. Here, a case of anal canal carcinoma with pagetoid spread and inguinal lymph node metastasis, which exhibited a significant response to preoperative chemoradiotherapy (CRT), is presented. A 58-year-old woman was admitted to The University of Tokyo Hospital with a complaint of discomfort around the anus. Physical examination revealed an erythematous inflamed skin lesion in the perianal region and a tumor of 15 mm in diameter detected on palpation in the left inguinal region, which was diagnosed as metastatic adenocarcinoma by excisional biopsy. Colonoscopy revealed moderately differentiated adenocarcinoma of 15 mm in diameter in the anal canal. Skin biopsy of the perianal region revealed an infiltration of pagetoid cells, which were positive for cytokeratin 7, and negative for cytokeratin 20 and gross cystic disease fluid protein 15. Based on these results, the patient was diagnosed as having anal canal adenocarcinoma with pagetoid spread. The patient received preoperative CRT including the bilateral inguinal region. After CRT, robotic-assisted laparoscopic abdominoperineal resection was performed. The macroscopic findings of the surgical specimen confirmed the formation of a scar as a result of the preoperative CRT. Microscopic examination of the anal tumor revealed no residual carcinoma or lymph node metastasis. In conclusion, this case may suggest the potential applicability of preoperative CRT for the local control of anal canal carcinoma with pagetoid spread.

Perianal Goblet Cell Carcinoid With Pagetoid Spread.

We present a case of perianal goblet cell carcinoid with pagetoid spread. Goblet cell carcinoid, also known as adenocarcinoid tumor, predominantly arises as a primary appendiceal tumor and contains nests of neuroendocrine and mucin-containing cells. When this tumor type is seen in other sites it usually represents a metastasis. We present the case of an 81-year-old woman with a perianal mass. Histologic and immunohistochemical examination following surgical excision showed a goblet cell carcinoid demonstrating pagetoid spread along the perianal squamous mucosa. There was no evidence of a primary appendiceal tumor by history or imaging studies. To our knowledge, this is the first report of a goblet cell carcinoid presenting in this manner. The patient died due to complications of metastatic disease 26 months after initial diagnosis.

Unusual asymptomatic presentation of bladder cancer metastatic to the penis.

Penile metastasis is an extremely rare event and mainly originate from primary pelvic tumor sites such us urinary bladder, gastro-intestinal tract and prostate and more rarely from respiratory system, bone tumors and melanoma. Here we describe the unusual presentation of two bladder urothelial cancer metastatic to the penis with no relevant clinical symptoms. Namely, a 69 years-old man with a warthy lesions of the foreskin and the glans misunderstood for a condylomata that at histological and immunohistochemical analysis showed a bladder urothelial carcinoma; and a 71 years-old man with reddish skin lesion of the glans, a previous history of bladder and urethral carcinoma and histological pagetoid spread of urothelial cancer to the glans. Recurrent bladder urothelial carcinoma is usually a visceral disease that rarely presents as a superficial asymptomatic skin lesion. The two reported cases were asymptomatic superficial penis metastases with a relatively slow growth and a fairy good prognosis after conservative surgical approach. Accurate clinical examination of the penis is mandatory for males with history of bladder cancer.

Recurrence with pagetoid spread arising 17 years after surgery for intramucosal rectal cancer: a case report.

BACKGROUND: Perianal Paget's disease (pPD) is uncommon, with only about 180 cases documented in the literature. Anorectal carcinoma with pagetoid spread is even rarer. CASE PRESENTATION: An 81-year-old woman underwent rectal cancer extirpation with a transanal approach 17 years prior. She has since undergone two reoperations for local rectal cancer recurrence. Then, warts frequently appeared on the vulva on several occasions. Warts appeared on the vulva 1 year ago, which were diagnosed as pPD by biopsy. She underwent perineal tumor resection, and the final histological diagnosis was rectal cancer recurrence with pagetoid spread. The resected stump was positive for cancer cells, and tumor progression was rapid. She underwent additional abdominoperineal resection (Miles' operation) with lymph node dissection. However, disease progression was rapid and she died 7 months after the Miles' operation. CONCLUSIONS: There are some case reports describing anorectal carcinoma with pagetoid spread, however, almost of all those cases were synchronous primary anorectal cancer. Here, we report the first case of metachronous recurrence rectal cancer with pagetoid spread arising 17 years after surgery.

Cervical metastases originating from a primary rectal adenocarcinoma due to a pagetoid spread.

Vulvar Paget disease is a rare skin disorder, considered an in situ adenocarcinoma. It is characterized by intraepithelial Paget cells, of which the origin is unclear. About 75% of cases have a cutaneous origin; the other 25% originate from an intestinal or urological malignancy. We report the first case of retrograde pagetoid spread from a rectal adenocarcinoma to the vulva and cervix. A 66-year-old woman presented with postmenopausal bleeding and a history of Crohn disease. Gynecological workup revealed vulvar and endocervical lesions consisting of Paget cells and adenocarcinoma, respectively. A rectal adenocarcinoma with in situ adenocarcinoma was diagnosed. The surgical specimen demonstrated Paget cells in the squamous epithelium of the anus and vulva. Immunohistochemistry demonstrated an intestinal phenotype of these cells. Genetic testing revealed the same TP53 mutation in tumor cells of the rectal adenocarcinoma and vulvar and endocervical lesions, demonstrating that the Paget cells originated from the same intestinal tumor.

Endobronchial Pagetoid Spread of a Breast Carcinoma Metastatic to the Lung.

A case of endobronchial pagetoid spread of a breast carcinoma metastatic to the lung is described. A 73-year-old woman underwent wedge lung resection after the cytological diagnosis of lung metastasis from ductal invasive breast carcinoma. The breast carcinoma had been surgically removed 6 years previously; at the time of diagnosis it was a T1N0, grade 3 invasive ductal carcinoma, with HER-2 amplification. The lung metastasis measured 1,9 cm and showed the same histology and biological profile of the primary tumor. In addition, numerous neoplastic cells, with large cytoplasm and atypical nuclei, appear to spread along the mucosa of the bronchi adjacent to the metastatic lesion as well as that of the main lobar bronchus, intermingled with the columnar ciliated cells. The neoplastic elements were negative for TTF-1 and strongly HER-2 positive; these features appeared consistent with endobronchial pagetoid spread by the metastatic breast carcinomatous cells.