Mpox Case Presenting With Genital Lesions and Proctitis.

ABSTRACT: Monkeypox (Mpox) is a zoonotic Orthopoxvirus of the Poxviridae family, endemic to Africa. In August 2022, the US government declared it an emergency because of the worldwide spread. Traditionally, Mpox infection spreads through contact with infected animals. However, the 2022 outbreak Centers for Disease Control and Prevention (CDC) data note that 94% of cases had recent male-to-male sexual or close intimate contact, suggesting a novel sexual transmission. In this article, we report a 39-year-old HIV-positive man presenting with a diffuse cutaneous rash, perianal pain, and bloody stool of 2-week duration. A medical history includes intravenous drug use and multiple sexual partners. Physical examination revealed umbilicated, tan-colored, crusted cutaneous papules scattered across the face, trunk, and genital regions. Perianal lesion biopsy showed an acanthotic epidermis with spongiosis, ballooning degeneration of keratinocytes, and the formation of multinucleated syncytial keratinocytes. A dermal superficial/lichenoid mixed inflammatory cell infiltrate with multinucleated giant cells was noted. Perianal lesion polymerase chain reaction (PCR) was positive for Mpox. Colonoscopy revealed a 3-cm circumferential rectal ulcer with gray exudate and necrosis. A rectal ulcer biopsy showed an ulcerated mucosa with acute proctitis and necrosis. There were scattered macrophages with intranuclear inclusion and glassy vacuolization, and Mpox infection was confirmed by immunostaining with a Mpox-specific anti-Vaccinia virus antibody.

Clinicopathologic characterization of cutaneous adult T-cell leukemia/lymphoma: A single tertiary care center experience in the United States.

OBJECTIVES: Adult T-cell leukemia/lymphoma (ATLL) is a rare aggressive T-cell leukemia/lymphoma associated with human T lymphotropic virus type 1 infection. The patients might present with skin rash before, at, or after the diagnosis. The dermatopathologic finding might be diagnostically very challenging. METHODS: We retrospectively identified 110 patients with ATLL at a single institution in a 19-year period, with 19 patients having skin biopsies. Clinical, dermatopathologic, immunophenotypic, and molecular findings were studied. RESULTS: The cohort included 13 skin-first (5 acute, 5 lymphomatous, 2 chronic, 1 smoldering), 6 skin-second (4 acute, 1 lymphomatous, 1 smoldering), and 91 patients without skin biopsy. Some nonphotoprotected areas of body such as the forearm and lower lip were also seen. Skin manifestations included papular (5), erythroderma (1), nodulotumoral (3), plaques (1), patches (1), and a combination of skin rashes (2). Histopathologic findings included large pleomorphic cells, angiocentrism, epidermal infiltration with large Pautrier-like microabscesses, and folliculotropism. Fifteen (78.9%) cases showed CD4+/CD7-/CD25+. Next-generation sequencing study was conducted on 5 patients using either blood or bone marrow samples, revealing multiple genetic mutations across multiple signaling pathways. CONCLUSIONS: Pleomorphic large, atypical cells with CD4+/CD25+/CD7- immunophenotype from a non-"bathing trunk" location, especially in a patient from endemic regions, raise suspicion for ATLL. T-cell receptor gene rearrangement is almost always positive, and the neoplasm usually demonstrates multiple mutations by next-generation sequencing study.

Melanoma Mimicker: Pigmented Mammary Paget Disease in a Man.

ABSTRACT: Male breast cancer comprises less than 1% of all breast cancer cases. Mammary Paget disease (MPD) represents a subset of breast cancer that presents with skin changes of the nipple and areola, and is frequently misdiagnosed clinically due to similarities with other disease states, leading to an average delay in diagnosis of 1 month to 2 years. Pigmented mammary Paget disease (PMPD) is an uncommon variant of MPD that clinically and histologically resembles malignant melanoma. Due to variable immunohistochemical staining patterns, analysis can be challenging and often requires interpretation of panels for accurate diagnosis. We present a rare case of PMPD in a male, originally diagnosed both clinically and histologically as malignant melanoma, to highlight the diagnostic challenges that this entity presents, and to review staining patterns which may be useful in its diagnosis.

Acute generalized exanthematous pustulosis associated with clindamycin in a patient with Hailey-Hailey disease.

A 61-year-old African-American female with moderately controlled Hailey-Hailey disease (HHD) presents to the emergency department with a rash and fever. One day prior to her presentation, she was started on oral clindamycin for a tooth extraction procedure. Her physical examination shows diffuse erythema on the trunk and extremities with multiple nonfollicular pustules. A punch biopsy of her upper extremity revealed intraepidermal acantholysis, neutrophilic spongiosis, and subcorneal pustules. The perivascular and interstitial superficial dermal infiltrate is mixed and composed of predominantly neutrophils, with lymphocytes and rare eosinophils. These findings suggest a superimposed acute generalized exanthematous pustulosis (AGEP) in the background of HHD. AGEP is a potentially severe cutaneous condition characterized by the abrupt onset of numerous nonfollicular pustules in a background of pruritic edematous erythroderma. To date, only two case reports have described AGEP in patients with HHD. Early diagnosis of AGEP is essential to initiate prompt and aggressive systemic therapy, prompt medication cessation, close monitoring for end-organ damage, and improve overall morbidity and mortality.

Isolated trigeminal neuralgia: An early weird presentation of carcinoma breast.

We report an interesting case of a 52-year-old postmenopausal female who presented with a 2-month history of headache, tingling sensation, and sharp shooting pain over the left face, followed by left facial paresthesia with pain over the maxillary region. Magnetic resonance imaging scan revealed presence of enplaque altered signal intensity soft-tissue lesion along the left 5th nerve from its origin at pons, and positron emission tomography with concurrent computed tomography showed a 2.9 cm × 2.6 cm intensely 18F-fluorodeoxyglucose-avid breast mass, in the upper outer quadrant of the right breast. Core-needle biopsy revealed infiltrating ductal carcinoma. Her estrogen receptor, progesterone receptor, and Her2-neu analysis suggested triple-negative breast cancer. She was managed with cranial radiotherapy and palliative chemotherapy. The patient responded very well to radiotherapy and chemotherapy with complete improvement in her neurological symptoms and now she is under regular follow-up for chemotherapy for 8 months without any subjective or objective progression of the disease. Isolated cranial neuropathy may be an early harbinger of metastatic breast cancer, so we should search for the primary malignancy. TNBC is associated with early central nervous system metastasis because of heterogeneity in the biology of the disease. Whole-brain radiotherapy and palliative chemotherapy are the best available treatment modalities.

Clinical, pathologic, and molecular analyses of superficial low-grade fibromyxoid sarcoma in two young patients: A rare and deceptive mimic of benignancy.

Low-grade fibromyxoid sarcoma (LGFMS) is a histopathologically deceptive soft tissue neoplasm with bland cytology, which is typically encountered in deep soft tissue of adults. We report two cases of superficial LGFMS in young patients (16 and 21 years old, respectively), which were difficult to diagnose on histopathologic and clinical findings alone. LGFMS commonly mimics benign neoplasms such as cellular neurothekeoma, fibromatosis, neurofibroma, and perineurioma. Malignancies included in the differential diagnosis are soft tissue neoplasms such as dermatofibrosarcoma protuberans and myxofibrosarcoma. A high degree of reported variation in pattern and cellularity among LGFMS further complicates the diagnosis. Careful examination and appropriate immunohistochemistry panels including MUC4 are essential for narrowing the differential diagnosis. Molecular studies for possible FUS translocation can confirm the diagnosis of LGFMS. Sufficient sampling and workup of these lesions are critical, especially in younger patients. Young age and superficial presentation can easily sway dermatopathologists/dermatologists toward an incorrect diagnosis of benignancy.

TERT gene rearrangement in chordomas and comparison to other TERT-rearranged solid tumors.

Chordomas are rare, slow-growing neoplasms thought to arise from the foetal notochord remnant. A limited number of studies that examined the mutational profiles in chordomas identified potential driver mutations, including duplication in the TBXT gene (encoding brachyury), mutations in the PI3K/AKT signaling pathway, and loss of the CDKN2A gene. Most chordomas remain without clear driver mutations, and no fusion genes have been identified thus far. We discovered a novel TERT in-frame fusion involving RPH3AL (exon 5) and TERT (exon 2) in the index chordoma case. We screened a discovery cohort of 18 additional chordoma cases for TERT gene rearrangement by FISH, in which TERT rearrangement was identified in one additional case. In our independent, validation cohort of 36 chordomas, no TERT rearrangement was observed by FISH. Immunohistochemistry optimized for nuclear TERT expression showed at least focal TERT expression in 40/55 (72.7%) chordomas. Selected cases underwent molecular genetic profiling, which showed low tumor mutational burdens (TMBs) without obvious driver oncogenic mutations. We next examined a cohort of 1,913 solid tumor patients for TERT rearrangements, and TERT fusions involving exon 2 were observed in 7/1,913 (0.4%) cases. The seven tumors comprised five glial tumors, and two poorly differentiated carcinomas. In contrast to chordomas, the other TERT-rearranged tumors were notable for higher TMBs, frequent TP53 mutations (6/7) and presence of other driver oncogenic mutations, including a concurrent fusion (TRIM24-MET). In conclusion, TERT gene rearrangements are seen in a small subset (2/55, 3.6%) of chordomas. In contrast to other TERT-rearranged tumors, where the TERT rearrangements are likely passenger events, the possibility that TERT protein overexpression representing a key event in chordoma tumorigenesis is left open.

Report of a Rare Case of Spindle Cell Ameloblastic Carcinoma and the Diagnostic Utility of Immunohistochemistry.

Ameloblastic carcinoma is a rare aggressive malignant epithelial odontogenic tumor. The spindle cell variant of ameloblastic carcinoma (SCAC) is exceedingly rare with 15 cases of SCAC having been reported. Therefore, because of the paucity of cases in literature related to SCAC, the biological behavior of the entity has not been well evaluated. Herein the authors report a case of incidentally diagnosed SCAC in a 20-year-old woman identified on imaging as part of the evaluation of a work-related facial injury. Histologically, the tumor had background of cystic ameloblastoma with areas of dense hypercellular spindle cells with short-to-long intersecting fascicles and occasional herringbone pattern intermixed with solid epithelial nests. Both the epithelial and spindle cells were positive for cytokeratin including cytokeratin 19, D2-40, and transducin-like enhancer of split proteins-1 immunohistochemical stains. The patient was followed for 18 months with no evidence of recurrence or metastasis. To the knowledge this is a first case of reporting D2-40 positivity in spindle ameloblastic carcinoma and this immunostain could be used as helpful marker to diagnose this entity.

Metastatic Melanoma With Features of Desmoplastic Melanoma in a Patient With Primary Cutaneous Superficial Spreading Melanoma With Epithelioid Features.

ABSTRACT: The synchronous incidence of 2 different subtypes of melanoma is very rare. Desmoplastic melanoma (DM) can be a diagnostic challenge because of its frequent appearance as a dermal banal spindle cell proliferation. We present a case of a 30-year-old man who developed an irregular, purple, tender plaque measuring 2.5 cm on the right pretibial region. Wide excision of the right leg lesion showed superficial spreading melanoma with epithelioid cells and no spindle cell component. Sentinel lymph node (SLN) biopsy showed an atypical melanocytic proliferation involving one inguinal lymph node with subcapsular and intraparenchymal components. There were spindled tumor cells in lymph node capsule with hyperchromatic nuclei, which were nested within desmoplastic stroma, and were S100- and SOX10-positive and MART1- and HMB-45 negative; in addition to epithelioid tumor cells, which were S100-, SOX10-, and MART1-positive. Multiple discontinuous foci, subcapsular atypical melanocytes, and extracapsular extension helped in excluding capsular nevus. These findings were consistent with DM. Herein, we present an unusual case of primary cutaneous superficial spreading melanoma of the right leg with a predominantly epithelioid morphology that developed metastases to the SLN. The metastasis exhibited divergent differentiation, including both epithelioid morphology identical to the primary, but with additional features of DM that were nonoverlapping with the primary lesion.

A case of tumor-to-tumor metastasis of cutaneous malignant melanoma.

We report a case of tumor-to-tumor metastasis of a cutaneous malignant melanoma to a synchronous thyroid Hurthle cell carcinoma. A 42-year-old male underwent a biopsy of right inguinal lymphadenopathy which showed metastatic melanoma. The primary lesion was identified on his right posterior leg, and staging workup discovered a synchronous left thyroid lobe nodule concerning for a follicular neoplasm. He underwent excision of the primary melanoma, right inguinal lymphadenectomy, and total thyroidectomy. The resected thyroid contained a 6.6-cm, well-encapsulated left-sided nodule, red-brown in color and homogenous in consistency, with areas of focal hemorrhage and no grossly identifiable calcification. Microscopically, large tumor cells with distinct cell borders were present, with deeply eosinophilic and granular cytoplasm, large nuclei with prominent nucleoli, and loss of polarity consistent with oncocytes. A microscopic single focus of vascular invasion was identified, and a diagnosis of angioinvasive Hurthle cell carcinoma was made. Within the Hurthle cell carcinoma, multiple deposits of metastatic melanoma were seen. These findings were indicative of tumor-to-tumor metastasis of the cutaneous melanoma to the angioinvasive Hurthle cell carcinoma. Our findings show the ability of melanoma to metastasize to a pre-existing neoplasm.

Proximal Descending Thoracic Aortic Pseudoaneurysm Secondary to Pott's Spine.

Tuberculous pseudoaneurysm of the descending thoracic aorta is quite rare, life-threatening, and fatal if not diagnosed in time. This lesion exposes patients to a very high risk of unpredictable rupture. We describe a case of tuberculous pseudoaneurysm of the aorta in association with tuberculosis of the spine (Pott's spine). A 73-year-old man presented with a 2-month history of back pain. Chest roentgenography and contrast-enhanced computed tomography showed a descending thoracic aortic pseudoaneurysm with destruction of the fourth and fifth thoracic vertebrae (T4-T5). We suspected that the pseudoaneurysm was due to direct extension of tuberculous vertebral osteomyelitis. The patient was managed with antituberculous chemotherapy. The post-antitubercular therapy course was uneventful and he remained well 12 months after completion of treatment.

Urethral involvement is associated with higher mortality and local recurrence in vulvar melanoma: a single institutional experience.

Vulvar malignant melanoma (VMM), although uncommon, comprises 5-10% of all vulvar malignancies. Local control is notoriously poor in VMM with recurrence rates of 30-50% compared with approximately 3% in cutaneous melanomas. We studied clinicopathologic features of 37 women with VMM, after reviewing three decades of clinical follow-up data in our institutional databases. Most patients were Caucasian (n = 35) with an average age at diagnosis of 60.6 years (range 23-83). The most common subtype was mucosal lentiginous melanoma (n = 25). We compared Kaplan-Meier survival curves of 31 patients defined by clinical and microscopic attributes using exact log-rank tests. Younger patients at diagnosis (23-64 years), those with thin melanomas (≤1 mm), and those with Clark's level II or III tumors had better 5-year survival rates than older patients (65-83 years) and those with thick melanomas (>1 mm) and those with Clark's level IV or V (P ≤ 0.05), respectively, by exact log-rank test. Local recurrence of melanoma occurred in 15 patients. Nine patients (24%) had eventual urethral involvement by malignant melanoma, and this feature was associated with significantly shorter survival (P = 0.036). Patients with urethral involvement had shorter median time to death and worse 5-year survival rates. Given that spread to the urethra is common in VMM and urethral recurrence is also associated with mortality, pathology excision specimens should be carefully reviewed with attention to urethral involvement as a potentially important prognostic factor.

Intraconal Metastasis Leading to Diagnosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the commontumor of the liver and the third most common cause of cancer-related mortality worldwide. Patients with HCC may have metastasis to different sites. Intrahepatic and extrahepatic metastases are found in (~50-75%). Lung and regional lymph nodes are the most commonly involved sites. Metastasis to bone, skin, and adrenal glands are rare. Orbit metastasis and intracranial invasion are extremely rare. We are presenting a case of HCC that metastasized to the orbital cavity. The patient presented with progressive proptosis of the eyeball with retrobulbar and intracranial invasion and involvement of the sub-scalp region. Based on the imaging findings, it was initially misdiagnosed as meningioma; however, histopathological examination of the biopsy specimen resulted in a definitive diagnosis of HCC metastasis. The present case reveals that the alternative diagnosis of metastasis must be considered when diagnosing retrobulbar lesions in patients with HCC.

Pregnancy Outcomes in Chronic Myeloid Leukemia: A Single Center Experience.

PURPOSE: The aim of the current work was to report the effect of imatinib on pregnancy in patients with chronic myeloid leukemia (CML). METHODS: Data were collected between January 1998 and December 2014. One hundred four patients met inclusion criteria, and we report the results of 104 pregnancies-conceived by the participant or partner-while being on imatinib therapy for CML. RESULTS: Fifty-eight patients were male and 46 were female. Eighty-three patients, 20 patients, and one patient were had CML in the chronic phase, accelerated phase, or blast phase, respectively. Of 46 female patients, 21 underwent abortion (spontaneous, n = 36.9; elective termination, n = 8.6%). In the case of full-term pregnancy in the female partners of male patients with CML, all outcomes were uneventful. Of 46 female patients, 25 had full-term pregnancy outcomes. During the pre-imatinib era (total n = 6), patients were treated with hydroxyurea, interferon-alpha, and therapeutic leukapheresis. A total 10 of 19 pregnant patients continued on imatinib until their delivery and experienced the following outcomes: normal full-term deliveries (n = 7), preterm delivery (n = 1), omphalocele (n = 1), and craniosynostosis (n = 1). Of those who discontinued imatinib after counseling (n = 9), eight patients had full-term normal delivery, of which two patients required leukapheresis and one patient expired. All patients who continued on imatinib while pregnant were in complete cytogenetic response and major molecular response (MMR) before pregnancy, during pregnancy, and postpregnancy. Of nine patients who discontinued imatinib, two lost MMR during the third trimester and all of these patients were in complete cytogenetic response and MMR before pregnancy. CONCLUSION: It is clear that there is no standard of care for the best treatment of CML in the case of pregnancy. Interferon and/or leukapheresis will be included as treatment options. Patients can have normal pregnancies even with the administration of imatinib at the risk of congenital anomalies, intervention for which can be done after birth.

Exceptional Responder to Immunotherapy: A Rare Case of Post-HSCT DLBCL Relapse Responding to Nivolumab.

Immunotherapy is the treatment that either boosts the patient's immune system or uses human-made versions of the normal parts of the immune system to kill lymphoma cells or slow their growth. A forty-eight-year-old lady with neck nodes, axillary nodes, weight loss and fever diagnosed to have Diffuse Large B-Cell Lymphoma (DLBCL) in December 2009 was treated with 6 cycles of R-CHOP, and her treatment was completed in May 2010. After 2 years in July 2012, the patient developed similar symptoms and received salvage chemotherapy with R-DHAP, and her treatment was completed in January 2013. After one and a half years, in August 2014, the patient again had relapsed DLBCL. She was treated with R-ICE 4-cycles and rendered disease-free following allogeneic HSCT in June 2015. But in December 2016, the patient again developed isolated axillary lymphadenopathy and relapsed DLBCL was confirmed by HPR and IHC. This time, the patient was unwilling to go on chemotherapy, but after counselling about the new drug, Nivolumab, she became convinced, and her treatment was started with 3mg per kg every 2 weeks. After 4 cycles, she had a complete response and is now being treated with the same treatment without any symptoms of the disease or any adverse drug reactions. Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B- cell lymphomas. Additional studies are ongoing to learn more about the use of Nivolumab in these diseases.

An alternative approach to establishing unbiased colorectal cancer risk estimation in Lynch syndrome.

PURPOSE: Biallelic pathogenic variants in the mismatch repair (MMR) genes cause a recessive childhood cancer predisposition syndrome known as constitutional mismatch repair deficiency (CMMRD). Family members with a heterozygous MMR variant have Lynch syndrome. We aimed at estimating cancer risk in these heterozygous carriers as a novel approach to avoid complicated statistical methods to correct for ascertainment bias. METHODS: Cumulative colorectal cancer incidence was estimated in a cohort of PMS2- and MSH6-associated families, ascertained by the CMMRD phenotype of the index, by using mutation probabilities based on kinship coefficients as analytical weights in a proportional hazard regression on the cause-specific hazards. Confidence intervals (CIs) were obtained by bootstrapping at the family level. RESULTS: The estimated cumulative colorectal cancer risk at age 70 years for heterozygous PMS2 variant carriers was 8.7% (95% CI 4.3-12.7%) for both sexes combined, and 9.9% (95% CI 4.9-15.3%) for men and 5.9% (95% CI 1.6-11.1%) for women separately. For heterozygous MSH6 variant carriers these estimates are 11.8% (95% CI 4.5-22.7%) for both sexes combined, 10.0% (95% CI 1.83-24.5%) for men and 11.7% (95% CI 2.10-26.5%) for women. CONCLUSION: Our findings are consistent with previous reports that used more complex statistical methods to correct for ascertainment bias. These results underline the need for MMR gene-specific surveillance protocols for Lynch syndrome.